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PubMed: 21482353

Title
Neural systems governed by nicotinic acetylcholine receptors: emerging hypotheses.
Journal
Neuron
Volume
70
Issue
None
Pages
20-33
Date
2011-04-14
Authors
Miwa JM | Freedman R | Lester HA

Evidence f1613cef86
JSON

The neurons release additional GABA, activating presynaptic GABAB receptors on the excitatory inputs to pyramidal neurons, which diminish the release of glutamate onto the pyramidal neurons (Figure 2)

a(CHEBI:"gamma-aminobutyric acid") increases act(p(HGNC:GABBR1)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Pyramidal Cells

a(CHEBI:"gamma-aminobutyric acid") increases act(p(HGNC:GABBR2)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Pyramidal Cells

a(CHEBI:"gamma-aminobutyric acid") decreases tloc(a(CHEBI:"glutamate(2-)"), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Pyramidal Cells

a(MESH:Neurons) increases tloc(a(CHEBI:"gamma-aminobutyric acid"), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Appears in Networks:

Evidence 9f68c9c8cd
JSON

We now realize that acetylcholine liberated from cholinergic nerve terminals often activates both nAChRs and muscarinic receptors

a(CHEBI:acetylcholine) increases act(p(FPLX:CHRN)) View Subject | View Object

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a(CHEBI:acetylcholine) increases act(p(FPLX:CHRM)) View Subject | View Object

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Evidence a29f7cc18b
JSON

A possible candidate is choline, which, in addition to its other development roles, activates alpha7 nAChRs at levels several fold higher than acetylcholine

a(CHEBI:acetylcholine) increases act(a(HBP:"alpha-7-containing nAChR")) View Subject | View Object

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a(CHEBI:choline) increases act(a(HBP:"alpha-7-containing nAChR")) View Subject | View Object

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Evidence 378f77ce09
JSON

As we will see below, the mystery of somatodendritic nAChRs can also be resolved by the sensitivity of alpha7 nAChRs to constant levels of another agonist, choline

a(CHEBI:choline) increases act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

Appears in Networks:

Evidence 3f5933de95
JSON

A major subtype in the brain is alpha4beta2; the (alpha42beta23) stoichiometry exhibits at least 10-fold-higher sensitivity than (alpha43beta22), so that only the former has the high sensitivity (HS) that allows activation at nicotine concentrations in the 0.1–1 mM range, produced by moderate tobacco use and by the various nicotine replacement therapies

a(CHEBI:nicotine) increases complex(p(HGNC:CHRNA4), p(HGNC:CHRNA4), p(HGNC:CHRNB2), p(HGNC:CHRNB2), p(HGNC:CHRNB2)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence 5517979436
JSON

alpha7 nAChRs also respond to nicotine concentrations roughly an order of magnitude higher than alpha42beta23, and alpha7 nAChRs have high Ca2+ permeability resembling that of NMDA receptors

a(CHEBI:nicotine) increases act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

Appears in Networks:

act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) association bp(GO:"calcium ion transport") View Subject | View Object

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bp(GO:"calcium ion transport") association act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

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Evidence d01f1d8e84
JSON

While it is not yet possible to know precisely how well a7 nAChRs are activated by smoked nicotine, one can reasonably hypothesize that the patients’ higher dose of nicotine activates alpha7 nAChRs (Adler et al., 1993; Papke and Thinschmidt, 1998; Royal College of Physicians, 2007)

a(CHEBI:nicotine) increases act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

Evidence 6c2b40b817
JSON

Evidence thus far indicates that the lynx family is regulated in response to relatively strong perturbations: downregulation in NKCC1 knockout mice (Pfeffer et al., 2009), in adenylyl cyclase mutant mice (Wieczorek et al., 2010), and by alpha7 nAChR blockade (Hruska et al., 2009), whereas it is upregulated at the close of the critical period in the visual cortex, and by nicotine in the lung (Sekhon et al., 2005)

a(CHEBI:nicotine) increases act(p(MGI:Lynx1)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Lung

act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) increases act(p(MGI:Lynx1)) View Subject | View Object

Appears in Networks:

p(FPLX:ADCY, var("?")) decreases act(p(MGI:Lynx1)) View Subject | View Object

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p(MGI:Slc12a2) increases act(p(MGI:Lynx1)) View Subject | View Object

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Evidence 58c896b1b1
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Nicotine both activates and desensitizes nAChRs in midbrain dopaminergic neurons (Brodie, 1991; Pidoplichko et al., 1997), and the pleasurable effects associated with nicotine intake occur in large part via the mesolimbic dopaminergic reward system (Corrigall et al., 1992; Koob and Volkow,2010)

a(CHEBI:nicotine) increases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons

Evidence 71be6fab4e
JSON

This puzzle does not yet have a complete answer, but it is clear that chronic nicotine increases the number of nAChRs themselves (Marks et al., 1983; Schwartz and Kellar, 1983)

a(CHEBI:nicotine) increases p(FPLX:CHRN) View Subject | View Object

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Evidence efdf3d5538
JSON

At the level of whole brain, chronic nicotine causes selective upregulation of nAChRs among major brain regions. Upregulation occurs in cortex, midbrain, and hypothalamus, but not in thalamus or cerebellum (Pauly et al., 1991; Marks et al., 1992; Nguyen et al., 2003; Nashmi et al., 2007; Doura et al., 2008)

a(CHEBI:nicotine) increases p(FPLX:CHRN) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hypothalamus
MeSH
Mesencephalon

a(CHEBI:nicotine) causesNoChange p(FPLX:CHRN) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebellum
MeSH
Thalamus

Evidence dc202620fd
JSON

However, it is not known whether the nicotine-enhanced cognitive performance exceeds the level that would occur if the person had never begun to smoke, or after remaining abstinent for one year (the usual criterion for successful smoking cessation) (Levin et al., 2006)

a(CHEBI:nicotine) increases bp(GO:cognition) View Subject | View Object

Appears in Networks:

Evidence 466049797e
JSON

Chronic or acute nicotine enhances LTP in several regions of hippocampus, especially dentate gyrus (Nashmi et al., 2007; TangandDani, 2009;Pentonet al., 2011)

a(CHEBI:nicotine) increases bp(GO:"long-term synaptic potentiation") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dentate Gyrus
MeSH
Hippocampus

Evidence 3ba87c5ed5
JSON

For instance, dopamine increases in the extended amygdala during stress, fear, and nicotine withdrawal (Inglis and Moghaddam, 1999; Pape, 2005; Grace et al., 2007; Gallagher et al., 2008; Koob, 2009; Marcinkiewcz et al., 2009)

a(CHEBI:nicotine) decreases a(CHEBI:dopamine) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Amygdala

bp(MESH:"Stress, Physiological") increases a(CHEBI:dopamine) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Amygdala

path(MESH:Fear) increases a(CHEBI:dopamine) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Amygdala

Evidence a78d6ede5e
JSON

Chronic nicotine upregulates alpha4* nAChRs in dopaminergic presynaptic terminals, apparently leading to increased resting dopamine release from those terminals

a(CHEBI:nicotine) increases tloc(a(CHEBI:dopamine), fromLoc(MESH:"Presynaptic Terminals"), toLoc(GO:"extracellular region")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Presynaptic Terminals

a(CHEBI:nicotine) increases act(a(HBP:"alpha-4-containing nAChR")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Presynaptic Terminals

Evidence 47d5299758
JSON

In the medial perforant path, which mainly arises from layer II stellate cells, chronic nicotine upregulates alpha4beta2* nAChRs

a(CHEBI:nicotine) increases act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dentate Gyrus
MeSH
Entorhinal Cortex

Evidence 4ef36d539e
JSON

In midbrain, chronic nicotine treatment elicits a general increase in alpha4beta2* nAChRs in GABAergic neurons, but only in axon terminals of DA neurons

a(CHEBI:nicotine) increases act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
GABAergic Neurons
MeSH
Mesencephalon

Evidence c528b86f16
JSON

Because alpha4beta2 nAChRs are the most susceptible to nicotine-induced upregulation, the data again seem consistent with the idea that selective upregulation of alpha4beta2 nAChRs underlies nicotine dependence

a(CHEBI:nicotine) increases act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

Appears in Networks:

path(MESH:"Tobacco Use Disorder") increases act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

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Evidence 1c271dfddc
JSON

The upregulation of alpha4beta2* nAChRs by chronic nicotine treatment has been replicated many times in numerous systems—transfected cell lines, neurons in culture, brain slices, and smokers’ brains (Albuquerque et al., 2009; Fu et al., 2009; Lester et al., 2009; Srinivasan et al., 2011

a(CHEBI:nicotine) increases act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

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Evidence e69ea3b378
JSON

(3) Nicotine activates alpha4beta2 nAChRs ~400-fold more effectively than it activates muscle-type nAChRs, because of cation-π and H-bond interactions at the agonist binding site (Xiu et al., 2009)

a(CHEBI:nicotine) increases act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

Appears in Networks:

Evidence 50fbe1c084
JSON

While chronic nicotine does not change the abundance or function of alpha4* nAChRs in the somata of substantia nigra pars compacta dopaminergic neurons, it does suppress baseline firing rates of these DA neurons.

a(CHEBI:nicotine) causesNoChange a(HBP:"alpha-4-containing nAChR") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Pars Compacta

a(CHEBI:nicotine) decreases act(a(MESH:"Dopaminergic Neurons")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Pars Compacta

Evidence 820db1d971
JSON

These contrasting effects on GABA and DA neurons are due to upregulated alpha4* nAChR responses in GABA neurons, at both somata and synaptic terminals

a(CHEBI:nicotine) increases act(a(HBP:"alpha-4-containing nAChR")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
GABAergic Neurons

Evidence 3b1f2b7e31
JSON

The chaperoning of nAChRs by nicotine enhances the export of alpha4beta2 nAChRs from the endoplasmic reticulum (ER), and this leads to a general increase in ER exit sites (Srinivasan et al., 2011)

a(CHEBI:nicotine) increases tloc(a(HBP:"alpha-4-containing nAChR"), fromLoc(GO:"endoplasmic reticulum"), toLoc(GO:"extracellular region")) View Subject | View Object

Appears in Networks:

Evidence 137711f73f
JSON

In mice exposed to chronic nicotine, GABA neurons in substantia nigra pars reticulata have increased baseline firing rates, both in brain slices and in anesthetized animals

a(CHEBI:nicotine) increases act(a(MESH:"GABAergic Neurons")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Pars Reticulata

Evidence 8a16c40d92
JSON

ADNFLE patients who use a nicotine patch or tobacco have fewer seizures (Willoughby et al., 2003; Brodtkorb and Picard, 2006)

a(CHEBI:nicotine) decreases path(HBP:"Autosomal Dominant Nocturnal Frontal Lobe Epilepsy") View Subject | View Object

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Evidence b591bca93e
JSON

Variants in the gene for phosphatidylethanolamine methyl transferase, which synthesizes phosphatidylcholine and thus provides a source of choline, are also associated with choline deficiency and with schizophrenia

a(CHEBI:phosphatidylcholine) increases a(CHEBI:choline) View Subject | View Object

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p(HGNC:PEMT) increases a(CHEBI:phosphatidylcholine) View Subject | View Object

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p(HGNC:PEMT, var("?")) association path(MESH:"Choline Deficiency") View Subject | View Object

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p(HGNC:PEMT, var("?")) association path(MESH:Schizophrenia) View Subject | View Object

Appears in Networks:

path(MESH:"Choline Deficiency") association p(HGNC:PEMT, var("?")) View Subject | View Object

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path(MESH:Schizophrenia) association p(HGNC:PEMT, var("?")) View Subject | View Object

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Evidence 98bb132cb3
JSON

3-(2,4 dimethoxy)-benzylidene-anabaseine, derived from an alkaloid produced by nemertine worms, is a partial agonist at alpha7 nAChRs

a(HBP:"GTS-21") increases act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

Evidence 9f2e1c68c5
JSON

It improves sensory inhibition in schizophrenics and also moderately improves their neuropsychological deficits in attention (Olincy et al., 2006)

a(HBP:"GTS-21") increases path(MESH:Attention) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

a(HBP:"GTS-21") increases bp(GO:"sensory processing") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

Evidence 637e8299d7
JSON

Clinical ratings of their negative symptoms, particularly anhedonia (absence of a sense of pleasure) and alogia (poverty of content in their speech), also improve during treatment

a(HBP:"GTS-21") decreases path(MESH:Anhedonia) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

a(HBP:"GTS-21") decreases path(MESH:Aphasia) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

Evidence 38ccc613aa
JSON

In rodents and humans, the hippocampus is importantly implicated in cognitive sensitization, and alpha4beta2* nAChRs play key roles (Levin et al., 2006; Davis and Gould, 2009)

a(HBP:"alpha-4 beta-2 nAChR") positiveCorrelation bp(GO:cognition) View Subject | View Object

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bp(GO:cognition) positiveCorrelation a(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

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Evidence 48a7f0d0ef
JSON

In the midbrain, both DA neurons (in substantia nigra pars compacta and ventral tegmental area [VTA]) and GABAergic neurons (in substantia nigra pars reticulata and VTA) express high levels of alpha4beta2* nAChRs on their somata, but only GABAergic neurons display somatic upregulation (Nashmi et al., 2007; Xiao et al., 2009)

a(HBP:"alpha-4 beta-2 nAChR") positiveCorrelation a(MESH:"Dopaminergic Neurons") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Mesencephalon
MeSH
Pars Compacta
MeSH
Ventral Tegmental Area

a(HBP:"alpha-4 beta-2 nAChR") positiveCorrelation a(MESH:"GABAergic Neurons") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Mesencephalon
MeSH
Pars Reticulata
MeSH
Ventral Tegmental Area

a(MESH:"Dopaminergic Neurons") positiveCorrelation a(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Mesencephalon
MeSH
Pars Compacta
MeSH
Ventral Tegmental Area

a(MESH:"GABAergic Neurons") positiveCorrelation a(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Mesencephalon
MeSH
Pars Reticulata
MeSH
Ventral Tegmental Area

Evidence 64dd958289
JSON

One important role for alpha7 nAChRs, in conjunction with alpha3-containing nAChRs, is the induction of the KCC2 chloride transporter in pyramidal neurons (Liu et al., 2006)

a(HBP:"alpha-7-containing nAChR") increases p(HGNC:SLC12A5) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Pyramidal Cells

Evidence 7878eef85e
JSON

A specific role of alpha7 nAChRs was demonstrated by failure of the induction of KCC2 by treatment with alpha7 nAChR antagonists and in a7 KO mice (Zhang and Berg, 2007)

a(HBP:"alpha-7-containing nAChR") increases p(HGNC:SLC12A5) View Subject | View Object

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Evidence d80b2647f4
JSON

alpha7 nAChRs are involved in the macrophage and placental cytokine response, which may be an additional role for genetic variants in these receptors in the pathogenesis of schizophrenia (Wang et al., 2003)

a(HBP:"alpha-7-containing nAChR") association bp(GO:"macrophage activation") View Subject | View Object

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a(HBP:"alpha-7-containing nAChR") association bp(GO:"response to cytokine") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Placenta

bp(GO:"macrophage activation") association a(HBP:"alpha-7-containing nAChR") View Subject | View Object

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bp(GO:"response to cytokine") association a(HBP:"alpha-7-containing nAChR") View Subject | View Object

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Annotations
MeSH
Placenta

Evidence 1a2a0bc336
JSON

First, postmortem studies of the hippocampus and thalamus show diminished labeling of putative inhibitory neurons by alpha-bungarotoxin, an antagonist of alpha7 nAChRs (Court et al., 1999)

a(HBP:"alpha-Bungarotoxin") increases act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

a(MESH:"alpha7 Nicotinic Acetylcholine Receptor") increases a(HP:"inhibitory interneuron") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

Evidence 0b278efc7d
JSON

alpha7 nAChRs on inhibitory interneurons throughout the hippocampus and presynaptic alpha7 nAChRs on mossy fiber terminals in the dentate gyrus participate in the control of sensory response in the hippocampus (Gray et al., 1996; Alkondon et al., 1999

a(HP:"inhibitory interneuron") regulates bp(GO:"sensory processing") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dentate Gyrus
MeSH
Hippocampus

a(MESH:"alpha7 Nicotinic Acetylcholine Receptor") regulates bp(GO:"sensory processing") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dentate Gyrus
MeSH
Hippocampus

Evidence db73ebf56f
JSON

Nicotinic activation of inhibitory interneurons increases their activity and activates nitric oxide synthetase

act(a(HP:"inhibitory interneuron")) increases act(p(FPLX:NOS)) View Subject | View Object

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p(FPLX:CHRN) increases act(a(HP:"inhibitory interneuron")) View Subject | View Object

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p(FPLX:CHRN) increases act(p(FPLX:NOS)) View Subject | View Object

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Evidence 4471603666
JSON

Although alpha7 nAChRs have both presynaptic and postsynaptic expression (Frazier et al., 1998), their postsynaptic expression in humans is especially marked on inhibitory neurons of the hippocampus (Alkondon et al., 2000)

a(HP:"inhibitory interneuron") association a(MESH:"alpha7 Nicotinic Acetylcholine Receptor") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus

a(MESH:"alpha7 Nicotinic Acetylcholine Receptor") association a(HP:"inhibitory interneuron") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus

Evidence ea3c44cd01
JSON

Polymorphisms in the alpha7 5' promoter and in a nearby partial duplication of the gene, FAM7A, are associated with both schizophrenia and the defect in inhibition (Leonard et al., 2002)

act(a(HP:"inhibitory interneuron")) negativeCorrelation g(HGNC:CHRFAM7A, var("?")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

g(HGNC:CHRFAM7A, var("?")) association path(MESH:Schizophrenia) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

g(HGNC:CHRFAM7A, var("?")) negativeCorrelation act(a(HP:"inhibitory interneuron")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

path(MESH:Schizophrenia) association g(HGNC:CHRFAM7A, var("?")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

Evidence 897ee7ee2a
JSON

Thus, the brainstem can regulate hippocampal response in the presence of high sensory input.

a(MESH:"Brain Stem") regulates act(a(MESH:Hippocampus)) View Subject | View Object

Appears in Networks:

Evidence 275fbe3a07
JSON

The ‘‘volume transmission’’ hypothesis states that ACh released from presynaptic terminals spreads to more distant areas, reaching concentrations < 1 mM (Descarries et al., 1997), but that multiple presynaptic impulses produce enough summed release to activate receptors (Lester, 2004)

a(MESH:"Presynaptic Terminals") increases tloc(a(CHEBI:acetylcholine), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Appears in Networks:

Evidence 64a3018086
JSON

The neurodevelopmental program depends in part on alpha7 signaling (Liu et al.,2006)

act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) association bp(GO:"generation of neurons") View Subject | View Object

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bp(GO:"generation of neurons") association act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

Appears in Networks:

Evidence ca7db02db1
JSON

Three lines of evidence support the possibility that the failure of sensory inhibition in schizophrenia results from decreased expression of alpha7 nAChRs

a(MESH:"alpha7 Nicotinic Acetylcholine Receptor") increases bp(GO:"sensory processing") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

Evidence 4b111d1608
JSON

Yet some of the other genes identified, such as NRG1, are involved in the assembly of alpha7 nAChRs, further supporting a potential link between alpha7 nAChRs and schizophrenia (Mathew et al., 2007)

a(MESH:"alpha7 Nicotinic Acetylcholine Receptor") association path(MESH:Schizophrenia) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

g(HGNC:NRG1) increases a(MESH:"alpha7 Nicotinic Acetylcholine Receptor") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

path(MESH:Schizophrenia) association a(MESH:"alpha7 Nicotinic Acetylcholine Receptor") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

Evidence b35f1be234
JSON

Because excess activation of nAChRs damages neuronal health and brain function, organisms have a clear need to restrict the degree of nAChR activation

act(a(MESH:Brain)) negativeCorrelation act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

a(MESH:Neurons) negativeCorrelation act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

act(p(FPLX:CHRN)) negativeCorrelation act(a(MESH:Brain)) View Subject | View Object

Appears in Networks:

act(p(FPLX:CHRN)) negativeCorrelation a(MESH:Neurons) View Subject | View Object

Appears in Networks:

Evidence 419cad395e
JSON

Nicotinic receptor control over GABAergic neuronal development and mature activity may represent a point of convergence for diseases such as schizophrenia (see next section), some amblyopias (Bavelier et al., 2010), and some epilepsies (Klaassen et al., 2006), which distort the excitatory-inhibitory balance in general and implicate GABAergic signaling defects in particular

bp(GO:"GABAergic neuron differentiation") association path(MESH:Schizophrenia) View Subject | View Object

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bp(GO:"GABAergic neuron differentiation") association path(MESH:Amblyopia) View Subject | View Object

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p(FPLX:CHRN) regulates bp(GO:"GABAergic neuron differentiation") View Subject | View Object

Appears in Networks:

path(MESH:Amblyopia) association bp(GO:"GABAergic neuron differentiation") View Subject | View Object

Appears in Networks:

path(MESH:Schizophrenia) association bp(GO:"GABAergic neuron differentiation") View Subject | View Object

Appears in Networks:

Evidence eb117583c6
JSON

Neuronal maturation and loss of synaptic lability appear to be correlated with the onset of lynx1 expression

bp(GO:"neuron maturation") positiveCorrelation p(HGNC:LYNX1) View Subject | View Object

Appears in Networks:

bp(GO:"synapse maturation") negativeCorrelation p(HGNC:LYNX1) View Subject | View Object

Appears in Networks:

p(HGNC:LYNX1) positiveCorrelation bp(GO:"neuron maturation") View Subject | View Object

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p(HGNC:LYNX1) negativeCorrelation bp(GO:"synapse maturation") View Subject | View Object

Appears in Networks:

Evidence 439c64a08e
JSON

In 2011, we know that cholinergic actions in the brain govern various processes: cognition (attention and executive function) (Couey et al., 2007; Levin and Rezvani, 2007; Heath and Picciotto, 2009; Howe et al., 2010), learning and memory (Gould, 2006; Couey et al., 2007; Levin and Rezvani, 2007), mood (anxiety, depression) (Picciotto et al., 2008), reward (addiction, craving) (Tang and Dani, 2009), and sensory processing (Heath and Picciotto, 2009)

bp(GO:"sensory processing") association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

bp(GO:"synaptic transmission, cholinergic") association bp(GO:cognition) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

bp(GO:"synaptic transmission, cholinergic") association bp(GO:learning) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

bp(GO:"synaptic transmission, cholinergic") association bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

bp(GO:"synaptic transmission, cholinergic") association path(MESH:Anxiety) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

bp(GO:"synaptic transmission, cholinergic") association path(MESH:Depression) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

bp(GO:"synaptic transmission, cholinergic") association bp(GO:"sensory processing") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

bp(GO:cognition) association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

bp(GO:learning) association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

bp(GO:memory) association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:Anxiety) association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:Depression) association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence d4a1c3d1dd
JSON

While genetic linkages of lynx family members to neurological disorders have not been found, evidence for cholinergic dysregulation has been linked to a lynx family member expressed in nonneuronal tissues and involved in human disease (Chimienti et al., 2003), and as such, alterations in lynx dosage may be useful in ameliorating cognitive decline associated with neuropsychiatric disorders.

bp(GO:"synaptic transmission, cholinergic") association p(HGNC:LYNX1) View Subject | View Object

Appears in Networks:

p(HGNC:LYNX1) association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

p(HGNC:LYNX1) association path(MESH:"Cognitive Dysfunction") View Subject | View Object

Appears in Networks:

path(MESH:"Cognitive Dysfunction") association p(HGNC:LYNX1) View Subject | View Object

Appears in Networks:

Evidence b397fffeb1
JSON

Single-nucleotide polymorphisms found in the human alpha5, alpha3, beta4 gene cluster are associated with nicotine dependence and its age-dependent onset; number of cigarettes smoked per day and ‘‘pleasurable buzz’’ elicited by smoking; alcoholism, sensitivity to the depressant effects of alcohol, and age of alcohol initiation; cocaine dependence; opioid dependence; lung cancer; and cognitive flexibility (Erlich et al., 2010; Hansen et al., 2010; Improgo et al., 2010; Saccone et al., 2010; Zhang et al., 2010)

bp(GO:cognition) positiveCorrelation p(HGNC:CHRNA5, var("?")) View Subject | View Object

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bp(GO:cognition) positiveCorrelation p(HGNC:CHRNA3, var("?")) View Subject | View Object

Appears in Networks:

bp(GO:cognition) positiveCorrelation p(HGNC:CHRNB4, var("?")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA3, var("?")) positiveCorrelation path(MESH:"Tobacco Use Disorder") View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA3, var("?")) positiveCorrelation path(MESH:Alcoholism) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA3, var("?")) positiveCorrelation path(MESH:"Cocaine-Related Disorders") View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA3, var("?")) positiveCorrelation path(MESH:"Opioid-Related Disorders") View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA3, var("?")) positiveCorrelation path(MESH:"Lung Neoplasms") View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA3, var("?")) positiveCorrelation bp(GO:cognition) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA5, var("?")) positiveCorrelation path(MESH:"Tobacco Use Disorder") View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA5, var("?")) positiveCorrelation path(MESH:Alcoholism) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA5, var("?")) positiveCorrelation path(MESH:"Cocaine-Related Disorders") View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA5, var("?")) positiveCorrelation path(MESH:"Opioid-Related Disorders") View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA5, var("?")) positiveCorrelation path(MESH:"Lung Neoplasms") View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA5, var("?")) positiveCorrelation bp(GO:cognition) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNB4, var("?")) positiveCorrelation path(MESH:"Tobacco Use Disorder") View Subject | View Object

Appears in Networks:

p(HGNC:CHRNB4, var("?")) positiveCorrelation path(MESH:Alcoholism) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNB4, var("?")) positiveCorrelation path(MESH:"Cocaine-Related Disorders") View Subject | View Object

Appears in Networks:

p(HGNC:CHRNB4, var("?")) positiveCorrelation path(MESH:"Opioid-Related Disorders") View Subject | View Object

Appears in Networks:

p(HGNC:CHRNB4, var("?")) positiveCorrelation path(MESH:"Lung Neoplasms") View Subject | View Object

Appears in Networks:

p(HGNC:CHRNB4, var("?")) positiveCorrelation bp(GO:cognition) View Subject | View Object

Appears in Networks:

path(MESH:"Cocaine-Related Disorders") positiveCorrelation p(HGNC:CHRNA5, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:"Cocaine-Related Disorders") positiveCorrelation p(HGNC:CHRNA3, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:"Cocaine-Related Disorders") positiveCorrelation p(HGNC:CHRNB4, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:"Lung Neoplasms") positiveCorrelation p(HGNC:CHRNA5, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:"Lung Neoplasms") positiveCorrelation p(HGNC:CHRNA3, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:"Lung Neoplasms") positiveCorrelation p(HGNC:CHRNB4, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:"Opioid-Related Disorders") positiveCorrelation p(HGNC:CHRNA5, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:"Opioid-Related Disorders") positiveCorrelation p(HGNC:CHRNA3, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:"Opioid-Related Disorders") positiveCorrelation p(HGNC:CHRNB4, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:"Tobacco Use Disorder") positiveCorrelation p(HGNC:CHRNA5, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:"Tobacco Use Disorder") positiveCorrelation p(HGNC:CHRNA3, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:"Tobacco Use Disorder") positiveCorrelation p(HGNC:CHRNB4, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:Alcoholism) positiveCorrelation p(HGNC:CHRNA5, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:Alcoholism) positiveCorrelation p(HGNC:CHRNA3, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:Alcoholism) positiveCorrelation p(HGNC:CHRNB4, var("?")) View Subject | View Object

Appears in Networks:

Evidence 268b6a11f3
JSON

Each lynx paralog has a relative binding specificity and modulatory capability on alpha4beta2 (Miwa et al., 1999; Iban˜ ez-Tallon et al., 2002; Levitin et al., 2008), alpha3 (Arredondo et al., 2006), and alpha7 (Chimienti et al., 2003; Levitin et al., 2008; Hruska et al., 2009) nAChR subtypes; some interactions actually enhance nicotinic responses (Chimienti et al., 2003; Levitin et al., 2008), or their Ca2+ components (Darvas et al., 2009)

complex(a(HBP:"alpha-4 beta-2 nAChR"), p(HGNC:LYNX1)) regulates act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

Appears in Networks:

complex(a(HBP:"alpha-7-containing nAChR"), p(HGNC:LYNX1)) regulates act(a(HBP:"alpha-7-containing nAChR")) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRNA3), p(HGNC:LYNX1)) regulates act(p(HGNC:CHRNA3)) View Subject | View Object

Appears in Networks:

Evidence 89fdb756cb
JSON

Therefore, the evolutionary relationship between lynx modulators and the alpha-neurotoxins agrees with the view that lynx modulators govern critical control points in the pathway of nicotinic receptor signaling

p(HGNC:LYNX1) regulates act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

Evidence 07f9f6342d
JSON

Lynx1, the first discovered member of this family expressed in the brain (Miwa et al., 1999), has an overall inhibitory effect on nAChR function

p(HGNC:LYNX1) decreases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence 603ac13cd3
JSON

Removal of the molecular brake provided by lynx proteins can lead to nicotinic receptor hypersensitivity—larger direct nicotinic responses, slowed desensitization kinetics (Miwa et al., 2006), and enhanced sensitivity of the EPSC frequency in the cortex to nicotine (Tekinay et al., 2009)

p(HGNC:LYNX1) decreases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

Evidence ff483229dd
JSON

This indicates that lynx proteins exist, genetically, as upstream modulators of nicotinic receptor function and cholinergic signaling and can exert control over cholinergic-dependent processes

p(HGNC:LYNX1) regulates act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

Evidence ccbe214f11
JSON

Indeed, cholinergic enhancement (via cholinesterase inhibition) reopens the critical period for visual acuity in adult wild-type mice (Morishita et al., 2010), indicating that cellular mechanisms for robust plasticity are maintained in adulthood through the cholinergic system but are suppressed by the action of lynx.

p(HGNC:LYNX1) decreases bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

act(p(HGNC:ACHE)) decreases bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

Evidence ddc7e36150
JSON

Lynx1 upregulation during a critical neurodevelopmental period, the switch in the sign of GABAergic signaling, and coexpression of lynx with GABAergic subsets all indicate a possible role of lynx mediating the timing of such developmental transitions

p(HGNC:LYNX1) regulates bp(GO:"generation of neurons") View Subject | View Object

Appears in Networks:

Evidence 767b00a87c
JSON

Most brain HS nAChRs reside on presynaptic terminals, where they stimulate neurotransmitter release (Gotti et al., 2006; Albuquerque et al., 2009)

p(FPLX:CHRN) increases tloc(a(CHEBI:neurotransmitter), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Presynaptic Terminals

Evidence cf55001878
JSON

As GPI-anchored proteins can bind to transmembrane receptors intracellularly, the interactions of lynx with nAChRs could potentially alter receptor trafficking, stoichiometry, and surface number (Lester et al., 2009)

act(p(FPLX:CHRN)) association complex(p(FPLX:CHRN), p(HGNC:LYNX1)) View Subject | View Object

Appears in Networks:

surf(p(FPLX:CHRN)) association complex(p(FPLX:CHRN), p(HGNC:LYNX1)) View Subject | View Object

Appears in Networks:

complex(p(FPLX:CHRN), p(HGNC:LYNX1)) association act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

complex(p(FPLX:CHRN), p(HGNC:LYNX1)) association surf(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

Evidence d6442e232b
JSON

Abolishing receptor function through null mutations or pharmacological blockers of nAChRs abolished some of the gain-offunction phenotypes in lynx mouse models, indicating that nAChRs are necessary for the expression of lynx perturbations (Miwa et al., 2006)

p(FPLX:CHRN) regulates p(HGNC:LYNX1) View Subject | View Object

Appears in Networks:

Evidence bb4faf8ecd
JSON

Developmental changes in nAChR functions may play a role in nicotine addiction, as a central question in tobacco control is young adult smokers’ marked sensitivity to developing nicotine dependence (DSM-V Nicotine Workgroup, 2010; DiFranza et al., 2000; Difranza, 2010)

act(p(FPLX:CHRN)) association path(MESH:"Tobacco Use Disorder") View Subject | View Object

Appears in Networks:

path(MESH:"Tobacco Use Disorder") association act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

Evidence 5d23567cac
JSON

Recent studies provide evidence both that nicotinic signaling partially underlies these schizophrenia-related inhibitory defects and that nicotinic drugs have possible therapeutic roles

act(p(FPLX:CHRN)) association path(MESH:Schizophrenia) View Subject | View Object

Appears in Networks:

path(MESH:Schizophrenia) association act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

Evidence a6131f16bf
JSON

Finally, nAChRs exist in complexes in the brain; interacting proteins engage in complexes with nAChRs and aid in the assembly and trafficking of nAChR to the plasma membrane; examples are RIC-3 (Lansdell et al., 2005), 14-3-3 proteins (Jeanclos et al., 2001), neurexins (Cheng et al., 2009), and VILIP-1 (Lin et al., 2002)

complex(a(INTERPRO:"14-3-3 protein"), p(FPLX:CHRN)) increases p(FPLX:CHRN) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

complex(a(INTERPRO:"14-3-3 protein"), p(FPLX:CHRN)) increases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

complex(p(FPLX:CHRN), p(HGNC:RIC3)) increases p(FPLX:CHRN) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

complex(p(FPLX:CHRN), p(HGNC:RIC3)) increases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

complex(p(FPLX:CHRN), p(HGNC:VSNL1)) increases p(FPLX:CHRN) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

complex(p(FPLX:CHRN), p(HGNC:VSNL1)) increases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

complex(p(FPLX:CHRN), p(INTERPRO:Neurexin)) increases p(FPLX:CHRN) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

complex(p(FPLX:CHRN), p(INTERPRO:Neurexin)) increases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence e667aac0ef
JSON

Proteins that engage nAChRs within stable complexes, such as lynx family members, provide a homeostatic influence over nicotinic receptor systems

complex(p(FPLX:CHRN), p(HGNC:LYNX1)) regulates act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

Evidence 5fab7832b4
JSON

In an alpha4beta2* nAChR-expressing cell, coexpression of lynx1 results in reduced agonist sensitivity, accelerated onset of desensitization, and slower recovery from desensitization (Ibanez-Tallon et al., 2002)

composite(a(HBP:"alpha-4 beta-2 nAChR"), p(HGNC:LYNX1)) decreases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

Evidence 6ab61a2048
JSON

In most regions that receive cholinergic innervation, the high density of acetylcholinesterase (which can hydrolyze ACh at a rate of one per 100 ms!) might vitiate the volume transmission mechanism

p(HGNC:ACHE) increases deg(a(CHEBI:acetylcholine)) View Subject | View Object

Appears in Networks:

Evidence ea2179b5e4
JSON

Mutations in nicotinic receptor subunits are linked to human disease, alpha4 and beta2 in some epilepsies, alpha7 in schizophrenia, and alpha5 in nicotine addiction; and each mutation ultimately manifests itself as an imbalance in the properties of neuronal circuits

p(HGNC:CHRNA4, var("?")) positiveCorrelation path(MESH:Epilepsy) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA5, var("?")) positiveCorrelation path(MESH:"Tobacco Use Disorder") View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7, var("?")) positiveCorrelation path(MESH:Schizophrenia) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNB2, var("?")) positiveCorrelation path(MESH:Epilepsy) View Subject | View Object

Appears in Networks:

path(MESH:"Tobacco Use Disorder") positiveCorrelation p(HGNC:CHRNA5, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:Epilepsy) positiveCorrelation p(HGNC:CHRNA4, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:Epilepsy) positiveCorrelation p(HGNC:CHRNB2, var("?")) View Subject | View Object

Appears in Networks:

path(MESH:Schizophrenia) positiveCorrelation p(HGNC:CHRNA7, var("?")) View Subject | View Object

Appears in Networks:

Evidence 4257789f2b
JSON

Autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE) is caused by missense mutations in either the alpha4 or the beta2 subunit

p(HGNC:CHRNA4, var("?")) increases path(HBP:"Autosomal Dominant Nocturnal Frontal Lobe Epilepsy") View Subject | View Object

Appears in Networks:

p(HGNC:CHRNB2, var("?")) increases path(HBP:"Autosomal Dominant Nocturnal Frontal Lobe Epilepsy") View Subject | View Object

Appears in Networks:

Evidence dd6806fadc
JSON

For instance, early expression of lynx1 family member, PSCA, prevents programmed cell death of parasympathetic neurons (Hruska et al., 2009)

p(HGNC:PSCA) decreases bp(GO:"programmed cell death") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
parasympathetic neuron

Evidence 026b70691a
JSON

This transporter lowers the internal Cl- concentration of the neuron and changes GABA from a depolarizing to a hyperpolarizing or inhibitory neurotransmitter

p(HGNC:SLC12A5) decreases a(CHEBI:chloride) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:SLC12A5) regulates act(a(CHEBI:"gamma-aminobutyric acid")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

Evidence 6378cb1929
JSON

As a consequence of nAChR hypersensitivity, lynx1 knockout mice display increased levels of Ca2+ in neurons, enhancements in synaptic efficacy, and improved learning and memory functions (Miwa et al., 2006; Darvas et al., 2009; Tekinay et al., 2009)

p(MGI:Lynx1) decreases a(CHEBI:"calcium(2+)") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

p(MGI:Lynx1) decreases bp(MESH:"Synaptic Transmission") View Subject | View Object

Appears in Networks:

p(MGI:Lynx1) decreases bp(GO:learning) View Subject | View Object

Appears in Networks:

p(MGI:Lynx1) decreases bp(GO:memory) View Subject | View Object

Appears in Networks:

Evidence 707325546b
JSON

For instance, adult lynx1KO mice display heightened ocular dominance plasticity after the normal close of the critical period (Morishita et al., 2010)

p(MGI:Lynx1) decreases bp(MESH:"Dominance, Ocular") View Subject | View Object

Appears in Networks:

Evidence 27b3d2d60b
JSON

These findings indicate that suppression of the cholinergic system by lynx proteins stabilizes neural circuitry

p(MGI:Lynx1) decreases bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

p(MGI:Lynx1) increases a(MESH:Neurons) View Subject | View Object

Appears in Networks:

Evidence f50a0a8219
JSON

Third, persons with schizophrenia have the greatest rate and intensity of cigarette smoking of any identifiable subgroup in the population

path(MESH:"Tobacco Use Disorder") positiveCorrelation path(MESH:Schizophrenia) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

path(MESH:Schizophrenia) positiveCorrelation path(MESH:"Tobacco Use Disorder") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Schizophrenia

Evidence 78c31dc3fe
JSON

However, when all genetic factors are eliminated by studying monozygotic twins who are discordant for both tobacco use and Parkinson’s disease, tobacco smoking and chewing still decrease the risk of Parkinson’s disease (Tanner et al., 2002; Wirdefeldt et al., 2005)

path(MESH:"Tobacco Use") decreases path(MESH:"Parkinson Disease") View Subject | View Object

Appears in Networks:

path(MESH:Smoking) decreases path(MESH:"Parkinson Disease") View Subject | View Object

Appears in Networks:

Evidence a5079e0ab8
JSON

In many persons with schizophrenia, cerebral evoked potential recording shows diminished inhibition of the response to repeated stimuli (Adler et al., 1982) (Figure 2A), and animal models of this phenomenon point to a defect in hippocampal inhibition

path(MESH:Schizophrenia) increases act(a(MESH:Hippocampus)) View Subject | View Object

Appears in Networks:

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.