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PubMed: 30008470

Title
Activity-dependent neuroprotective protein (ADNP) is an alcohol-responsive gene and negative regulator of alcohol consumption in female mice.
Journal
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Volume
44
Issue
None
Pages
415-424
Date
2019-01-01
Authors
Barak S | Ziv Y | Shaham O | Lezmy N | Rahamim N | Elkon R | Even-Chen O | Giladi E | Gozes I | Malishkevich A

Evidence 049f865680
JSON

No changes in Adnp levels were detected in the VTA or NAc (p’s > 0.05).

path(MESH:"Alcohol Drinking") causesNoChange p(HGNC:ADNP) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Ventral Tegmental Area
Gender
Male
Gender
Female

Evidence 2fe7258b50
JSON

NAP has been shown to ameliorate Adnp deficiencies in the haploinsufficient mouse model [25], mechanistically by enhancing ADNP association with its microtubule and autophagy targets

a(PUBCHEM:9832404) increases complex(a(GO:microtubule), p(HGNC:ADNP)) View Subject | View Object

Appears in Networks:

Evidence b49170aec1
JSON

These results indicate that restoration of ADNP function by NAP administration rescues the wild type phenotype of the Adnp+/− mice, by reversing the abnormal increase in alcohol intake seen in Adnp haploinsufficient female mice

a(PUBCHEM:9832404) increases act(p(HGNC:ADNP)) View Subject | View Object

Appears in Networks:
Annotations
Gender
Female

Evidence c19e05134b
JSON

Strikingly, NAP treatment reduced alcohol consumption in Adnp+/− mice, which did not differ from Adnp+/+ controls.

composite(a(PUBCHEM:9832404), p(HGNC:ADNP, pmod(MESH:Haploinsufficiency))) decreases path(MESH:"Alcohol Drinking") View Subject | View Object

Appears in Networks:
Annotations
Gender
Female

Evidence b976a3dbb6
JSON

Originally, a reduction of 42% in the cortex, of 38% in cerebellum, and of 50% in hippocampus was observed in the levels of Adnp mRNA in Adnp+/− mice compared with Adnp intact mice

p(HGNC:ADNP, pmod(MESH:Haploinsufficiency)) decreases r(HGNC:ADNP) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebellum
MeSH
Cerebral Cortex
MeSH
Hippocampus

Evidence f7dc1d12a3
JSON

Importantly, Adnp+/− females showed higher alcohol consumption and preference, compared to female Adnp+/+ controls, whereas no difference was observed in males.

p(HGNC:ADNP, pmod(MESH:Haploinsufficiency)) increases path(MESH:"Alcohol Drinking") View Subject | View Object

Appears in Networks:
Annotations
Gender
Female

p(HGNC:ADNP, pmod(MESH:Haploinsufficiency)) causesNoChange path(MESH:"Alcohol Drinking") View Subject | View Object

Appears in Networks:
Annotations
Gender
Male

Evidence 81963ab005
JSON

As shown in Fig. 3e, f, we found no difference between genotypes in saccharin or quinine intake, suggesting that the effect of Adnp deficiency is specific to alcohol, and does not apply to sweet reinforcers or bitter-taste solutions

p(HGNC:ADNP, pmod(MESH:Haploinsufficiency)) increases path(MESH:"Alcohol Drinking") View Subject | View Object

Appears in Networks:
Annotations
Gender
Female

p(HGNC:ADNP, pmod(MESH:Haploinsufficiency)) causesNoChange tloc(a(CHEBI:saccharin), fromLoc(GO:"extracellular space"), toLoc(GO:intracellular)) View Subject | View Object

Appears in Networks:
Annotations
Gender
Female

p(HGNC:ADNP, pmod(MESH:Haploinsufficiency)) causesNoChange tloc(a(CHEBI:quinine), fromLoc(GO:"extracellular space"), toLoc(GO:intracellular)) View Subject | View Object

Appears in Networks:
Annotations
Gender
Female

Evidence d37418627b
JSON

As Fig. 4b depicts, over the first 2 weeks of drinking (no treatment or intranasal vehicle treatment) Adnp+/− females showed higher alcohol consumption as compared to their Adnp+/+ littermates, replicating our results above.

p(HGNC:ADNP, pmod(MESH:Haploinsufficiency)) increases path(MESH:"Alcohol Drinking") View Subject | View Object

Appears in Networks:
Annotations
Gender
Female

Evidence 642131aa00
JSON

For example, one of these common genes was transcription factor AP2 beta (TFAP2b), which is downregulated by chronic alcohol exposure [41]. This gene had a 3.8-fold increased expression in female Adnp+/− mice, and in contrast, a five-fold decreased expression in male Adnp+/− mice, as compared to sex-matched Adnp+/+controls.

p(HGNC:ADNP, pmod(MESH:Haploinsufficiency)) increases p(HGNC:TFAP2B) View Subject | View Object

Appears in Networks:
Annotations
Gender
Female

p(HGNC:ADNP, pmod(MESH:Haploinsufficiency)) decreases p(HGNC:TFAP2B) View Subject | View Object

Appears in Networks:
Annotations
Gender
Male

path(MESH:"Alcohol Drinking") decreases p(HGNC:TFAP2B) View Subject | View Object

Appears in Networks:

Evidence 37288f4b54
JSON

Together, our results indicate that reduced Adnp gene dosage leads to increased alcohol intake in female mice.

g(HGNC:ADNP) negativeCorrelation path(MESH:"Alcohol Drinking") View Subject | View Object

Appears in Networks:
Annotations
Gender
Female

path(MESH:"Alcohol Drinking") negativeCorrelation g(HGNC:ADNP) View Subject | View Object

Appears in Networks:
Annotations
Gender
Female

Evidence 2a764a4440
JSON

As shown in Fig. 1, we found that this sub-chronic alcohol treatment increased Adnp mRNA levels in the dorsal hippocampus 24 h, but not 2 h after the last alcohol injection, in both male and female mice (one-way ANOVA; males: F(2,10) = 5.94, p < 0.05; post-hoc, p < 0.02. Females: F(2,10) = 5.22, p < 0.05, post hoc, p < 0.05)

path(MESH:"Alcohol Drinking") increases r(HGNC:ADNP) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
Gender
Male
Gender
Female

Evidence 539f830afd
JSON

In addition, Adnp expression was increased at the 24 h time point in the NAc of female, but not male mouse (one-way ANOVA; females: F(2,9) = 10.87, p < 0.005; post hoc: p < 0.005; males: p > 0.05).

path(MESH:"Alcohol Drinking") increases p(HGNC:ADNP) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nucleus Accumbens
Gender
Female

path(MESH:"Alcohol Drinking") causesNoChange p(HGNC:ADNP) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nucleus Accumbens
Gender
Male

Evidence d7094a1757
JSON

We found no changes in the expression of Adnp in the VTA (p’s > 0.05).

path(MESH:"Alcohol Drinking") causesNoChange p(HGNC:ADNP) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Ventral Tegmental Area
Gender
Male
Gender
Female

Evidence b49f3e9429
JSON

We found that among male mice, Adnp mRNA levels were increased in the dorsal hippocampus after a 24 h alcohol drinking session, but the level returned to baseline (water-drinking controls) after 24 h of withdrawal (Fig. 2b; one-way ANOVA: F(2,13) = 5.32, p < 0.05, post hoc comparisons, p’s < 0.05)

path(MESH:"Alcohol Drinking") increases p(HGNC:ADNP) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
Gender
Male

Evidence cb37783e63
JSON

However, in female mice, the expression of Adnp was reduced after a 24-h alcohol-drinking session, and this reduction persisted after a 24-h withdrawal (Fig. 2c; one-way ANOVA: F(2,13) = 7.53, p < 0.01, post hoc comparisons, p’s < 0.05).

path(MESH:"Alcohol Drinking") decreases p(HGNC:ADNP) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
Gender
Female

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