PubMed: 25881725

Title
Selective activation of α7 nicotinic acetylcholine receptor by PHA-543613 improves Aβ25-35-mediated cognitive deficits in mice.
Journal
Neuroscience
Volume
298
Issue
None
Pages
81-93
Date
2015-07-09
Authors
Babri S | Mahmoudi J | Sadigh-Eteghad S | Shanehbandi D | Talebi M

Evidence de33edab67

Moreover in Ab-received mice, treatment with PHA and Gal improved the acquisition performance on comparing with the normal saline group (p<0.001)

Evidence a8081480be

The analysis also showed significant enhancing effects of PHA and Gal on the time spent in the target quadrant on comparing with the normal saline in AD mice (p<0.001). Also, in comparison with the control group, PHA-treated AD animals did not have a significant difference (p>0.05) on the time spent in the target quadrant, but in the Gal group it was significantly lower (p<0.001) (Fig. 3).

Evidence e2f3eba31b

Also, no alterations in the expression of a7 nAChR mRNA were observed in pretreatment with normal saline or MLA in PHA- or Gal-treated groups (p>0.05). In the same way, the pattern of mRNA expression in the cortex (data not shown) was similar to the hippocampus (Fig. 7).

Evidence 0b354b9a9d

The analysis also showed significant effects of PHA and Gal on the protein levels on comparing with normal saline in AD mice (p<0.001). Moreover, Gal could not completely protect the a7 nAChR protein level in AD animals. This group has a lesser a7 nAChR protein level in comparison with the control group (p<0.001) (Fig. 8). The groups showed results in the cortex similar to those observed in the hippocampus (data not shown)

Evidence 0797448e59

Inter-group analysis showed that the protein level decreased by pretreatment with selective a7 nAChR antagonist MLA (p<0.001). PHA and Gal prevent receptor destroying in AD animals, but this effect is completely abolished by MLA (p<0.001) (Fig. 9). The groups showed results in the cortex similar to those observed in the hippocampus (data not shown).

Evidence b6e6a325ea

Notably, PHA could completely block the Ab-impaired task acquisition and reduce escape-latency to the normal level. Furthermore, the effect of PHA against the Ab-impaired task acquisition could be abolished by the pre-treatment of the a7 nAChR antagonist MLA (p<0.001). It was also noted that blockade of a7 nAChR by MLA in the Gal-treated group resulted in a significant prolongation of the escape-latency on comparing with the Gal group (p<0.001) (Fig. 2).

Evidence 7cda86b293

MLA could completely block the PHA-induced spatial memory improvement (p<0.001). Furthermore, the effect of Gal against the Ab-impaired reference memory could be abolished by the pre-treatment of the a7 nAChR antagonist MLA (p<0.001). However, a7 nAChR blockage in the Gal group has a lesser effect on reference memory in comparison of blockage of that receptor in the PHA group (p<0.05) (Fig. 4).

Evidence 292916f9ed

Effect of a7 nAChRs blockage on time spent in target quadrant in probe trials. The implications of the a7 nAChRs on PHA- or Gal-induced spatial memory enhancement were investigated by pretreatment with normal saline or MLA. A two-way ANOVA revealed significant differences of treatment [F(1,56)=4.24, p<0.05], pretreatment [F(1,56)=96.87, p<0.001] and treatment  pretreatment interaction [F(1,32)=10.69, p<0.01]. Inter-group analysis showed that this effect was blocked by the selective a7 nAChR antagonist MLA (p<0.001).

Evidence b4b1bd5894

Inter-group analysis showed that Ab increased escape latency in MWM in comparison with normal saline and sham groups (p<0.001). In addition, sham operation did not have a significant effect on escape latency in comparison with the normal saline group (p>0.05).

Evidence a8685ef489

Time spent in target quadrant in probe trials. On the probe trial, there was a statistically significant difference between groups as determined by a one-way ANOVA (F(4,70)=35.21, p<0.001). Post hoc analysis revealed a significant effect of Ab injection on the time spent in the target quadrant, indicating that the Ab decreased the searching time in the target quadrant on comparing with the control (p<0.001).

Evidence 6300675fa2

In contrast, brain sections of animals treated with 10-nmol-aged Ab25–35 peptide demonstrated the presence of numerous and distinct extracellular amyloid deposits, widely disseminated throughout the brain (Fig. 5).

Evidence aa25c1ad04

mRNA levels of a7 nAChR subunit. Relative quantification by using a real-time RT-PCR did not reveal any significant differences in the levels of mRNA for the a7 nAChR subunits either in the hippocampus or in the cortex of various groups (p>0.05). The groups showed results in the cortex (data not shown) similar to those observed in the hippocampus (Fig. 6).

Evidence 9813ae4e96

Post hoc analysis revealed that, levels of the a7 nAChR protein in normal saline-treated AD mice were significantly lower than its level in the control animals (p<0.001).

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