| First Author | Sadigh-Eteghad S | Year | 2015 |
| Journal | Neuroscience | Volume | 298 |
| Pages | 81-93 | PubMed ID | 25881725 |
| Mgi Jnum | J:224500 | Mgi Id | MGI:5662358 |
| Doi | 10.1016/j.neuroscience.2015.04.017 | Citation | Sadigh-Eteghad S, et al. (2015) Selective activation of alpha7 nicotinic acetylcholine receptor by PHA-543613 improves Abeta25-35-mediated cognitive deficits in mice. Neuroscience 298:81-93 |
| abstractText | Agonists of alpha7 nicotinic acetylcholine receptors (nAChRs) are currently being considered as therapeutic approaches for managing cognitive deficits in Alzheimer's disease (AD). Present study was designed to evaluate the effect of alpha7 nAChR selective activation by PHA-543613 (PHA) on beta-amyloid (Abeta)25-35-mediated cognitive deficits in mice. For this purpose, PHA (1mg/kg, i.p.), a selective alpha7 nAChR agonist, and galantamine (Gal) (3mg/kg, s.c.), an acetylcholine-esterase inhibitor (AChEI) effects on alpha7 nAChR were tested in Abeta25-35-received (intracerebroventricular, 10 nmol) mice model of AD. Methyllycaconitine (MLA) (1mg/kg, i.p.), a alpha7 nAChR antagonist, was used for receptor blockage effects evaluation. Working and reference memory in animals was assessed by the Morris water maze (MWM) task. The mRNA and protein levels of alpha7 subunit were analyzed by real-time PCR and Western blotting, respectively. PHA and Gal, ameliorate Abeta-impaired working and reference memory. However, Gal had less effect than PHA in this regard. Pretreatment with MLA reverses both Gal and PHA effects in MWM. PHA and Gal treatment prevent Abeta-induced alpha7 subunit protein reduction, but Gal has lesser effect than PHA. This effect blocked by pretreatment with MLA. In neither the pretreatment nor treatment group, the mRNA levels of nAChR alpha7 subunit were significantly changed. Therefore, alpha7 nAChR activation, reduces Abeta-induced cognitive deficits and increases the alpha7 protein level and subsequent neuron survival. However, blockage of receptor, increases Abeta toxicity and cognitive impairment and reduces the alpha7 nAChR protein level and flowing neuroprotection. |
