Aminoguanidine ameliorates ovariectomy-induced neuronal deficits in rats by inhibiting AGE-mediated Aβ production

Advanced glycation end products (AGEs) have been reported to cause neurodegeneration, senile plaque formation and spatial learning and memory deficits. There is much evidence describing the beneficial effects of aminoguanidine (AG) on the central nervous system; AG is able to inhibit the receptor for AGEs and beta-amyloid (Aβ) deposition in the brain, thus preventing cognitive decline and neurodegeneration. In this study, we investigated whether AG protects against ovariectomy-induced neuronal deficits and Aβ deposition in rats. Animals in the ovariectomy group (OVX) group, and those in the OVX+AG group were treated with AG (100 mg/kg/day) for 8 weeks. Learning and memory were evaluated using the electric Y maze. AGE and Aβ 1-40 biochemical assessments were performed using enzyme-linked immunosorbent assay (ELISA) kits. Furthermore, evaluations of brain amyloid precursor protein 695 (APP 695 ) mRNA expression by RT-PCR and AGE expression by immunohistochemistry were carried out. Ovariectomized rats exhibited memory impairment and Aβ production disorder with upregulated APP 695 mRNA and AGE expression levels. AG pretreatment relieved the ovariectomy-induced learning and memory disorder and significantly ameliorated the Aβ production disturbance and AGE generation. Additionally, pathological changes in morphology were also significantly recovered. Our data reveal that AG plays a potentially neuroprotective role against ovariectomy-induced learning and cognitive impairment and Aβ production disorder.