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

Abstract

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 Aβ1-40 biochemical assessments were performed using enzyme-linked immunosorbent assay (ELISA) kits. Furthermore, evaluations of brain amyloid precursor protein 695 (APP695) mRNA expression by RT-PCR and AGE expression by immunohistochemistry were carried out. Ovariectomized rats exhibited memory impairment and Aβ production disorder with upregulated APP695 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.

Effects of Aminoguanidine on Apoptosis in the Hippocampus and Memory Disorder in a Rat Model of Alzheimer’s Disease

“…Amg is a free radical scavenger that could inhibit AGEs and protect against oxidative injury in the brain (11,17,19). Zhang et al demonstrated that the neuroprotective effects of Amg can be attributed to the capability to reduce Aβ level and anti-AGEs activity (22). It has been shown that the interaction of AGEs with receptor for AGEs (RAGE) induces oxidative stress and inflammation in neurons (26).…”

“…Amg is a potent inhibitor of RAGE in the brain. Therefore, it prevents Aβ aggregation and memory impairment (22). Alikhani et al disclosed that the intraperitoneal injection of Amg decreased oxidative stress indicators such as catalase, superoxide dismutase, and thiol in the brain and improved learning and memory impairments (36).…”

“…Beheshti et al exhibited that Amg has protective effects against LPS-induced memory loss and decreased Aβ and oxidative stress (11,16). A recent study showed that Amg has protective effects against ovariectomy-induced memory defect and Aβ production disorder (22). Other studies have shown that one month of Amg injection improves memory by modulating Bcl-2 expression in diabetic rats (23,24).…”

Pathophysiological Association of Alzheimer’s Disease and Hypertension: A Clinical Concern for Elderly Population

“… 130 , 131 Thus, HTN is enough to trigger cerebromicrovascular impairment. 132 , 133 In another novel study, the amyloid genic gene is overexpressed in the brain of aging and HTN-induced mouse. 134 Furthermore, activating the receptor for advanced glycation end-products (RAGE) in cerebral microvessels is also thought to be a route to the processes of HTN-induced AD development.…”