Acteoside improves hippocampal neurons damage and cognitive function in OVX rats

AimTo study the protective effect of acteoside (AE) on hippocampal neurons and its improvement on cognitive function in ovariectomy (OVX) rats, and to explore its influence on the ERα/BDNF/TrkB/PSD-95/SYP signaling pathway.MethodsA total of 140 female Sprague-Dawley (SD) rats were randomly divided into seven groups: sham group, model group, low-dose AE (L-AE) group, medium-dose AE (M-AE) group, high-dose AE (H-AE) group, estradiol group, and donepezil group. The estrogen-deficient rat model was established by OVX. After seven weeks of drug administration, the step-through test and novel object recognition test were used to evaluate the cognitive function of rats. HE staining and Golgi staining were employed to observe hippocampal neuron damage and changes in dendritic spines. ELISA was used to detect the contents of estradiol (E2) and anti-Müllerian hormone (AMH) in serum, as well as amyloid-beta 1-42 (Aβ1-42)in hippocampal tissue. Western blot was used to determine the expression levels of related proteins in hippocampal tissue.ResultsCompared with the sham group, the model group showed a significant increase in the number of errors in the step-through test, a significant decrease in step-through latency and novel object preference index, obvious damage to hippocampal neurons, reduced number and density of dendritic spines, a significant increase in Aβ1-42, a significant decrease in E2 and AMH, and significantly lower expression levels of ERα, BDNF, TrkB, PSD-95, and SYP proteins. Compared with the model group, the AE-treated groups exhibited a significant increase in step-through latency and novel object preference index, varying degrees of recovery from hippocampal neuron damage, an increase in the number and density of dendritic spines, a significant increase in E2, a significant decrease in Aβ1-42, and significantly higher expression levels of ERα, BDNF, TrkB, PSD-95, and SYP proteins.ConclusionsAE increases serum E2 content in OVX rats, regulates the ERα/BDNF/TrkB/PSD-95/SYP signaling pathway, enhances synaptic plasticity, and improves estrogen deficiency-induced nerve damage and cognitive impairment.