The Effect of Rivastigmine on Enhanced Glucose Metabolism and Enhanced Synaptic Plasticity in the Hippocampus of Aged Rats: A Sex-Dependent Study

The aim of this study was to investigate the enhancing effects of rivastigmine administration on hippocampal glucose metabolism, insulin signaling pathways, and synaptic plasticity, independently of cognitive function, in an aged rat model. Thirteen-month-old male and female Wistar rats were randomly divided into four groups: male control, male rivastigmine, female control, and female rivastigmine. Rivastigmine (2 mg/kg) or an equivalent volume of physiological saline was administered intraperitoneally for 21 days. At the end of the experiment, the animals were sacrificed, and hippocampal tissues were collected. Protein levels in hippocampal tissue were evaluated using Western blot, and the expression of total GSK3β, p-GSK3β (Ser9), total Akt, p-Akt, GLUT4, SIRT1, and PSD95 was examined. The results showed that total GSK3β and total Akt levels were significantly higher in the male rivastigmine group compared to the female rivastigmine group (p < 0.01), while PSD95 levels were higher in the male control group compared to the female rivastigmine group (p < 0.05). No significant differences were found between the groups in other parameters. The findings suggest that rivastigmine administration has limited effects on hippocampal insulin signaling pathways, glucose metabolism, and protein expression related to synaptic function, and that these effects may vary depending on gender.