Differential activation of Gsk-3β in the cortex and the hippocampus induces cognitive and behavioural impairments in middle-aged ovariectomized rat

Glycogen synthase kinase-3 (Gsk-3β) aberration act as a crucial pathogenic factor in several neurological conditions. However its role in menopause associated behavioural impairments is still not unclear. The present study was designed to understand the role of Gsk-3β in the progression of neurobehavioural impairments in middle-aged ovariectomized (ovx) rats. The animals showed a significant impairment in spatial and recognition memory, along with anxiety and depression-like behaviour following 22 weeks of ovx. The genomic expression of ERα, ERβ, Nrf2, HO-1, TNFα, and IL-6 was altered in both the cortex and the hippocampus of ovx rats. Protein expression of p-Gsk-3β(Ser(9)) was significantly downregulated in the cortex after ovx. However, the hippocampus showed a surprisingly opposite trend in the levels of p-Gsk-3β(Ser(9)) as that of the cortex. Differential activation of Gsk-3β and its downstream proteins such as β-catenin and p-mTOR were also altered following ovx. The study concluded that differential activation of Gsk-3β, along with oxidative stress and neuroinflammation in the cortex and the hippocampus, leads to the induction of cognitive and behaviour impairments in ovx rats.