Phycocyanin alleviates ICV-STZ induced cognitive and molecular deficits via PI3-Kinase dependent pathway

In this study, the effect of Phycocyanin (Pc) to ameliorate the cognitive dysfunction in experimental model of Alzheimer's disease (AD) was evaluated. Intracerebroventricular (ICV) induction of Streptozotocin (STZ) (3 mg/kg) was done bilaterally twice in rats on alternative days. Rats were injected with Pc (50, 100 mg/kg; i. p.) for 28 days daily for behavioural and cholinergic activity assessment. As the effect was only significant at 100 mg/kg, later molecular experiments were performed using the same only. STZ induction led to increased activity of hippocampal cholinesterases and BAX and decreased activity of BCL-2 and ChAT. It enhanced TNF-alpha, and NF-kappa B in rat's brain and reduced BDNF and IGF-1 levels. Dysfunctional insulin signaling and decreased gene expressions of PI3-K, AKT was also observed. However, Pc treatment significantly prevented STZ-induced increased activity of hippocampal cholinesterases and BAX as well as increased the levels of BCL-2 and ChAT. Neuroinflammation was significantly attenuated and BDNF and IGF-1 levels were upregulated. Further, Pc also alleviated dysfunctional insulin signaling as evidenced by increased gene expression of IRS-1, PI3-K, AKT. In conclusion, our study demonstrated the immense potential of Pc in attenuating STZ-induced cognitive decline and it may be further explored as a therapeutic agent in managing AD.