Alzheimer's disease (AD) is associated with the accumulation of beta-amyloid and leads to cognitive impairment. Numerous studies have established that neuronal calcium homeostasis is perturbed in AD. Recently, transient receptor potential vanilloid 2 (TRPV2) channels, a non-selective calcium-permeable channel, have been investigated in several diseases. However, the role of the TRPV2 channel has not been investigated in AD yet. In this study, intracerebroventricular administration of beta-amyloid (10 microg) to Sprague Dawley rats resulted in cognitive impairment which was evident from the assessment of cognitive tests. Also, TRPV2 mRNA and protein expression were found to be upregulated, while the expression of Ca(2+/)calmodulin-dependent protein kinase II (p-CaMKII-Thr-286), glycogen synthase kinase 3beta (p-GSK-3beta-Ser-9), cAMP response element-binding protein (p-CREB-Ser-133), and postsynaptic density protein 95 (PSD-95) were downregulated in the hippocampus of beta-amyloid-treated animals. Even, beta-amyloid-treated animals showed upregulation of mRNA level of calcium buffering proteins (parvalbumin and calsequestrin) and calcineurin A (PPP3CA) in the hippocampus. Acetylcholinesterase activity was also increased in the cortex of beta-amyloid-treated animals. Three-week treatment with tranilast showed improvement in the cognitive parameters which was associated with a decrease in TRPV2 expression and AChE activity. Additionally, an increase in the protein expression of p-CaMKII, p-GSK-3beta, p-CREB and PSD-95 in the hippocampus was found. Downregulation in the mRNA level of calcium buffering proteins (parvalbumin and calsequestrin) and calcineurin A in the hippocampus was also seen. These results reveal the importance of TRPV2 channels in the beta-amyloid-induced cognitive deficits and suggest TRPV2 as a potential target for AD.
        
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Thapak P, Bishnoi M, Sharma SS (2021) Tranilast, a Transient Receptor Potential Vanilloid 2 Channel (TRPV2) Inhibitor Attenuates Amyloid beta-Induced Cognitive Impairment: Possible Mechanisms Neuromolecular Med
Thapak P, Bishnoi M, Sharma SS (2021) Neuromolecular Med