Tranilast, a Transient Receptor Potential Vanilloid 2 Channel (TRPV2) Inhibitor Attenuates Amyloid β-Induced Cognitive Impairment: Possible Mechanisms

In this study, intracerebroventricular administration of β-amyloid (10 μg) to Sprague Dawley rats resulted in cognitive impairment which was evident from the assessment of co gnitive tests. Also, TRPV2 mRNA and protein expression were found to be upregulated, while the expression of Ca2+/calmodulin-dependent protein kinase II (p-CaMKII-Thr-286), glycogen synthase kinase 3 β (p-GSK-3β-Ser-9), cAMP response element-binding protein (p-CREB-Ser-133), and postsynaptic density protein 95 (PSD-95) were downregulated in the hippocampus of β-amyloid-treated animals. Even, β-amyloid-treated animals showed upregulation of mRNA level of calcium buffering proteins (parvalbumi n and calsequestrin) and calcineurin A (PPP3CA) in the hippocampus. Acetylcholinesterase activity was also increased in the cortex of β-amyloid-treated animals. Three-week treatment with tranilast showed improvement in the cognitive parameters which was associated with a decrease in TRPV2 expressio n and AChE activity. Additionally, an increase in the protein expression of p-CaMKII, p-GSK-3β, 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 re sults reveal the importance of TRPV2 channels in the β-amyloid-induced cognitive deficits and suggest TRPV2 as a potential target for AD.

Source: NeuroMolecular Medicine - July 6, 2021 Category: Neurology Source Type: research