Thapak_2020_Neurochem.Int__104783

Transient receptor potential (TRP) channels are Ca(2+) permeable non-selective cation channels which play a pivotal role in diabetes and diabetic complications. Among diabetic complications, diabetes-induced cognitive impairment is a major CNS complication. The role of several TRP channels has been investigated extensively for their diverse Ca(2+) regulating mechanism, and recently their role has been postulated in the progression of neurodegenerative disorders. However, the role of TRPV2 has not been investigated yet. Therefore, in the present study, the involvement of TRPV2 channels was investigated in diabetes-induced cognitive impairment using TRPV2 inhibitor, tranilast. High glucose exposure in rat C6 glial cells enhances the Ca(2+)-entry through TRPV2 channels. In our in-vivo study, diabetic rats showed increased gene and protein expression of TRPV2 in the hippocampus. Subsequent increase in the acetylcholinesterase activity in the cortex, as well as decrease in the phosphorylation of Ca(2+)/calmodulin-dependent protein kinase II (p-CaMKII-Thr-286), p-GSK-3beta (Ser-9), p-CREB (Ser-133) and postsynaptic density protein 95 (PSD-95) in hippocampus, was also observed this led to the impairment in the learning and memory as evident from behavioral parameters such as Morris water maze test, passive avoidance and Y-maze test paradigm. Three week treatment with tranilast (30 and 100mg/kg, p.o.) showed improvement in learning and memory associated behaviours (Morris water maze test, passive avoidance, and Y-maze test) by increasing the p-CaMKII (Thr-286), p-GSK-3beta (Ser-9), p-CREB (Ser-133) and PSD-95 in hippocampus. Cortical acetylcholinesterase activity was also reduced by the tranilast. These findings depicted that TRPV2 inhibition may be an effective treatment strategy in diabetes-induced cognitive deficits.