Calcitonin gene-related peptide enhances CREB phosphorylation and attenuates tau protein phosphorylation in rat brain during focal cerebral ischemia/reperfusion.

ABSTRACT

Calcitonin gene-related peptide (CGRP) is a potent vasodilator and immune cell modulator. Exogenous CGRP could increase the cerebral blood flow significantly and protect the ischemic neurons, but its mechanism is not entirely clear. The effect of CGRP on the expressions of CREB and tau in the ipsilateral parietal cortex were detected in focal cerebral ischemia/reperfusion model. The expression of CREB mRNA decreased in ischemia/reperfusion group (I/R group) compared with that of the sham operation group, and it got highest in CGRP group. CREB expression was lesser in I/R group than sham group, but it became more in CGRP group than I/R group. Phospho-CREB became more in I/R group, and it got most in CGRP group in the cortex. No significant difference was observed on Tau mRNA expression in all the groups. The level of tau hyperphosphorylation at Ser199/202 site and total tau in rat parietal cortex were significantly higher in I/R group than sham group. CGRP significantly inhibited tau hyperphosphorylation and the level of total tau also significantly reduced in CGRP group than that in I/R group. CGRP can upregulate the expression of CREB and phospho-CREB and attenuate the level of tau hyperphosphorylation in the ischemic neurons of the parietal cortex during focal cerebral ischemia/reperfusion. Phosphorylating CREB and inhibiting tau phosphorylation are probably involved in the mechanism of protective effect of CGRP to ischemic neurons.