Region-specific changes in the immunoreactivity of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide receptors (VPAC₂, and PAC₁ receptor) in the aged rat brains

Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) have been implicated in a large array of physiological and patho-physiological processes through their receptors (VPAC₁, VPAC₂, and PAC₁ receptor) in the central nervous system. Previously, we demonstrated age-related decreases in VPAC₁ receptor expression in the rat brain providing a possible basis of several age-induced functional changes in the aged brain. In the current study, we also examined age-related changes in PAC₁ and VPAC₂ receptors in aged rat brains using an immunohistochemical approach. We found that PAC1 immunoreactivity was significantly increased in the hippocampal formation, hypothalamus, thalamus, midbrain septal nuclei, and white matter of aged rats compared with young control rats although its distribution pattern was not altered. In contrast, both distribution pattern and immunoreactivity of VPAC₂ receptor remained unchanged in aged rat brains. These results suggest that the PACAP/VIP receptors exhibit specific expressional changes in the aged brain and that these specific changes could underlie age-associated memory and cognitive functional declines as well as several other age-induced functional changes in the brain. However, the exact regulatory mechanism and its functional significance require further elucidation.