INTRACORTICAL GLUTAMATE PERFUSION IN-VIVO INDUCES CELLULAR ALTERATIONS IN SPECIFIC PROTEIN-KINASE-C ISOFORMS AND AMYLOID PRECURSOR PROTEIN

This study investigated the immunostaining of protein kinase C (PKC) i soforms and amyloid precursor protein (APP) in rat brain cortex and de termined alterations following an excitotoxic challenge in vivo. Cellu lar alterations in APP and PKC isoforms (alpha, beta, gamma, delta, ep silon, and zeta) following glutamate perfusion in the rat parietal cor tex were compared with NaCl perfusion. In all animals, two histologica l zones could be defined consistently, a necrotic core and a boundary zone immediately adjacent to the core. Following glutamate and NaCl pe rfusion, cellular immunoreactivity to PKC isoforms and amino-terminal APP was significantly reduced within the necrotic core. Striking carbo xyterminal APP immunoreactivity was observed in some neurons remaining within the necrotic core. In the boundary of the glutamate lesion, th e perikarya of most neurons were intensely immunoreactive to PKC alpha and beta. Furthermore, within the boundary zone, enhanced immunoreact ivity within neuronal perikarya was observed to amino-terminal APP and , to a lesser extent, carboxy-terminal APP. Increased immunostaining o f PKC alpha and beta and APP at the boundary zone was a consistent fea ture of intracortical glutamate perfusion and was not observed followi ng NaCl perfusion. There were minimal alterations in PKC isoforms gamm a, delta, epsilon, and zeta, in the boundary region following intracor tical glutamate or NaCl perfusion. There was no astrocytic response, a s detected by GFAP immuno-reactivity, at the boundary zone. These find ings indicate that there is a topographical relationship between cellu lar alterations of specific PKC isoforms and APP following an excitoto xic challenge in vivo. (C) 1997 Academic Press.