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) isoforms and amyloid precursor protein (APP) in rat brain cortex and determined alterations following an excitotoxic challenge in vivo. Cellular alterations in APP and PKC isoforms (alpha, beta, gamma, delta, epsilon, and zeta) following glutamate perfusion in the rat parietal cortex were compared with NaCl perfusion. In all animals, two histological zones could be defined consistently, a necrotic core and a boundary zone immediately adjacent to the core. Following glutamate and NaCl perfusion, cellular immunoreactivity to PKC isoforms and amino-terminal APP was significantly reduced within the necrotic core. Striking carboxy-terminal APP immunoreactivity was observed in some neurons remaining within the necrotic core. In the boundary of the glutamate lesion, the perikarya of most neurons were intensely immunoreactive to PKC alpha and beta. Furthermore, within the boundary zone, enhanced immunoreactivity within neuronal perikarya was observed to amino-terminal APP and, to a lesser extent, carboxy-terminal APP. Increased immunostaining of PKC alpha and beta and APP at the boundary zone was a consistent feature of intracortical glutamate perfusion and was not observed following NaCl perfusion. There were minimal alterations in PKC isoforms gamma, delta, epsilon, and zeta, in the boundary region following intracortical glutamate or NaCl perfusion. There was no astrocytic response, as detected by GFAP immunoreactivity, at the boundary zone. These findings indicate that there is a topographical relationship between cellular alterations of specific PKC isoforms and APP following an excitotoxic challenge in vivo.
Horsburgh
K
K
Wellcome Surgical Institute and Hugh Fraser Neuroscience Laboratories, University of Glasgow, Bearsden Road, Garscube Estate, Glasow, G61 1QH, United Kingdom.
Mackay
K B
KB
McCulloch
J
J
D016564:Amyloid beta-Protein Precursor / Q000187:drug effects*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D018698:Glutamic Acid / Q000494:pharmacology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D011493:Protein Kinase C / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016564:Amyloid beta-Protein Precursor; D018698:Glutamic Acid; D011493:Protein Kinase C