Intracortical perfusion of glutamate in vivo induces alterations of tau and microtubule-associated protein 2 immunoreactivity in the rat.
Modifications of microtubule-associated proteins (MAP) have been reported in both acute and chronic degenerative conditions, such as cerebral ischaemia and Alzheimer's disease, and may be associated with cytoskeletal breakdown. Glutamate excitotoxicity has been implicated in the pathogenesis of both of these conditions and has been shown in some in vitro studies to induce changes in tau similar to those occurring in Alzheimer's disease. This study examines the effects of high extracellular glutamate concentrations on the distribution of tau and MAP2 in vivo in order to determine whether glutamate induces similar changes in tau to those previously reported in vitro in the intact, adult central nervous system. Monosodium glutamate was perfused into the rat parietal cortex for 90 min using in vivo microdialysis and at 4 h after the start of perfusion the distribution of tau and MAP2 was determined by immunohistochemistry. At the core of the glutamate-induced lesion tau immunostaining, as detected with the Tau 1 antibody, was decreased in axons and increased within perikarya compared to controls. Increased immunostaining was not apparent with polyclonal antibodies raised against full-length tau or towards the N or C termini of the protein. In contrast, increased tau immunoreactivity was detected, with all the antibodies used in this study, within oligodendrocytes following either glutamate or sodium chloride perfusion. MAP2 immunoreactivity was increased within perikarya at the core of the glutamate-induced lesion, while dendritic immunoreactivity was reduced. These results suggest that glutamate excitotoxicity in vivo may not be involved in neurofibrillary tangle formation but may be important in the progression of cytoskeletal pathology following cerebral ischaemia.
Irving
E A
EA
Wellcome Surgical Institute, University of Glasgow, UK.
McCulloch
J
J
Dewar
D
D
D000818:Animals; D010478:Chemotherapy, Cancer, Regional Perfusion; D004333:Drug Administration Routes; D018698:Glutamic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D007278:Injections, Spinal; D008297:Male; D008869:Microtubule-Associated Proteins / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000187:drug effects* / Q000276:immunology
D008869:Microtubule-Associated Proteins; D016875:tau Proteins; D018698:Glutamic Acid