INTRACORTICAL PERFUSION OF GLUTAMATE IN-VIVO INDUCES ALTERATIONS OF TAU-ASSOCIATED AND MICROTUBULE-ASSOCIATED PROTEIN-2 IMMUNOREACTIVITY INTHE RAT

Modifications of microtubule-associated proteins (MAP) have been repor ted in both acute and chronic degenerative conditions, such as cerebra l ischaemia and Alzheimer's disease, and may be associated with cytosk eletal 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 extracell ular glutamate concentrations on the distribution of tau and MAP2 in v ivo in order to determine whether glutamate induces similar changes in tau to those previously reported in vitro in the intact, adult centra l nervous system. Monosodium glutamate was perfused into the rat parie tal 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 agai nst full-length tau or towards the N or C termini of the protein. In c ontrast, increased tau immunoreactivity was detected, with all the ant ibodies used in this study, within oligodendrocytes following either g lutamate or sodium chloride perfusion. MAP2 immunoreactivity was incre ased within perikarya at the core of the glutamate-induced lesion, whi le dendritic immunoreactivity was reduced. These results suggest that glutamate excitotoxicity in vivo may not be involved in neurofibrillar y tangle formation but may be important in the progression of cytoskel etal pathology following cerebral ischaemia.