EFFECTS OF INTRAHIPPOCAMPAL COLCHICINE ADMINISTRATION ON THE LEVELS AND LOCALIZATION OF MICROTUBULE-ASSOCIATED PROTEINS, TAU AND MAP2

Colchicine, a microtubule disrupting agent, has been used to model sev eral aspects of Alzheimer's disease-related neuropathology. The format ion of neurofibrillary tangles, one of the pathological hallmarks of A lzheimer's disease, involves the loss of tau (a low mol. wt. microtubu le-associated protein) from axons and accumulation of abnormally phosp horylated tau in somatodendritic compartments. Other cytoskeletal prot eins, such as microtubule-associated protein 2 (MAP2), disappear as ta u accumulates. The present study was directed at evaluating the effect s of colchicine on tau and MAP2, to determine if changes in their leve ls or distribution might be similar to those which precede the formati on of neurofibrillary tangles in Alzheimer's disease. Six hours follow ing intrahippocampal colchicine injection (3.5 mu g injected into two rostro-caudal locations) tau-l immunostaining was enhanced in CA1 s. r adiatum and decreased in the outer molecular layer of the dentate gyru s. In addition, a shift in the relative abundance of tau isoforms was observed in Western blots. Both the immunocytochemical and immunoblot results are consistent with a dephosphorylation of tau. Loss of MAP2 w as evident 3 days postinjection which coincided with a loss of Cresyl violet staining in granule cell, CA3, subicular and entorhinal neurons . Accumulation of tau or MAP2 in neuronal perikarya was not observed a t any postinjection time points. Thus, intrahippocampal colchicine adm inistration does not model the shift in tau localization, excessive ta u phosphorylation, or other cytoskeletal alterations that are suggeste d to precede or accompany the formation of neurofibrillary pathology i n Alzheimer's disease.