Long-term evolution of local, proximal and remote astrocyte responses after diverse nucleus basalis lesioning (an experimental Alzheimer model): GFAPimmunocytochemical study

A study on long-term astrocytic responses (from 1 day to 20 months after le sioning in 4-month-old rats, and from 1 day to 6 months in 20-month-old rat s) to diverse unilateral damage of the nucleus basalis (nbM) by injection o f 40 nmol of ibotenic acid, or 50 or 100 nmols of quisqualic acid was perfo rmed using a histochemical method (immunoreactivity against the glial fibri llary acidic protein GFAP). Glial reactivity (i.e., isolated or clustered h ypertrophic and/or hyper-reactive astrocytes) was evaluated in several ipsi lateral and contralateral brain regions: the 'local response' within the da maged nbM region; the 'proximal response' (a new concept proposed by us) in the non-damaged structures neighbouring the nbM; and the 'remote response' in the ipsilateral brain cortex and in the contralateral cortex and nbM. I n 4-month-old animals, the remote cortical glial responses, independent of the involution of cortical cholinergic activity and randomly located in lay ers I-V of motor and somatosensory cortical regions, were similar in appear ance over a long period (13-20 months), with the highest reactivity 45 days after lesioning. The proximal response lasted from 1 day to 13 months and afterwards tended to disappear. Contralateral reactivity and ipsilateral co rtical scars were observed. The local (nbM) glial response was maintained t hroughout the period studied. Subsets of astrocytes of different reactiviti es were observed, most of their elements being highly intermeshed. In 20-mo nth-old animals, nbM lesions produced less positive, but similar, glial rea ctive patterns. This glial reactivity was superposed onto the glial reactiv ity of old age. All these results are discussed. The maintenance of reactiv e astrocytes many months after lesioning suggests the existence of cellular factors other than those produced by damaged nbM neurons. Taking into acco unt the role of glial cells under pathological conditions, it is possible t hat these reactive astrocytes in humans could promote neurodegenerative pro cesses, such as amyloid plaque formation and neurodegeneration (Alzheimer's disease). Along this line, nbM cholinergic involution could then originate cortical involution through induced reactive astrocytosis. (C) 2000 Elsevi er Science B.V. All rights reserved.