CHOLINERGIC SPROUTING IN THE RAT FASCIA-DENTATA AFTER ENTORHINAL LESION IS NOT LINKED TO EARLY CHANGES IN NEUROTROPHIN MESSENGER-RNA EXPRESSION

After unilateral entorhinal cortex lesion cholinergic septohippocampal fibres sprout in the denervated fascia dentata. This process is depen dent on neurotrophin changes following the lesion. Thus, there is an u p-regulation of nerve growth factor and brain-derived neurotrophic fac tor messenger RNA expression in the denervated granule cells which is delectable 4 h postlesion and returns to control levels by 24 h. Here, using a competitive polymerase chain reaction and in situ hybridizati on, a transient neurotrophin messenger RNA increase could be demonstra ted bilaterally following unilateral electrolytic entorhinal cortex le sion. Treatment of the animals with the N-methyl-D-aspartate receptor antagonist dizocilpine maleate blocked this messenger RNA increase, su ggesting an involvement of this receptor IS pe in the neurotrophin cha nges. However, in spite of this blockade, the typical cholinergic spro uting response as visualized with acetylcholinesterase histochemistry was present in animals four weeks after entorhinal cortex lesion. Thes e data suggest that brief initial changes in neurotrophin messenger RN A expression in dentate granule cells are not responsible for the indu ction of the cholinergic sprouting. Changes in neurotrophin messenger RNA expression occurring immediately postlesion may be linked to gluta mate release from entorhinal terminals resulting from the electrolytic lesion of the projection cells in the entorhinal cortex. We hypothesi ze that later changes in neurotrophin expression, for example in glial cells, are more likely to be related to the cholinergic sprouting pro cess. (C) 1997 IBRO. Published by Elsevier Science Ltd.