AXOTOMY-INDUCED C-JUN EXPRESSION IN YOUNG MEDIAL SEPTAL NEURONS IS REGULATED BY NERVE GROWTH-FACTOR

In the present study we investigated the axotomy-induced expression of the proto-oncogene c-jun in young rat medial septal neurons and its r egulation by nerve growth factor. First, medial septal neurons were re trogradely labelled by Fast Blue injection into the hippocampus at pos tnatal day 1 (P1). Rats of different developmental ages (P6, P9, P14, P21, P28 and P42) were then subjected to bilateral fimbria-fornix tran section resulting in the axotomy of septohippocampal projection neuron s. After the lesion, c-JUN immunoreactivity was observed in the nuclei of axotomized medial septal neurons of all stags examined, suggesting that c-JUN induction is an age-independent feature of axotomized medi al septal neurons. Double immunolabelling for choline acetyltransferas e and c-JUN or parvalbumin and c-JUN, respectively, revealed that both cholinergic and GABAergic septohippocampal projection neurons express c-JUN after axotomy. In addition, a co-localization of immunostaining for c-JUN and the neuropeptide galanin was found after lesion, as bot h proteins were induced in the same medial septal neurons following fi mbria-fornix transection. Next, the regulation of c-JUN expression in axtomized medial septal neurons was studied in organotypic cultures of the medial septum. Axotomized medial septal neurons in culture did no t express c-JUN in contrast to the in vivo situation. With the concept that nerve growth factor suppresses c-JUN expression, slice cultures of the medial septum were treated with antibodies against nerve growth factor. This treatment caused a dose-dependent increase in c-JUN-posi tive cells in these slice cultures. Simultaneous addition of nerve gro wth. factor and antibodies against nerve growth factor resulted in the reversal of this effect. These data suggest an age-independent induct ion of c-JUN in axotomized medial septal neurons and its regulation by nerve growth factor. (C) 1998 IBRO. Published by Elsevier Science Ltd .