Neurotrophic factor mRNA expression in dentate gyrus is increased following angular bundle transection

In the central nervous system, the highest levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA are found in the hippocampal formation. In the present study, we report that a unilateral transection of the angular bundle, which relays cortical information via the entorhinal cortex to the hippocampal formation, increases NGF and BDNF mRNA in the ipsilateral dentate gyrus. Within 4 hours following transection, the hybridization signal for NGF and BDNF mRNA increases in stratum granulosum 3- and 5-fold, respectively, compared to control levels. This lesion-induced increase of both mRNA returns to control levels within 24 hours and is maintained for at least 5 days. The induction is not prevented by pretreatment with AP-5, CNQX, or cholinergic denervation due to transection of the fimbria-fornix. Finally, the induction of neurotrophin mRNA is preceded by an increase in c-fos mRNA. These results provide evidence that transection of the cortical input to the hippocampal formation upregulates NGF and BNDF mRNA selectively in stratum granulosum. We suggest that the increased expression of NGF and BDNF mRNA may be an early step in the synaptic rearrangement of neurotrophin responsive cholinergic afferents observed following damage to the entorhinal cortex.