BRAIN-DERIVED NEUROTROPHIC FACTOR SPARES CHOLINE-ACETYLTRANSFERASE MESSENGER-RNA FOLLOWING AXOTOMY OF MOTOR-NEURONS IN-VIVO

Choline acetyltransferase (ChAT) is a functional and specific marker g ene for neurons such as primary motor neurons that synthesize and rele ase acetylcholine as a neurotransmitter. In adult mammals, transection of the peripheral nerve results in a loss of immunoreactivity for ChA T in the injured motor neurons without affecting their cell number. Us ing a quantitative RNase protection assay, we have investigated dynami c changes in ChAT mRNA levels following axotomy of motor neurons in th e brainstem of adult rats, One week after transection of the left hypo glossal nerve, levels of ChAT mRNA in the ipsilateral side of the hypo glossal motor nucleus decreased dramatically to around 10% when compar ed to the uninjured contralateral side, When cut axons were chronicall y exposed to brain-derived neurotrophic factor (BDNF) for 1 week, ChAT mRNA levels were maintained at 63% of control levels, Thus, BDNF can abrogate the injury-induced loss of ChAT mRNA in mature motor neurons in vivo., In contrast, neither neurotrophin 4/5 nor nerve growth facto r could prevent the decrease in message, This effect of BDNF on ChAT m RNA levels following peripheral injury to motor neurons demonstrates t he existence of regulatory pathways responsive to neurotrophic factors that can ''rescue'' or ''protect'' cholinergic gene expression. (C) 1 997 Wiley-Liss, Inc.