Brain-derived neurotrophic factor spares choline acetyltransferase mRNA following axotomy of motor neurons in vivo.
Choline acetyltransferase (ChAT) is a functional and specific marker gene for neurons such as primary motor neurons that synthesize and release acetylcholine as a neurotransmitter. In adult mammals, transection of the peripheral nerve results in a loss of immunoreactivity for ChAT in the injured motor neurons without affecting their cell number. Using a quantitative RNase protection assay, we have investigated dynamic changes in ChAT mRNA levels following axotomy of motor neurons in the brainstem of adult rats. One week after transection of the left hypoglossal nerve, levels of ChAT mRNA in the ipsilateral side of the hypoglossal motor nucleus decreased dramatically to around 10% when compared to the uninjured contralateral side. When cut axons were chronically 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 factor could prevent the decrease in message. This effect of BDNF on ChAT mRNA levels following peripheral injury to motor neurons demonstrates the existence of regulatory pathways responsive to neurotrophic factors that can "rescue" or "protect" cholinergic gene expression.
Wang
W
W
Division of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
Salvaterra
P M
PM
Loera
S
S
Chiu
A Y
AY
D000818:Animals; D001369:Axons / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010735:Phosphoglycerate Kinase / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D002795:Choline O-Acetyltransferase; D010735:Phosphoglycerate Kinase