Axotomy-induced loss of m2 muscarinic receptor mRNA in the rat facial motor nucleus precedes a decrease in concentration of muscarinic receptors.

Abstract

The abundance of muscarinic receptors and m2 muscarinic receptor mRNA in the facial nuclei of rats was evaluated by autoradiographic procedures at various times up to 14 days after transection of the right facial nerve. Receptors were labelled by in vitro incubation of brain sections with L-[3H]quinuclidinyl benzilate, while in situ hybridization with a 35S-labelled oligonucleotide was used to identify m2 muscarinic receptor mRNA in neighbouring sections. The right and left facial nuclei of non-operated control rats appeared equivalent in abundance of muscarinic receptors (359 +/- 8 versus 376 +/- 9 fmol per mg tissue, n = 5) and the presence of m2 mRNA. Axotomy had no effect on the concentration of receptors in the contralateral facial nucleus but caused a gradual loss of receptors from the ipsilateral side. No change was detected at 1 day after nerve transection, but a 23% decrease relative to the contralateral facial nucleus had occurred by 3 days. A maximum decrease of 51% was achieved by 1 week after nerve transection. By comparison, m2 mRNA was nearly eliminated from the ipsilateral facial nucleus at 1 day post-taxonomy and remained depleted for the duration of study. Previous work has established that no significant loss of motoneurons occurs within this period. Accordingly, it is postulated that axonal injury inhibits transcription of the m2 muscarinic receptor gene, resulting in a later decrease in muscarinic receptor protein expression.