title: Nicotinic acetylcholine receptors in neonatal motoneurons are regulated by axotomy: an electrophysiological and immunohistochemical study in human bcl-2 transgenic mice.
abstract: Motoneuron axotomy was exploited as a model system for studying functional and morphological changes caused in motoneuron cell bodies by peripheral axon injury. Rodent facial motoneurons express functional nicotinic acetylcholine receptors. We have determined the effect of neonatal unilateral facial nerve transection on these receptors by using electrophysiological and immunohistochemical techniques. To avoid rapid apoptotic cell death of axotomized motoneurons, the study was done in mice overexpressing the human bcl-2 transgene. Intact motoneurons responded to acetylcholine by generating a rapidly rising inward current, which was insensitive to methyllycaconitine, a selective antagonist of alpha7-containing nicotinic receptors, but was suppressed by dihydro-beta-erythroidine, a broad-spectrum antagonist. This indicates that mouse facial motoneurons possess nicotinic receptors which are probably devoid of the alpha7 subunit. In striking contrast, axotomized motoneurons displayed little or no sensitivity to acetylcholine. Axotomy did not affect the sensitivity of facial motoneurons to the selective glutamate receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxaxolepropionic acid. Immunohistochemical studies revealed that the alpha4 nicotinic receptor subunit was present in intact motoneurons but was undetectable in axotomized motoneurons. By contrast, the beta2 subunit was comparable in intact and axotomized motoneurons. alpha3 immunoreactivity was undetectable, both in intact and in axotomized motoneurons.Thus, mouse facial nicotinic receptors are possibly of the alpha4beta2 type and axotomy interferes negatively with the expression of the alpha4 subunit. By down-regulating nicotinic receptors, peripheral nerve injury may facilitate motoneuron degeneration. Alternatively, nicotinic receptor downregulation and motoneuron degeneration may be independent consequences of peripheral axotomy.
authors.affiliation: Department of Physiology, University Medical Center, CH-1211 4, Geneva, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Zaninetti
authors.forename: M
authors.initials: M
authors.lastname: Dubois-Dauphin
authors.forename: J
authors.initials: J
authors.lastname: Lindstrom
authors.forename: M
authors.initials: M
authors.lastname: Raggenbass
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D019771:Axotomy; D004594:Electrophysiology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D009046:Motor Neurons / Q000378:metabolism* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology; D011950:Receptors, Cholinergic / Q000378:metabolism*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D011950:Receptors, Cholinergic