Aging and subcellular localization of m2 muscarinic autoreceptor in basalocortical neurons in vivo.
By using immunohistochemical approaches at the light and electron microscopic levels, we have shown that aging modifies the subcellular distribution of the m2 muscarinic autoreceptor (m2R) differentially at somato-dendritic postsynaptic sites and at axonal presynaptic sites in cholinergic basalocortical neurons, in vivo. In cholinergic perikarya and dendrites of the nucleus basalis magnocellularis (NBM), aging is associated with a decrease of the density of m2R at the plasma membrane and in the cytoplasm, suggesting a decrease of the total number of m2R in the somato-dendritic field. In contrast, the number of substance P receptors per somato-dendritic surface was not affected. In the frontal cortex (FC), we have shown a decrease of cytoplasmic m2R density also leading to a decrease of the number of m2R per surface of varicosities but with no change of the density of m2R at the membrane. Our results suggest that the decrease of m2R in the somato-dendritic field of the NBM, but not a modification of the number of presynaptic m2 autoreceptors at the plasma membrane in the FC, could contribute to the decrease of the efficacy of cholinergic transmission observed with aging in the rat.
Décossas
Marion
M
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5541, Laboratoire d'Histologie-Embryologie, Université Victor Ségalen-Bordeaux 2, 146 rue Léo-Saignat, 33076 Bordeaux Cedex, France.
Doudnikoff
Evelyne
E
Bloch
Bertrand
B
Bernard
Véronique
V
D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000166:cytology* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D005625:Frontal Lobe / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D016253:Microscopy, Immunoelectron / Q000379:methods; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D015388:Organelles / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2 / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins
D026901:Membrane Transport Proteins; D043585:Receptor, Muscarinic M2; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D002795:Choline O-Acetyltransferase