title: Age-related changes of cholinergic markers in the rat brain.
abstract: To evaluate whether any degenerative changes affect the brain cholinergic systems during natural aging, we compared various cholinergic biochemical markers (number of muscarinic receptors, mAChR; choline acetyltransferase activity, ChAT; acetylcholinesterase activity, AChE; and sodium-dependent high affinity  choline uptake) in the cortical (CR) and subcortical (SS) regions of the brains of aged (24 month) and young (2 month) rats. Using [3H]-quinuclidinyl benzilate ([3H]-QNB) as the ligand of muscarinic receptor binding, the numbers of mAChR decreased about 30% in both the CR and the SS of aged rats compared with those in young rats, while a significant age-related increase in the affinity of mAChR was observed. [3H]-QNB binding in both the young and aged rat brain was displaced markedly by pirenzepine, while [3H]-QNB binding in the SS of the aged rat brain was displaced at low concentrations of atropine. The Vmax values of ChAT and AChE also decreased about 20-30% compared with those of young rats. The sodium-dependent high affinity choline uptake was lower in the crude synaptosomal fraction prepared from aged rat brain than in young brain. Hemicholinium-3 inhibited the choline uptake in young rat brain at a concentration range of 1 microM-10 nM, but choline uptake in aged brain was insensitive to hemicholinium-3. These results indicate that natural aging brings about a diffuse and multiple depletion of various biochemical markers in cholinergic neurons.
authors.affiliation: Department of Pharmacology, Oita Medical University, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Yufu
authors.forename: T
authors.initials: T
authors.lastname: Egashira
authors.forename: Y
authors.initials: Y
authors.lastname: Yamanaka
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001667:Binding, Competitive; D015415:Biomarkers; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D006426:Hemicholinium 3 / Q000494:pharmacology; D008297:Male; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D011976:Receptors, Muscarinic; D006426:Hemicholinium 3; D011813:Quinuclidinyl Benzilate; D012964:Sodium; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002794:Choline