Age-related changes of cholinergic markers in the rat brain

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.