AGE-RELATED-CHANGES OF CHOLINERGIC MARKERS IN THE RAT-BRAIN

To evaluate whether any degenerative changes affect the brain choliner gic systems during natural aging, we compared various cholinergic bioc hemical markers (number of muscarinic receptors, mAChR; choline acetyl transferase activity, ChAT; acetylcholinesterase activity, AChE; and s odium-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 [H-3]-quinuclidinyl benzilate ([H-3]-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 i n young rats, while a significant age-related increase in the affinity of mAChR was observed. [H-3]-QNB binding in both the young and aged r at brain was displaced markedly by pirenzepine, while [H-3]-QNB bindin g in the SS of the aged rat brain was displaced at low concentrations of atropine. The V-max values of ChAT and AChE also decreased about 20 -30% compared with those of young rats. The sodium-dependent high affi nity choline uptake was lower in the crude synaptosomal fraction prepa red from aged rat brain than in young brain. Hemicholinium-3 inhibited the choline uptake in young rat brain at a concentration range of 1 m u M-10 nM, but choline uptake in aged brain was insensitive to hemicho linium-3. These results indicate that natural aging brings about a dif fuse and multiple depletion of various biochemical markers in choliner gic neurons.