No abstract

The effects of aged garlic extract (AGE) on longevity and learning and memory performances were studied in the senescence accelerated mouse (SAM). A solid diet containing 2% (w/w) AGE was given to SAM from 2 months of age. The survival ratio of SAM P8, senescence accelerated animals, treated with AGE was significantly higher than that of untreated controls. AGE, however, did not affect the life span of SAM R1, a senescence-resistant strain. AGE had no effect on body weight and motor activity. In the passive and conditioned avoidance tests, AGE markably improved a memory acquisition process in the step-down and shuttle-box tests, and also a retention process in the step-through and step-down tests in SAM P8. The beneficial effects of AGE were observed in a memory retention process in the step-down test and in an acquisition stage in lever-press test in SAM R1. These results suggest the possibility that AGE might be useful for treating physiological aging and age-related memory deficits in humans.

The acute effects of DX-9386, a traditional Chinese medicinal preparation (ginseng, polygala, acorus and hoelen), were studied on learning and memory performances in passive and active avoidance tests in normal, as well as in learning-impaired, mice. A single oral administration of the prescription had no effect on memory registration, consolidation or retrieval or on motor activity in normal mice. DX-9386 reduced the ethanol-induced impairment of memory registration in the step-down test and also tended to ameliorate the scopolamine-induced memory registration deficit in the same test. The preparation reduced the number of spontaneous responses in the active avoidance test. The preparation also prolonged the disappearance of righting reflex induced by pentobarbital. These results suggest that DX-9386 ameliorates the impairment effect of ethanol on learning and memory processes and also exhibits a sedative effect.

MKC-231, a putative cholinergic activity, is reported to improve learning and memory impaired in AF64A-treated animals. MKC-231 enhances high-affinity choline uptake (HACU) known as the rate-limiting step of acetylcholine (ACh) synthesis. We investigated the mode of action (MOA) of HACU enhancement by MKC-231. Intracerebroventricular (i.c.v.) injections of AF64A (3 nmol/brain) resulted in significant HACU reduction in hippocampal synaptosomes. Treatment with MKC-231 increased Vmax of HACU and Bmax of [3H]-HC-3 binding 1.6 and 1.7-fold, respectively. In studies of [3H]-MKC-231 binding and Biacore analysis, MKC-231 showed noticeable affinity for cloned high-affinity choline transporters (CHT1). The present study suggests that MKC-231 directly affects trafficking of CHT1 and increases the numbers of transporter, working for HACU, at the synaptic membrane.

The effects of DX-9386, a traditional Chinese prescription (ginseng, acorus, polygala and hoelen) were studied on life span, the degree of senescence, motor activity and the antibody production response in senescence accelerated mouse (SAM). DX-9386-containing food was given to SAM for 13 consecutive months from 2 months of age. DX-9386 significantly prolonged the life span of SAM, prevented body weight decrease with aging and tended to improve the senile syndrome. The motor activity of SAMP8 was higher than that of SAMR1, and DX-9386 tended to increase the activity in SAMP8. The in vivo antibody production was markedly decreased in SAMP8 and DX-9386 showed no ameliorating effect on that. These results suggest that DX-9386 has anti-aging impact.