Effects Of DSS On The Learning And Memory Abilities In Scopolamine-induced KM Mice And Its Possible Mechanism

ObjectiveAlzheimer’s disease (AD), one of the most common neurodegenerative disorders of the central nervous system, greatly threatens the health of the elderly. Although there are many theories and views about the etiology of AD, the precise mechanism remains unknown, and no utility drugs have been developed. So, to develop more effective AD therapeutic drugs with lower toxicity and lower side-effect remains an urgent task.A large number of drugs with differing targets and mechanisms of action are under development for the treatment of AD. But, the sponsor announced its intention to discontinue development of tramiprosate as a pharmaceutical. Aiming to a sole target seemed difficulty to obtain the satisfied therapeutic effects since AD is too complex. Traditional Chinese Medicine (TCM) are composed of many ingredients, they have the characteristics of multi-mechanisms, multi-pathway and multi-targets, which may consistent with AD.Danggui-Shaoyao-San (DSS) is a traditional Chinese Medicinal Prescription. The prescription now still widely used in clinical and the therapeutical effect of DSS on AD was firstly reported at1980’s in Japan. DSS was initially recorded in’Synopsis of Prescriptions of the Golden Chamber’, which was compiled by Zhang-Jing Zhang during the Han dynasty. The prescription was used to relieve menorrhalgia and other abdominal pains of women. The effects of DSS in improving the symptom of mild and moderate AD patients had been confirmed, and DSS could also ameliorate the recognizing ability in many AD model animals, such as models of aging, cerebral ischemia and chemical injury to the brain. Through behavior evaluation and possible mechanism explore, and active component analysis, we hope to explore the possible mechanism of the neuroprotective effects of DSS, which may be develop to a promising new Chinese drug on AD treatment.Methods and Results1. Effects of DSS on the learning and memory in AD model miceIn this part, the effects of JD-30on the learning and memory deficits were examined in AD model mice. We choose Kunming mice which were intraperitoneal injection (ip.) injected with Scopolamine.DSS was dissolved in distilled water at1.6,3.2,6.4g/ml. The mice in drug treated groups were given intragastric administration of DSS (0.1ml/10g body weight) once a day during the test. After2weeks of drug administration, the Morris water-maze test was performed and the drugs given lasted until the whole test was finished.In the Morris water-maze training session, KM mice rapidly learned the location of the platform, but Mod had significant longer escape latency on every test days. This increase was significantly shortened by combination of DSS (3.2,6.4g/kg). Similarly, on the day of the probe trial following the final day of training, latency (the first time that the mice crossed the former plat form) was increased more in Mod than in Con. The latency was decreased by DSS administration, the above results indicate that DSS improves spatial learning and memory deficits.2. Effects of DSS on the level of cholinergic transmitter in scopolamine-induced KM miceThe activities of TchE in hippocampus were investigated by spectrophotometry, and the expressions of ChAT in hippocampus were detected. Compared with model group, the expressions of ChAT were increased significantly, and the activities of TchE were decreased significantly in the DSS group. It suggested that DSS could increase the content of ACh in hippocampus for intelligent-improvement goal in scopolamine-induced KM mice.Conclusion1. DSS has neuroprotective effect in scopolamine-induced KM mice.2. DSS could increase the content of ACh in hippocampus for intelligent-improvement goal in scopolamine-induced KM mice.In summary, DSS is a neuroprotective agent against the damage and senescence by scopolamine, making it a potential therapeutic agent for AD treatment.