OBJECTIVETo provide a useful biological index for clinical diagnosis of Alzheimer's disease (AD) by determination the functional changes in the central cholinergic nerve and their effects on the peripheral lymphatic system.

METHODSThe learning and memory impairment model was established through intraventricular injecting quinolinic acid (QA) repeatedly.

RESULTSThere was a significant decline of cholineacetyltransferase (ChAT) in cerebral cortex and hippocampus after QA injection. The significantly lower binding activities of acetylcholine muscarinic (M) and nicotinic (N) cholinergic receptors in the hippocampus and cortex in the QA group were found as compared with the sham-operated group (P < 0.01). Similar changes were found in the binding activities of M-and N-receptors on spleen lymphocytes.

CONCLUSIONCertain lesion of the central nervous system can be reflected in peripheral spleen lymphocytes, which may be an important reference to diagnose the changes of the central nervous system.

Alzheimer Disease ; etiology ; Animals ; Brain ; drug effects ; Choline O-Acetyltransferase ; metabolism ; Disease Models, Animal ; Learning ; drug effects ; Male ; Memory ; drug effects ; Nicotine ; metabolism ; Quinolinic Acid ; toxicity ; Quinuclidinyl Benzilate ; metabolism ; Rats ; Rats, Wistar ; Receptors, Cholinergic ; analysis ; drug effects

OBJECTIVETo investigate the changes of spontaneous and cognitive behavior, and cholinergic M receptors in the brain of mice subjected to chronic mild stress (CMS), and to determine the effect of Ning Shen Ling Granule (NSL) and dehydroepiandrosterone (DHEA) on them.

METHODSCMS model mice were established by applying stress every day for 3 consecutive weeks with 7 kinds of unforeseeable stress sources, and they were medicated for 1 week beginning at the 3rd week of modeling. The changes in behavior were determined by Morris Water Maze and spontaneous movement test, and M-receptor binding activity in cerebral cortex, hippocampus and hypothalamus were measured by radioactive ligand assay with 3H-QNB.

RESULTS(1) The spontaneous movement in CMS model mice was significantly reduced, with the latency for searching platform in Morris Water Maze obviously prolonged (P<0.01), and these abnormal changes in behavior were improved in those treated with NSL and DHEA. (2) The binding ability of M-receptor in cerebral cortex and hippocampus of CMS mice was significantly decreased as compared with those in the control group (P<0.05), but could be restored to the normal level after intervention with NSL or DHEA.

CONCLUSIONThe decline of spontaneous movement and spatial learning and memory ability could be induced in animals by chronic mild stress, and that may be related to the low activity of central cholinergic M-receptors. Both NSL and DHEA could effectively alleviate the above-mentioned changes.

Animals ; Cerebral Cortex ; metabolism ; Chronic Disease ; Cognition ; drug effects ; Dehydroepiandrosterone ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Mice ; Mice, Inbred Strains ; Movement ; drug effects ; Quinuclidinyl Benzilate ; metabolism ; Receptors, Muscarinic ; metabolism ; Severity of Illness Index ; Stress, Physiological ; metabolism ; physiopathology ; psychology ; Swimming