Neuroprotection by D-securinine against neurotoxicity induced by beta-amyloid (25-35).
The effects of (+) securinine on behavior and morphological changes after intracerebral ventricle injection of beta-amyloid (25-35) (Abeta(25-35)) in rats were investigated. A single high dose of Abeta(25-35) could impair the spatial cognitive function. The latency of locating the platform was longer in the model group than in the sham-operated group. While chronic administration of D-securinine (40 mg kg(-1)) could significantly shorten the latency. After Morris water maze, the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) were detected. The results showed that D-securinine could decrease the AchE activity significantly and have no effect on ChAT. Meanwhile, immunohistochemistry analysis revealed that D-securinine could reduce the glial inflammatory responses induced by beta-amyloid protein. These results suggest that the effect of D-securinine in improving the cognitive deficits and neurodegeneration in betaAP(25-35)-treated rats may involve direct and indirect actions on targets. The GABA receptor plays a key role in these therapeutic effects and may be helpful in the treatment of Alzheimer's disease.
Lin
Xu
X
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. xul@imm.ac.cn
Jun-Tian
Zhang
Z
D000110:Acetylcholinesterase / Q000378:metabolism; D000470:Alkaloids / Q000737:chemistry / Q000627:therapeutic use*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001381:Azepines / Q000737:chemistry / Q000627:therapeutic use*; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000627:therapeutic use*; D006572:Heterocyclic Compounds, Bridged-Ring; D007150:Immunohistochemistry / Q000379:methods; D007783:Lactones / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000633:toxicity*; D010455:Peptides / Q000138:chemical synthesis / Q000633:toxicity; D010880:Piperidines / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000470:Alkaloids; D016229:Amyloid beta-Peptides; D001381:Azepines; D005904:Glial Fibrillary Acidic Protein; D006576:Heterocyclic Compounds, 4 or More Rings; D006572:Heterocyclic Compounds, Bridged-Ring; D007783:Lactones; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010455:Peptides; D010880:Piperidines; C074636:amyloid beta-protein (25-35); D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; C000785:securinine