Staurosporine, a protein kinase inhibitor, attenuates basal forebrain-lesion-induced amnesia and cholinergic neuronal deficit.
We have investigated whether administration of staurosporine, which has been reported to induce differentiation in the human neuroblastoma cell in vitro, attenuates amnesia induced by basal forebrain lesion in rats. Multiple dosage of staurosporine at the doses of 0.05 and 0.1 mg/kg (i.p.) attenuated the impaired performance of the water maze task. Moreover, staurosporine (0.1 mg/kg) reversed the decrease of choline acetyltransferase activity in the fronto-parietal cortex. These results suggest that staurosporine attenuates amnesia through reversal of deficits in cholinergic neurons induced by basal forebrain lesion, and that neurotrophic factor-like substances may open the way for novel therapeutic approaches to Alzheimer's disease.
Nabeshima
T
T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Ogawa
S
S
Nishimura
H
H
Fuji
K
K
Kameyama
T
T
Sasaki
Y
Y
D000470:Alkaloids / Q000627:therapeutic use*; D000647:Amnesia / Q000517:prevention & control*; D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D001921:Brain / Q000033:anatomy & histology / Q000201:enzymology; D001930:Brain Injuries / Q000150:complications* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D007051:Ibotenic Acid / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D010275:Parasympathetic Nervous System; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine
D000470:Alkaloids; D007051:Ibotenic Acid; D002795:Choline O-Acetyltransferase; D011493:Protein Kinase C; D019311:Staurosporine