Staurosporine facilitates recovery from the basal forebrain-lesion-induced impairment of learning and deficit of cholinergic neuron in rats.
Alzheimer's disease is characterized by the loss of cholinergic neurons in the nucleus basalis of Meynert and by a primary loss of memory function. Since staurosporine has been reported to induce differentiation in human neuroblastoma cells in vitro, we studied the effects of staurosporine on the amnesia induced by basal forebrain-lesion in rats. Staurosporine (0.05 and 0.1 mg/kg intraperitoneal) attenuated the impaired performance of water maze and passive avoidance tasks, even though the drug administration began 2 weeks after the lesion. Moreover, staurosporine (0.1 mg/kg) partially reversed the decrease of choline acetyltransferase activity in the fronto-parietal cortex induced by basal forebrain-lesion. These results suggest that staurosporine attenuates impairment of learning through reversal of damage to cholinergic neurons induced by basal forebrain-lesion. This evidence indicates that neurotrophic factor-like substances may be used in 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 / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001479:Basal Ganglia / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D007051:Ibotenic Acid; D008297:Male; 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