Effects of nefiracetam on cerebral adenylyl cyclase activity in rats with microsphere embolism-induced memory dysfunction.
The effects of nefiracetam on the cerebral adenylyl cyclase (AC) activity of animals with microsphere embolism-induced memory dysfunction were examined. Sustained cerebral ischemia in the right cerebral hemisphere was induced by an injection of microspheres into the right internal carotid artery of rats. To examine learning and memory function, the water maze test was performed from day 7 to day 10 after the operation. The escape latency of the microsphere-embolized (ME) rat in the water maze task was longer than that of the sham-operated (Sham) rat, suggesting that spatial memory dysfunction occurred in the ME rat. Gsalpha and Gi(1/2)alpha protein levels in the cerebral cortex, striatum and hippocampus of the ME rat, when determined on day 11, were similar to those of the Sham rats. The basal AC activity in the striatum, but not in the other two regions, of the ME rat decreased. The AC activity in the presence of 10 microM colforsin daropate (Col), a direct stimulator of AC, was increased by approximately 20-fold in sham animals and 7- to 10-fold in the ME rat. Treatment of the ME rat with 10 mg/kg/d nefiracetam p.o. from day 1 to day 10 after the operation shortened the escape latency, restored the basal AC activity in the striatum, and reversed the Col-induced increases in AC in these three regions without any changes in the cerebral Gsalpha and Gi(1/2)alpha protein levels. These results suggest that nefiracetam-mediated activation of AC activity may contribute to the improvement of memory and learning function in sustained cerebral ischemia.
Takeo
Satoshi
S
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Japan. takeos@ps.toyaku.ac.jp
Miyake-Takagi
Keiko
K
Kikuchi
Kanako
K
Ando
Tsuyoshi
T
Ichikawa
Tomonaga
T
Omino
Kunio
K
Kajihara
Hiroshi
H
Takagi
Norio
N
Tanonaka
Kouichi
K
D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004617:Embolism / Q000150:complications*; D004924:Escape Reaction / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D008863:Microspheres; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011760:Pyrrolidinones / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018696:Neuroprotective Agents; D011760:Pyrrolidinones; C122001:colforsin daropate; D005576:Colforsin; C058876:nefiracetam; D000242:Cyclic AMP; D019204:GTP-Binding Proteins