Effects of nefiracetam on the levels of brain-derived neurotrophic factor and synapsin I mRNA and protein in the hippocampus of microsphere-embolized rats.
Our recent study demonstrated that nefiracetam, N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, prevented impairment of the cyclic AMP (cAMP)/cAMP-responsive element binding (CREB) protein signaling pathway in sustained cerebral ischemia. The purpose of the present study was to determine whether nefiracetam has an effect on the expression of brain-derived neurotrophic factor (BDNF) and synapsin I mRNAs that are believed to be produced via CREB, and the alteration in their protein contents in the hippocampus after cerebral ischemia. Sustained cerebral ischemia was induced by injection of 700 microspheres into the right hemisphere of each rat. The rats were treated once daily with 10 mg/kg nefiracetam, p.o., from 15 h after the operation. Treatment with nefiracetam reduced the prolongation of the escape latency in the water maze test on days 7-9 after microsphere embolism-induced sustained cerebral ischemia, suggesting an improvement in the spatial learning function. Microsphere-embolized rats on day 5 showed decreases in BDNF and synapsin I mRNA levels and their protein contents in the ipsilateral hippocampus. Treatment with nefiracetam partially attenuated the decreases. These results suggest that enhancement of BDNF and synapsin I expression by nefiracetam treatment may be, at least in part, due to the improvement in the CREB binding activity, contributing to the prevention of learning and memory dysfunction after sustained cerebral ischemia.
Ando
Tsuyoshi
T
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Takagi
Norio
N
Takagi
Keiko
K
Kago
Tomoyuki
T
Takeo
Satoshi
S
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D020766:Intracranial Embolism / Q000378:metabolism*; D008297:Male; D008863:Microspheres; D011760:Pyrrolidinones / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D016704:Synapsins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D011760:Pyrrolidinones; D012333:RNA, Messenger; D016704:Synapsins; C058876:nefiracetam