Effect of α-asarone on ethanol-induced learning and memory impairment in mice and its underlying mechanism

OBJECTIVE To investigate the effect ofα-asarone on ethanol-impaired cognitive ability and explore the underlying mechanism in mice. METHODS A mouse model of impaired learning and memory was created by ethanol(2.0 g · kg~(-1), ig). α-Asarone(7.5, 15 and 30 mg·kg~(-1), ip) was delivered 10 min prior to ethanol administration. After 40 min, the locomotor activity of mice with learning and memory impairment was evaluated by the open field test and the behavioral effect of α-asarone was evaluated using the novel object recognition test.Glutamate(Glu) and γ-aminobutyric acid(GABA) levels in the hippocampus were determined by ELISA, and the proteins expression levels of hippocampal α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid(AMPA) receptor(Glu R2), N-methyl-D-aspartic acid(NMDA)receptor(NMDAR2 B), synaptophysin I(SYNΙ), glutamate transporter type 1(GLT-1) and calcium/calmodulindependent protein kinaseⅡ(Ca MKⅡ) were detected by Western blotting. RESULTS There was no significant difference in the horizontal or vertical locomotor activity between the ethanol and normal groups or the 7.5, 15 and 30 mg·kg~(-1)α-asarone groups[F(5, 48)=0.6536, P>0.05; F(5, 49)=1.995, P>0.05]. The recognition index in the ethanol group was significantly decreased as compared with that in the normal group[F(5, 46) =6.739, P<0.05]and was markedly increased in the α-asarone groups as compared with that in the ethanol group(P<0.05), with the exception of the 7.5 mg · kg~(-1)α-asarone group(P>0.05). The hippocampal Glu: GABA ratio in mice was significantly elevated in the ethanol group as compared with that in the normal group(33.42±0.8972 vs 30.79±0.2102, P<0.05) and significantly lower in the α-asarone groups(31.99±0.4986 vs. 33.42±0.8972; 30.97±0.1757 vs. 33.42±0.8972; 30.83 0.1723 vs. 33.42±0.8972, P<0.05). The expression levels of GluR2, NMDAR2B, pSYNⅠand p Ca MKII were significantly higher in the ethanol group as compared with those in the normal group(P<0.05) and obviously lower in the α-asarone groups(P<0.05), with the exception of GluR2, NMDAR2B and pCaMKⅡ in the 7.5 mg·kg~(-1)α-asarone group(P>0.05).And the expression level of GLT-1 was significantly lower in the ethanol group as compared with that in the normal group(P<0.05) and obviously higher in the α-asarone groups(P<0.05). CONCLUSION Pretreatment with α-asarone significantly improved the learning and memory impairment. A possible underlying mechanism is regulation of the calcium signaling cascade to correct functioning of related proteins, and thus, maintain the level of Glu.