RESUMO
In aging individuals, age-related cognitive decline is the most common cause of memory impairment. Among the remedies, ginsenoside Rg1, a major active component of ginseng, is often recommended for its antiaging effects. However, its role in improving cognitive decline during normal aging remains unknown and its molecular mechanism partially understood. This study employed a scheme of Rg1 supplementation for female C57BL/6J mice, which started at the age of 12 months and ended at 24 months, to investigate the effects of Rg1 supplementation on the cognitive performance. We found that Rg1 supplementation improved the performance of aged mice in behavior test and significantly upregulated the expression of synaptic plasticity-associated proteins in hippocampus, including synaptophysin, N-methyl-D-aspartate receptor subunit 1, postsynaptic density-95, and calcium/calmodulin-dependent protein kinase II alpha, via promoting mammalian target of rapamycin pathway activation. These data provide further support for Rg1 treatment of cognitive degeneration during aging.
Assuntos
Fármacos do Sistema Nervoso Central/uso terapêutico , Cognição/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Ginsenosídeos/uso terapêutico , Plasticidade Neuronal/efeitos dos fármacos , Panax , Sinapses/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Suplementos Nutricionais , Proteína 4 Homóloga a Disks-Large , Feminino , Guanilato Quinases/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Proteínas de Membrana/efeitos dos fármacos , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Microscopia Eletrônica de Transmissão , Distribuição Aleatória , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Comportamento Espacial/efeitos dos fármacos , Sinapses/ultraestrutura , Sinaptofisina/efeitos dos fármacos , Serina-Treonina Quinases TOR/efeitos dos fármacosRESUMO
OBJECTIVE: To explore the effects of aging on the levels of reproduction-related mRNA genes including Gnrh, KISS1/KISS1r, estrogen receptor-alpha (ERα), estrogen receptor-beta (ERß) and progesterone receptor (PR) in hypothalamus. METHODS: Proestrus and metestrus in young (3-4 months) and middle-aged (10-11 months) female mice and diestrus in senile (18-19 months) female mice were observed. And the levels of related mRNA genes in preoptic area anterior hypothalamus (POA-AH) and medial basal hypothalamus (MBH) were determined by real-time polymerase chain reaction (RT-PCR). RESULTS: In middle-aged mice on proestrus, the level of Gnrh mRNA in POA-AH (0.896 ± 0.049) was significantly lower than that in young mice (1.228 ± 0.147, P = 0.049). The level of ERα mRNA in POA-AH decreased in young mice on proestrus whereas increased in middle-aged mice (0.432 ± 0.063 vs 0.603 ± 0.018, P = 0.016). The level of ERα mRNA of POA-AH, both in middle-aged mice (0.432 ± 0.063, P = 0.014) and senile mice (0.403 ± 0.145, P = 0.020) on diestrus, were significantly lower than that in young mice. The PR mRNA expression in middle-aged mice on proestrus (1.037 ± 0.037) was markedly lower than that in young mice (1.251 ± 0.081, P = 0.031) . In senile mice, the levels of Gnrh mRNA (1.520 ± 0.146, P = 0.004) and ERß mRNA (1.572 ± 0.184, P = 0.011) increased in POA-AH compared with that in young mice on metestrus. Aging had no effect upon KISS1 and KISS1r mRNA levels in POA-AH. In contrast, KISS1 mRNA level of MBH in middle-aged (1.663 ± 0.398, P = 0.037) and senile (2.622 ± 0.454, P = 0.014) mice obviously increased compared with the young mice group. CONCLUSION: Higher levels of ERα mRNA and decreases of PR and Gnrh mRNA in POA-AH in middle-aged mice on proestrus may play an important role in declining reproductive function.