The Machanism Of Ginsenoside Rg₁/Rb₁ Alleviate The Impaired Learning And Memory In Senescence-accelerated Mouse Prone8

Alzheimer's disease(AD) is a progressive neurodegenerative disorder that is characterized by its typical clinical sympotoms, like memory impairment and change in personality. A central role of Aβ(beta amyloid)which contribute to AD pathology have been widely accepted, and recent evidence points out: soluble Aβin brains has marked- ly increased in the early stage of AD, a strong correlation has been established between the levels of soluble Aβand the severity of dementia in humans. Moreover, the higher level of soluble Aβis accompanied by reduced synaptic plasticity, inactivation of PKA (protein kinase A)/CREB signaling pathway, followed by decreased phosphory- lation of CREB, which are critical for learning and memory by modulates transcription of a variety of proteins including BDNF(brain-derived neurotrophic factor).Consequently it is believed that targeting the soluble Aβand impairment of phosphorylation of CREB will ultimately generate novel therapeutics with disease modifying properties in early phase of AD. Ginsenoside Rg1/Rb1 are two of representative monosomic ginsenoside extract from ginseng. They have been proved to alleviate the impairment of learning and memory in defferent anmimal models for AD, abolish the multiple neurotoxicity induced by Aβ. And they have great potential value for the treatment of AD.We choose SAMP8(senescence-accelerated mouse Prone8,SAMP8) as model of sporadic AD in early stage, due to plenty of neuropathology in SAMP8,including remarkly higher level of soluble Aβand impairment of CREB phosphorylation in the brains, accompanied with a spontaneous significant age-related deterioration in learning and memory. Thus the present study included three sections, aimed at investigating the alleviation of Ginsenoside Rg1/Rb1 to deficit of learning and memory in SAMP8 and and exploring the molecular mechanisms targeting in Aβ, PKA/CREB signaling pathway and BDNF. The results were showed as follows:In the Part One, 2.5,5,10mg/Kg Rg1/Rb1 were injected daily to male SAMP8 6 months old for 3 months, Ginsenoside Rg1/Rb1 alleviate the impaired learning and memory of SAMP8 in Y-maze and step down test, effect were optimal for 10mg/Kg Rg1 or 5mg/Kg Rb1 respectively.In the Part Two, It was confirmed that there were significantly higher soluble Aβ1-40 in the brains of SAMP8 than SAMR1, and Ginsenoside Rg1/Rb1 both decreased the level of Aβ1-40.In the Part Three, The impairment of CREB phosphorylation in hippocampus of SAMP8 was proved versus SAMR1 after behavioral experiment., accompanied by incresed protein levels of PKAIIαand decline of BDNF, all of which were reversed by Ginsenoside Rg1/Rb1.To summarize, Ginsenoside Rg1/Rb1 can alleviate the impaired learning and memory in SAMP8 , probably due to decrease the level of Aβ1-40 and increase the phosphorylation of CREB and protein level of BDNF by PKA/CREB signaling pathway.In addition, the dose-response curves of Rg1 and Rb1were different, may be due to the different optimal dosages between them or other machanism involved in the pharmacology effect of Rb1.