Abstract
Background:
It is well known that Alzheimer's disease (AD) is a degenerative disease, and accompanied by memory impairment and main pathological changes of the extracellular senile plaque (SP) and intracellular neurofibrillary tangles (NFTs). However, there are many evidences showing that the disorders of neurogenesis are also regarded as a new opinion in AD.
Objective:
To investigate the effects and regulative mechanism of Scutellaria baicalensis Georgi stems and leaves flavonoids in promoting neurogenesis and improving memory impairment mediated by BDNF-ERK-CREB signal pathway in rats.
Methods:
Male Wistar rats were intracerebroventricularly injected with amyloid-beta protein 25-35 (Aβ25-35) in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1 (RHTGF-β1) (composited Aβ), to establish an AD model. Morris water maze was used to screen AD model of rats and measure the rats' learning and memory ability. The expression of cell neurogenesis related molecule Ki67 protein in the hippocampal gyrus of rats was detected by the immunohistochemical method. The expression of mRNA and protein of Grb2, SOS1, Ras, ERK and BDNF in the BDNF-ERK-CREB signaling pathway, in the hippocampus and cerebral cortex were assayed by the Quantitative real-time PCR (qPCR) and Western blotting methods, respectively.
Results:
Intracerebroventricular injection of composited Aβ could produce the rats' memory impairment, decrease the protein expression of Ki67 in the hippocampal gyrus, and increase the mRNA and protein expression levels of Grb2, SOS1, Ras, ERK and BDNF in the hippocampus and cerebral cortex. However, SSF could significantly ameliorate the rats' memory impairment, lower the reduction of Ki67 protein expression in the hippocampal gyrus and regulate the mRNA and protein expression abnormal levels of Grb2, SOS1, Ras, ERK and BDNF in the hippocampus and cerebral cortex induced by composited Aβ.
Conclusion:
Composited Aβ can result in memory impairment, decrease neurogenesis and regulate the mRNA and protein abnormal expression of Grb2, SOS1, Ras, ERK and BDNF in BDNF-ERK-CREB signaling pathway. The effects of SSF in promoting neurogenesis and improving memory impairment may be related to the regulation in Grb2, SOS1, Ras, ERK and BDNF molecules' expression of the BDNF-ERK-CREB signaling pathway.
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