Affiliation:
1. Institute of Traditional Chinese Medicine, Chengde Medical College, Chengde 067000, PR China
Abstract
Background:
It is well known that Alzheimer's Disease (AD) is a neurodegenerative disease
accompanied by memory impairment and major pathological changes of the extracellular Senile
Plaque (SP) and intracellular Neurofibrillary Tangles (NFTs). However, many pieces of evidence
indicate that neurogenesis disorders are also regarded as a new opinion in AD.
Objective:
This study aims to investigate the effects and regulatory mechanism of flavonoids from
the stems and leaves of Scutellaria baicalensis Georgi in promoting neurogenesis and improving
memory impairment mediated by BDNF-ERK-CREB signaling 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 rats and measure the learning and memory ability of model rats. The expression
of Ki67 protein, which is involved in cell neurogenesis, in the hippocampal gyrus of rats
was detected by the immunohistochemical method. The mRNA and protein expression levels of Grb2,
SOS1, Ras, ERK, and BDNF, in the BDNF-ERK-CREB signaling pathway, in the hippocampus
and cerebral cortex regions of rats were assayed by the Quantitative real-time PCR (qPCR) and
Western blotting methods, respectively.
Results:
Intracerebroventricular injection of composited Aβ could induce 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 rats’ memory impairment induced by
composited Aβ, lower the Ki67 protein expression in the hippocampal gyrus, and regulate the abnormal
mRNA and protein expression levels of Grb2, SOS1, Ras, ERK and BDNF in the hippocampus
and cerebral cortex regions of rat brains.
Conclusion:
Composited Aβ induced memory impairment, decreased neurogenesis and initiated
the abnormal mRNA and protein expressions of Grb2, SOS1, Ras, ERK, and BDNF in the BDNF-
ERK-CREB signaling pathway. The effects of SSF in promoting neurogenesis and improving
memory impairment may be related to the regulation of the abnormal expressions of Grb2, SOS1,
Ras, ERK, and BDNF molecules in the BDNF-ERK-CREB signaling pathway.
Funder
Hebei Provincial Natural Science Foundation
Hebei Provincial Education Department
The Key Development Subject of Pharmacology of Traditional Chinese Medicine of Chengde Medical College
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology,General Neuroscience