- Author:
Li-bin ZHAN
1
;
Hua SUI
;
Xiao-guang LU
;
Chang-kai SUN
;
Jian ZHANG
;
Hui MA
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cells, Cultured; Disks Large Homolog 4 Protein; Drugs, Chinese Herbal; pharmacology; GTPase-Activating Proteins; genetics; metabolism; Gene Expression Regulation; drug effects; Glutamic Acid; toxicity; Hippocampus; drug effects; enzymology; pathology; Intracellular Signaling Peptides and Proteins; genetics; metabolism; Membrane Proteins; genetics; metabolism; Neurons; drug effects; enzymology; pathology; Protein Kinases; genetics; metabolism; Protein-Serine-Threonine Kinases; RNA, Messenger; genetics; metabolism; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; genetics; metabolism; Reverse Transcriptase Polymerase Chain Reaction; Serum
- From: Chinese journal of integrative medicine 2008;14(2):117-122
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo investigate the relationship between the excitotoxicity and serum-inducible kinase (SNK) and spine-associated Rap GTPase-activating protein (SPAR) pathway in primary hippocampal neuron injury induced by glutamate and furthermore, to explore the molecular mechanism of neuroprotection of Zibu Piyin Recipe (ZBPYR) and the relationship between ZBPYR and the morphological regulation of dendritic spines.
METHODSThe serum containing ZBPYR was prepared by seropharmacology. Reverse transcription and polymerase chain reaction (RT-PCR) was used to detect the expression of mRNA for SNK, SPAR, postsynaptic density protein 95 (PSD-95) and N-methyl-D-aspartate (NMDA) receptor subunits (NR1, NR2A and NR2B) in primary rat hippocampal neuron cultures after pretreatment with 10 micromol/L glutamate and ZBPYR serum.
RESULTSZBPYR serum pretreatment resulted in a significant down-regulation of glutamate-induced SNK mRNA expression (P<0.05). Significant up-regulation was seen on the mRNA expression of SPAR and PSD-95 (P<0.05). All these changes were dose-dependent. The mRNA expression of NR1, NR2A and NR2B was down-regulated to different degrees (P<0.05).
CONCLUSIONThe mechanism of effect of ZBPYR on glutamate-induced excitotoxicity may be related to the regulation of SNK-SPAR signal pathway. ZBPYR may play a role in protecting and maintaining the normal morphology and structure of dendritic spines, which may be achieved by inhibiting the excessive activation of NMDA receptors.