Effects of Zibu Piyin recipe on SNK-SPAR pathway in neuron injury induced by glutamate.
OBJECTIVE
To 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.


METHODS
The 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.


RESULTS
ZBPYR 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).


CONCLUSIONS
The 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.
Zhan
Li-bin
LB
The Second Affiliated Hospital, Dalian Medical University, Dalian, China. zlbdl_04@vip.163.com
Sui
Hua
H
Lu
Xiao-guang
XG
Sun
Chang-kai
CK
Zhang
Jian
J
Ma
Hui
H
D000818:Animals; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044967:Serum
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D004365:Drugs, Chinese Herbal; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C479629:Sipa1l1 protein, rat; C531140:zibu piyin; D018698:Glutamic Acid; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C444640:serum-inducible kinase