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Neuroprotective Effect by Wutoutang in Spinal Nerve Ligation Mice via BDNF/TrkB Signaling Pathway / 中国实验方剂学杂志
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 23-30, 2020.
Article in Chinese | WPRIM | ID: wpr-862656
ABSTRACT

Objective:

To investigate the neuroprotective effect and mechanism by Wutoutang (WTT) in the spinal nerve ligation (SNL) mice by neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling BDNF/tyrosine kinase receptor B (TrkB).

Method:

The 40 mice were randomly divided into Sham group, SNL group, WTT group(126 mg·kg-1), ANA-12+ WTT group.The L5 spinal nerve ligation model mice were established in mice, After that, WTT was administrated from the first day to the 10th day, then the consecutive 7-day hippocampal injection of ANA-12(0.05 nmol·L-1)were lasted for 7 days.The levels of brain-derived BDNF, cAMP-response element binding protein(CREB), and protein kinase B(Akt)and the change of hippocampal glutamatergic and GABAergic neurons in mice were detected by tissue immunofluorescence.E14 pregnant ICR mice were sacrificed and the hippocampus were dissected which were divided into control group, glycine group, tumo necrosis factor(TNF)-α(5 mg·L-1)+ glycine group, TNF-α+ WTT(5 mg·L-1)+ glycine group, TNF-α+ WTT+ glycine+ BDNF-siRNA group, TNF-α+ WTT+ glycine+ Akt-siRNA group, TNF-α+ WTT+ glycine+ CREB-siRNA group, the primary and secondary dendrrictes, in which the arrowheads indicate the expression od postsynapti desity protein 95(PSD95) in the shafts and arrows were tested by cellular immunofluorescence.The neurons were divided into control group, glycine group, ANA-12 group(0.5 mmol·L-1), ANA-12+ glycine group, ANA-12+ WTT group, ANA-12+ WTT+ glycine group, the morphology of hippocampal neurons were tested by cellular immunofluorescence.

Result:

Compared with Sham group, BDNF, Akt and CREB positive cell of SNL group decreased significantly(P<0.01), the hippocampal glutamatergic and GABAergic neurons out of balance(P<0.01). Compared with SNL group, the BDNF, Akt and CREB positive cell of WTT group increased significantly(P<0.01), Glutamine-aminobutyric acid neurons regein balance(P<0.01). Compared with WTT group, BDNF and CREB positive cell of ANA-12+ WTT group decreased significantly(P<0.05), Glutamine-aminobutyric acid neurons was disorderedd(P<0.05). Comparaed with control group, the level of PSD95 of glycine group were increase significantly(P<0.01). The number of dendritic spine density apically and basally of glycine group were increase significantly(P<0.01), but the primary and secondary dendrites of ANA-12 group, ANA-12+ glycine group, ANA-12+ WTT group, ANA-12+ WTT+ glycine group were not change.Comparaed with glycine group, the level of PSD95 of TNF-α+ glycine group were decreased significantly(P<0.01). Comparaed with TNF-α+ glycine group, the level of PSD95 of TNF-α+ WTT+ glycine group were increase significantly(P<0.01). Comparaed with TNF-α+ WTT+ glycine group, the level of PSD95 of TNF-α+ WTT+ glycine+ BDNF-siRNA group, TNF-α+ WTT+ glycine+ Akt-siRNA group, TNF-α+ WTT+ glycine+ CREB-siRNA group were decreased significantly(P<0.01).

Conclusion:

In vivo and in vitro studies have shown that the WTT mediated remission of the primary hippocampal glutamatergic neurons were dependent on the BDNF/TrkB pathway.

Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2020 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2020 Type: Article