Catalpol Enhances Neurogenesis And Inhibits Apoptosis Of New Neurons Via BDNF, But Not The BDNF/Trkb Pathway

Abstract

Background

The role of catalpol in brain neurogenesis and newborn neuron survival has not been previously determined in permanent middle cerebral artery occlusion (pMCAO).

Methods

Fifty-four rats were divided into 6 groups: pMCAO (model, n=9); sham operation (NS, n=9); catalpol treatment (5 mg/kg and 10 mg/kg subgroups, n=9 each); K252a (n=9); and K252a+catalpol 5 mg/kg (n=9) with stroke. The effects of catalpol on behavior, neurogenesis surrounding the infarction ipsilateral to pMCAO, and the expression of brain-derived neurotrophic factor (BDNF) and its receptor (TrkB) were evaluated. Vehicle or, K252a (i.p.), an inhibitor of TrkB phosphorylase.

Results

Repeated administration of catalpol reduced neurological deficits and significantly improved neurogenesis. Catalpol increased the number of newborn immature neurons, as determined by BrdU⁺-Nestin⁺ and BrdU⁺-Tuj-1⁺ staining, and downregulated cleaved caspase 3 in Tuj-1⁺ cells at day 7 following stroke. Moreover, catalpol increased the protein expression of Tuj-1, MAP2, and the Bcl-2/Bax ratio, as determined using Western blot. Catalpol also significantly increased brain levels of BDNF, but not TrkB, resulting in enhanced survival of newborn neurons via inhibition of apoptosis.

Conclusion

Catalpol may contribute to neurogenesis in infarcted brain regions and help promote the survival of newborn neurons by activating BDNF, but not BDNF/TrkB signaling.

Keywords:

• catalpol
• neurogenesis
• permanent middle cerebral artery occlusion
• pMCAO
• brain derived neurotrophic factor
• BDNF
• neurological function

Acknowledgment

The authors gratefully acknowledge Allan V. Kalueff, Ph.D. for his review and helpful comments regarding this paper.

Abbreviations

pMCAO, permanent middle cerebral artery occlusion; BDNF, brain-derived neurotrophic factor; EPO, erythropoietin; VEGF, vascular endothelial growth factor.

Ethics Approval And Informed Consent

All experiments were performed in accordance with the Basel Declaration and China’s Guidelines for Care and Use of Laboratory Animals. The experimental protocol was approved by the Experimental Animal Ethics Committee of College of Pharmaceutical Sciences & Chinese Medicine, Southwest University.

Data Availability

The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.

Author Contributions

All authors were involved in the design. Yali Shao, Lei Qin, and Jing-Huan Wang performed the study. Jing-Huan Wang, Yali Shao, Lei Qin, and Shan Feng performed acquisition, processing, analysis, and interpretation of data, and helped to revise the paper. Hui-Feng Zhu, Dong Wan, Jing-Huan Wang, and Yun-Bin Jiang wrote the manuscript. Hui-Feng Zhu and Dong Wan were principal investigators and corresponding authors. All authors gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China (81873034), the Fundamental Research Funds for the Central Universities (XDJK2012B010), and the Natural Science Foundation Project of CQ CSTC (cstc2014jcyjA10083; 2018jcyjAX0158).