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Immunopotentiator Thymosin Alpha-1 Promotes Neurogenesis and Cognition in the Developing Mouse via a Systemic Th1 Bias

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Abstract

In early life, the immune system plays an essential role in brain development. In our study, the immunopotentiator thymosin alpha-1 (Ta1) was peripherally administered to neonatal mice to explore whether the peripheral immunopotentiator affects neurodevelopment and cognition, and to further investigate the relevant mechanism. Compared with the control group, the Ta1 mice displayed better cognitive abilities in early life. The numbers of 5-bromodeoxyuridine (BrdU)+, nestin+, T-box transcription factor 2 (Tbr2)+, BrdU+/doublecortin (DCX)+, BrdU+/ionized calcium-binding adaptor molecule 1 (Iba1)+, and BrdU+/neuronal nuclei (NeuN)+ cells in the hippocampus were increased in the Ta1 group, accompanied by increased interleukin-4 (IL-4), interferon-gamma, brain-derived neurotrophic factor, nerve growth factor, and insulin-like growth factor-1 as well as decreased IL-6 and tumor necrosis factor-α. Furthermore, the Ta1-group showed a Th1-polarized immune response, and the neurotrophic factors were positively associated with the Th1/Th2 ratio. More importantly, administration of Ta1 blocked lipopolysaccharide-induced impairment of hippocampal neurogenesis in early life. These findings suggest that peripheral Ta1 contributes to neurogenesis and cognition probably through a systemic Th1 bias, as well as neuroprotection against LPS infection by Ta1.

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Acknowledgements

We thank Prof. Zhibin Yao for invaluable comments, as well as Qunfang Yuan for technical assistance. We also thank Prof. Libin Zhou for providing instruments. This work was supported by the Natural Science Foundation of Guangdong Province, China (2014A030310343, 2015A030313153, and 2016A030313253); the Medical Scientific Research Foundation of Guangdong Province, China (A2015382); the Doctoral Program of Guangzhou Medical University, China (2014C19).

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  1. Ge Wang, Fen He and Yunlong Xu have contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China

    Ge Wang, Yunlong Xu, Xiao Wang, Chunhua Zhou & Juntao Zou

  2. Department of Radiation Oncology, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510120, China

    Fen He

  3. South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

    Yunlong Xu

  4. Department of Anatomy, Wannan Medical College, Wuhu, 241002, China

    Yuwei Zhang

  5. Department of Neurology, The Fifth Affiliated Hospital of Southern Medical University, Guangzhou, 510900, China

    Yihong Huang

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  1. Ge Wang
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Wang, G., He, F., Xu, Y. et al. Immunopotentiator Thymosin Alpha-1 Promotes Neurogenesis and Cognition in the Developing Mouse via a Systemic Th1 Bias. Neurosci. Bull. 33, 675–684 (2017). https://doi.org/10.1007/s12264-017-0162-x

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