Role of BDNF Expression Through Microglial Polarization in Adult Hippocampal Neurogenesis in Depression and the Therapeutics

Research Article
Open access

Role of BDNF Expression Through Microglial Polarization in Adult Hippocampal Neurogenesis in Depression and the Therapeutics

Sheng Gao 1*
  • 1 Shanghai New Epoch Bilingual School, Shanghai, 200003, China    
  • *corresponding author Crowded_of_stars@163.com
Published on 20 June 2025 | https://doi.org/10.54254/2753-8818/2025.24204
TNS Vol.116
ISSN (Print): 2753-8826
ISSN (Online): 2753-8818
ISBN (Print): 978-1-80590-197-6
ISBN (Online): 978-1-80590-198-3

Abstract

The present study tests the proposition that enhancement of BDNF by polarizing microglial cells from M1 to M2 contribute to the phenomenon of hippocampal neurogenesis and synaptic plasticity, thus reducing depressive-like behaviors. The experimental design covers both in vitro and in vivo, with BACE1-modified microglial culture, co-culture with neural progenitors, and a mouse model of depressed state. Thus, the present study intends to understand exactly how microglial polarization is connected to the alteration in BDNF and adult hippocampal neurogenesis in depression. It is possible that the results obtained will shed light on the new therapeutic approaches to influencing microglial polarization and BDNF receptor expression in depressive disorders and improving the efficacy of the therapies. The present study adds to the current knowledge about the neuroinflammation process in psychiatric diseases, as well as possibly offering hope for better biology-driven treatment options for depression in the future.

Keywords:

depression, microglial polarization, BDNF expression, neurogenesis, BACE1 inhibition

Gao,S. (2025). Role of BDNF Expression Through Microglial Polarization in Adult Hippocampal Neurogenesis in Depression and the Therapeutics. Theoretical and Natural Science,116,18-26.
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References

[1]. Hu, X., Leak, R., Shi, Y., et al. (2015). Microglial and macrophage polarization—new prospects for brain repair. Nature Reviews Neurology, 11, 56-64. https://doi.org/10.1038/nrneurol.2014.207

[2]. Harley, S. B. R., Willis, E. F., Shaikh, S. N., et al. (2021). Selective Ablation of BDNF from Microglia Reveals Novel Roles in Self-Renewal and Hippocampal Neurogenesis. The Journal of Neuroscience, 41(19), 4172. https://doi.org/10.1523/JNEUROSCI.2539-20.2021

[3]. Han, M., Zeng, D., Tan, W., et al. (2025). Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior. Neural Regeneration Research, 20(1), 159-173. https://doi.org/10.4103/NRR.NRR-D-23-01419

[4]. Wen, Y., Xu, J., Shen, J., et al. (2024). Esketamine Prevents Postoperative Emotional and Cognitive Dysfunction by Suppressing Microglial M1 Polarization and Regulating the BDNF-TrkB Pathway in Ageing Rats with Preoperative Sleep Disturbance. Molecular Neurobiology, 61(8), 5680-5698. https://doi.org/10.1007/s12035-023-03860-4

[5]. Fang, S., Wu, Z., Guo, Y., et al. (2023). Roles of microglia in adult hippocampal neurogenesis in depression and their therapeutics. Frontiers in Immunology, 14, 1193053. https://doi.org/10.3389/fimmu.2023.1193053

[6]. Hampel, H., Vassar, R., De Strooper, B., et al. (2020). The β-Secretase BACE1 in Alzheimer's disease. Biological Psychiatry, 89(8), 745-756. https://doi.org/10.1016/j.biopsych.2020.02.001

[7]. Orihuela, R., McPherson, C. A., & Harry, G. J. (2015). Microglial M1/M2 polarization and metabolic states. British Journal of Pharmacology, 173(4), 649-665. https://doi.org/10.1111/bph.13139

[8]. Liu, J., Hjorth, E., Zhu, M., et al. (2013). Interplay between human microglia and neural stem/progenitor cells in an allogeneic co-culture model. Journal of Cellular and Molecular Medicine, 17(11), 1434-1443. https://doi.org/10.1111/jcmm.12123

[9]. Saaltink, D., Van Zwet, E. W., & Vreugdenhil, E. (2020). Doublecortin-Like Is Implicated in Adult Hippocampal Neurogenesis and in Motivational Aspects to Escape from an Aversive Environment in Male Mice. eNeuro, 7(5), ENEURO.0324-19.2020. https://doi.org/10.1523/eneuro.0324-19.2020

[10]. Albert, J.S. (2009). Progress in the development of beta-secretase inhibitors for Alzheimer's disease. Progress in Medicinal Chemistry, 48, 133-61. doi: 10.1016/s0079-6468(09)04804-8

[11]. Albert, J.S. (2009). Progress in the development of beta-secretase inhibitors for Alzheimer's disease. Progress in Medicinal Chemistry, 48, 133-61. doi: 10.1016/s0079-6468(09)04804-8

[12]. Singh, N., Das, B., Zhou, J., et al. (2022). Targeted BACE-1 inhibition in microglia enhances amyloid clearance and improved cognitive performance. Science Advances, 8(29), eabo3610. doi: 10.1126/sciadv.abo3610

[13]. Sun, J., & Roy, S. (2018). The physical approximation of APP and BACE-1: A key event in alzheimer's disease pathogenesis. Developmental Neurobiology, 78(3), 340-347. doi: 10.1002/dneu.22556

[14]. Liu, L., Tang, J., Liang, X., et al. (2024). Running exercise alleviates hippocampal neuroinflammation and shifts the balance of microglial M1/M2 polarization through adiponectin/AdipoR1 pathway activation in mice exposed to chronic unpredictable stress. Molecular Psychiatry, 29, 2031-2042. https://doi.org/10.1038/s41380-024-02464-1

[15]. Albert, J.S. (2009). Progress in the development of beta-secretase inhibitors for Alzheimer's disease. Progress in Medicinal Chemistry, 48, 133-61. doi: 10.1016/s0079-6468(09)04804-8

Cite this article

Gao,S. (2025). Role of BDNF Expression Through Microglial Polarization in Adult Hippocampal Neurogenesis in Depression and the Therapeutics. Theoretical and Natural Science,116,18-26.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

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About volume

Volume title: Proceedings of the 3rd International Conference on Modern Medicine and Global Health

ISBN：978-1-80590-197-6(Print) / 978-1-80590-198-3(Online)
Editor：Sheiladevi Sukumaran
Conference website: https://2025.icmmgh.org/
Conference date: 20 January 2025
Series: Theoretical and Natural Science
Volume number: Vol.116
ISSN：2753-8818(Print) / 2753-8826(Online)

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References

[1]. Hu, X., Leak, R., Shi, Y., et al. (2015). Microglial and macrophage polarization—new prospects for brain repair. Nature Reviews Neurology, 11, 56-64. https://doi.org/10.1038/nrneurol.2014.207

[2]. Harley, S. B. R., Willis, E. F., Shaikh, S. N., et al. (2021). Selective Ablation of BDNF from Microglia Reveals Novel Roles in Self-Renewal and Hippocampal Neurogenesis. The Journal of Neuroscience, 41(19), 4172. https://doi.org/10.1523/JNEUROSCI.2539-20.2021

[3]. Han, M., Zeng, D., Tan, W., et al. (2025). Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior. Neural Regeneration Research, 20(1), 159-173. https://doi.org/10.4103/NRR.NRR-D-23-01419

[4]. Wen, Y., Xu, J., Shen, J., et al. (2024). Esketamine Prevents Postoperative Emotional and Cognitive Dysfunction by Suppressing Microglial M1 Polarization and Regulating the BDNF-TrkB Pathway in Ageing Rats with Preoperative Sleep Disturbance. Molecular Neurobiology, 61(8), 5680-5698. https://doi.org/10.1007/s12035-023-03860-4

[5]. Fang, S., Wu, Z., Guo, Y., et al. (2023). Roles of microglia in adult hippocampal neurogenesis in depression and their therapeutics. Frontiers in Immunology, 14, 1193053. https://doi.org/10.3389/fimmu.2023.1193053

[6]. Hampel, H., Vassar, R., De Strooper, B., et al. (2020). The β-Secretase BACE1 in Alzheimer's disease. Biological Psychiatry, 89(8), 745-756. https://doi.org/10.1016/j.biopsych.2020.02.001

[7]. Orihuela, R., McPherson, C. A., & Harry, G. J. (2015). Microglial M1/M2 polarization and metabolic states. British Journal of Pharmacology, 173(4), 649-665. https://doi.org/10.1111/bph.13139

[8]. Liu, J., Hjorth, E., Zhu, M., et al. (2013). Interplay between human microglia and neural stem/progenitor cells in an allogeneic co-culture model. Journal of Cellular and Molecular Medicine, 17(11), 1434-1443. https://doi.org/10.1111/jcmm.12123

[9]. Saaltink, D., Van Zwet, E. W., & Vreugdenhil, E. (2020). Doublecortin-Like Is Implicated in Adult Hippocampal Neurogenesis and in Motivational Aspects to Escape from an Aversive Environment in Male Mice. eNeuro, 7(5), ENEURO.0324-19.2020. https://doi.org/10.1523/eneuro.0324-19.2020

[10]. Albert, J.S. (2009). Progress in the development of beta-secretase inhibitors for Alzheimer's disease. Progress in Medicinal Chemistry, 48, 133-61. doi: 10.1016/s0079-6468(09)04804-8

[11]. Albert, J.S. (2009). Progress in the development of beta-secretase inhibitors for Alzheimer's disease. Progress in Medicinal Chemistry, 48, 133-61. doi: 10.1016/s0079-6468(09)04804-8

[12]. Singh, N., Das, B., Zhou, J., et al. (2022). Targeted BACE-1 inhibition in microglia enhances amyloid clearance and improved cognitive performance. Science Advances, 8(29), eabo3610. doi: 10.1126/sciadv.abo3610

[13]. Sun, J., & Roy, S. (2018). The physical approximation of APP and BACE-1: A key event in alzheimer's disease pathogenesis. Developmental Neurobiology, 78(3), 340-347. doi: 10.1002/dneu.22556

[14]. Liu, L., Tang, J., Liang, X., et al. (2024). Running exercise alleviates hippocampal neuroinflammation and shifts the balance of microglial M1/M2 polarization through adiponectin/AdipoR1 pathway activation in mice exposed to chronic unpredictable stress. Molecular Psychiatry, 29, 2031-2042. https://doi.org/10.1038/s41380-024-02464-1

[15]. Albert, J.S. (2009). Progress in the development of beta-secretase inhibitors for Alzheimer's disease. Progress in Medicinal Chemistry, 48, 133-61. doi: 10.1016/s0079-6468(09)04804-8

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