The Mechanism of Activating SuM Modified ABN to Improve Memory and Emotional Function in AD

Research Article
Open access

The Mechanism of Activating SuM Modified ABN to Improve Memory and Emotional Function in AD

Xiaoyan Liu 1*
  • 1 Life Science, Tongji University, Shanghai 200000, China    
  • *corresponding author 2250294@tongji.edu.cn
Published on 13 June 2025 | https://doi.org/10.54254/2753-8818/2025.24038
TNS Vol.115
ISSN (Print): 2753-8826
ISSN (Online): 2753-8818
ISBN (Print): 978-1-80590-193-8
ISBN (Online): 978-1-80590-194-5

Abstract

Alzheimer's disease (AD) patients experience declining memory, anxiety, and depression along with a decrease in adult hippocampal neurogenesis (AHN). It's still unclear if improving AHN in the damaged AD brain will improve affective and cognitive performance. According to earlier studies, in two different AD mice models, 5×FAD and 3×Tg-AD, patterned optogenetic activation of the hypothalamic supramammillary nucleus (SuM) increases AHN. Interestingly, these AD mice's memory and emotional deficiencies are restored when SuM-enhanced adult-born neurons (ABNs) are chemogenetic activated. In contrast, behavioral impairments cannot be restored by SuM stimulation alone or by activating ABNs without modifying SuM. This paper will design 3 experiments to explore the mechanism of activating SuM modified ABN to improve memory and emotional function in AD, including who enhances cognitive and emotional function, the activition of microglia and the long-term effect of SuM modified ABNs on memory and emotion function of AD mice.

Keywords:

adult hippocampal neurogenesis, supramammillary nucleus, Alzheimers’s disease, microglia, adult-born neurons

Liu,X. (2025). The Mechanism of Activating SuM Modified ABN to Improve Memory and Emotional Function in AD. Theoretical and Natural Science,115,1-9.
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References

[1]. Li, Y.D., Luo, Y.J., Song, J. (2023). Activation of hypothalamic-enhanced adult-born neurons restores cognitive and affective function in Alzheimer’s disease. Cell Stem Cell, 30, 415–432.

[2]. Li, Y.D., Luo, Y.J., Song, J. (2022). Hypothalamic modulation of adult hippocampal neurogenesis in mice confers activity-dependent regulation of memory and anxiety-like behavior. Nature neuroscience,25,630-645.

[3]. Moreno-Jime´nez, E.P., Flor-Garcı´a, M., Terreros-Roncal, J., Ra´bano, A., Cafini, F., Pallas-Bazarra, N., A ´vila, J., and Llorens-Martı´n, M. (2019). Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nat. Med. 25, 554–560.

[4]. Tobin, M.K., Musaraca, K., Disouky, A., Shetti, A., Bheri, A., Honer, W.G., Kim, N., Dawe, R.J., Bennett, D.A., Arfanakis, K., and Lazarov, O. (2019). Human hippocampal neurogenesis persists in aged adults and Alzheimer’s disease patients. Cell Stem Cell 24, 974–982.e3.

[5]. Zhang, X., Wei, X., Mei, Y., Wang, D., Wang, J., Zhang, Y., Li, X., Gu, Y., Peng, G., and Sun, B. (2021). Modulating adult neurogenesis affects syn aptic plasticity and cognitive functions in mouse models of Alzheimer’s disease. Stem Cell Rep. 16, 3005–3019.

[6]. Wang, W.B., Li, Y.Z., Ma, F.L., Zhong, L., et al. (2023). Microglial repopulation reverses cognitive and synaptic deficits in an Alzheimer’s disease model by restoring BDNF signaling. Brain, Behavior, and Immunity, 113, 275-288.

[7]. Zhu, H., Aryal, D.K., Olsen, R.H., Urban, D.J., Swearingen, A., Forbes, S., Roth, B.L., and Hochgeschwender, U. (2016). Cre-dependent DREADD (Designer Receptors Exclusively Activated by Designer Drugs) mice. Genesis 54, 439–446.

[8]. Sarlus, H., and Heneka, M.T. (2017). Microglia in Alzheimer’s disease. J. Clin. Invest. 127, 3240–3249.

[9]. Franco-Bocanegra, D.K., McAuley, C., Nicoll, J.A.R., and Boche, D. (2019). Molecular mechanisms of microglial motility: changes in ageing and Alzheimer’s disease. Cells 8, 639.

[10]. Gonza´lez Ibanez, F., Picard, K., Bordeleau, M., Sharma, K., Bisht, K., and Tremblay, M.E `. (2019). Immunofluorescence staining using IBA1 and TMEM119 for microglial density, morphology, and peripheral myeloid cell infiltration analysis in mouse brain. J. Vis. Exp.

[11]. Leng F, Edison P. (2021). Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol, 17(3), 157-172.

[12]. Hu, J., Chen, Q., Zhu, H.R. (2023). Microglial Piezo1 senses Aβ fibril stiffness to restrict Alzheimer's disease. Neuron, 111(1), 15- 29.

[13]. Tong, L., Han, S.S., Xue, Y. (2023). Single cell in vivo optogenetic stimulation by two-photon excitation fluorescence transfer. iScience,107857.


Cite this article

Liu,X. (2025). The Mechanism of Activating SuM Modified ABN to Improve Memory and Emotional Function in AD. Theoretical and Natural Science,115,1-9.

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:978-1-80590-193-8(Print) / 978-1-80590-194-5(Online)
Editor:Sheiladevi Sukumaran
Conference website: https://2025.icmmgh.org/
Conference date: 20 January 2025
Series: Theoretical and Natural Science
Volume number: Vol.115
ISSN:2753-8818(Print) / 2753-8826(Online)

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References

[1]. Li, Y.D., Luo, Y.J., Song, J. (2023). Activation of hypothalamic-enhanced adult-born neurons restores cognitive and affective function in Alzheimer’s disease. Cell Stem Cell, 30, 415–432.

[2]. Li, Y.D., Luo, Y.J., Song, J. (2022). Hypothalamic modulation of adult hippocampal neurogenesis in mice confers activity-dependent regulation of memory and anxiety-like behavior. Nature neuroscience,25,630-645.

[3]. Moreno-Jime´nez, E.P., Flor-Garcı´a, M., Terreros-Roncal, J., Ra´bano, A., Cafini, F., Pallas-Bazarra, N., A ´vila, J., and Llorens-Martı´n, M. (2019). Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nat. Med. 25, 554–560.

[4]. Tobin, M.K., Musaraca, K., Disouky, A., Shetti, A., Bheri, A., Honer, W.G., Kim, N., Dawe, R.J., Bennett, D.A., Arfanakis, K., and Lazarov, O. (2019). Human hippocampal neurogenesis persists in aged adults and Alzheimer’s disease patients. Cell Stem Cell 24, 974–982.e3.

[5]. Zhang, X., Wei, X., Mei, Y., Wang, D., Wang, J., Zhang, Y., Li, X., Gu, Y., Peng, G., and Sun, B. (2021). Modulating adult neurogenesis affects syn aptic plasticity and cognitive functions in mouse models of Alzheimer’s disease. Stem Cell Rep. 16, 3005–3019.

[6]. Wang, W.B., Li, Y.Z., Ma, F.L., Zhong, L., et al. (2023). Microglial repopulation reverses cognitive and synaptic deficits in an Alzheimer’s disease model by restoring BDNF signaling. Brain, Behavior, and Immunity, 113, 275-288.

[7]. Zhu, H., Aryal, D.K., Olsen, R.H., Urban, D.J., Swearingen, A., Forbes, S., Roth, B.L., and Hochgeschwender, U. (2016). Cre-dependent DREADD (Designer Receptors Exclusively Activated by Designer Drugs) mice. Genesis 54, 439–446.

[8]. Sarlus, H., and Heneka, M.T. (2017). Microglia in Alzheimer’s disease. J. Clin. Invest. 127, 3240–3249.

[9]. Franco-Bocanegra, D.K., McAuley, C., Nicoll, J.A.R., and Boche, D. (2019). Molecular mechanisms of microglial motility: changes in ageing and Alzheimer’s disease. Cells 8, 639.

[10]. Gonza´lez Ibanez, F., Picard, K., Bordeleau, M., Sharma, K., Bisht, K., and Tremblay, M.E `. (2019). Immunofluorescence staining using IBA1 and TMEM119 for microglial density, morphology, and peripheral myeloid cell infiltration analysis in mouse brain. J. Vis. Exp.

[11]. Leng F, Edison P. (2021). Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol, 17(3), 157-172.

[12]. Hu, J., Chen, Q., Zhu, H.R. (2023). Microglial Piezo1 senses Aβ fibril stiffness to restrict Alzheimer's disease. Neuron, 111(1), 15- 29.

[13]. Tong, L., Han, S.S., Xue, Y. (2023). Single cell in vivo optogenetic stimulation by two-photon excitation fluorescence transfer. iScience,107857.