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The importance of neuroplasticity and excitability of adult-born neurons in alleviating depression and anxiety-like behaviour in mice
- 1 Shrewsbury School
* Author to whom correspondence should be addressed.
Abstract
The increase in excitability of newborn adult neurons had been shown to have an antidepressant effect in rodents in previous studies, however whether the same result would apply to mature neurons remains unknown. This paper therefore proposes two experiments that investigate the role of neuroplasticity and mature neuron excitability in reducing depressive behaviour in rodents. Old neurons are known to have reduced neuroplasticity compared to newborn neurons, and the main factor influencing this seems to be the reduced NMDA:AMPA receptor ratio in mature neurons. By knocking out the NR1 gene that codes for the NMDA receptor in newborn neurons, experiment one investigates whether reduced neuroplasticity in the rodent hippocampus would induce anxiety-like behaviour, thus the importance of adult hippocampal neurogenesis (AHN) in maintaining neuroplasticity in the brain and normal affective behaviour. Subsequently the artificially made-mature neurons in the hM4Dq+ tamoxifen inducible Cre-recombinase transgenic mouse line are being activated through injection of tamoxifen followed by CNO, which increases neuronal excitability. This is hypothesised to reduce depressive behaviour to an extent however less effective than activating newborn neurons. These experiments can potentially be valuable in the application of relevant depression treatments in humans, alongside with the maintenance and stimulation of AHN with regards to its anti-depressive effect
Keywords
Neuroplasticity, Depression, Excitability, Neurogenesis
[1]. Cope, E.C. and Gould, E. (2019) ‘Adult neurogenesis, glia, and the extracellular matrix’, Cell Stem Cell, 24(5), pp. 690–705. doi:10.1016/j.stem.2019.03.023.
[2]. Snyder, J. S., Soumier, A., Brewer, M., Pickel, J., & Cameron, H. A. (2011, August). ‘Adult hippocampal neurogenesis buffers stress responses and depressive behaviour’, Nature, 476(7361), pp. 458–461. doi:10.1038/nature10287.
[3]. Cole, J. D., Espinueva, D. F., Seib, D. R., Ash, A. M., Cooke, M. B., Cahill, S. P., O’Leary, T. P., Kwan, S. S., & Snyder, J. S. (2020, June 22). ‘Adult-born hippocampal neurons undergo extended development and are morphologically distinct from neonatally-born neurons’, The Journal of Neuroscience, 40(30), pp. 5740–5756. doi:10.1523/jneurosci.1665-19.2020.
[4]. Zhao, C., Deng, W. and Gage, F.H. (2008) ‘Mechanisms and functional implications of adult neurogenesis’, Cell, 132(4), pp. 645–660. doi:10.1016/j.cell.2008.01.033.
[5]. Seri B, García-Verdugo JM, McEwen BS, and Alvarez-Buylla A (2001). Astrocytes give rise to new neurons in the adult mammalian hippocampus. J. Neurosci 21, 7153–7160. [PubMed: 11549726]
[6]. Gonçalves JT, Schafer ST, and Gage FH (2016a). Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior. Cell 167, 897–914. [PubMed: 27814520]
[7]. Cameron, H.A. and Glover, L.R. (2015) ‘Adult neurogenesis: Beyond learning and memory’, Annual Review of Psychology, 66(1), pp. 53–81. doi:10.1146/annurev-psych-010814-015006.
[8]. Tunc-Ozcan, E., Peng, C. Y., Zhu, Y., Dunlop, S., Contractor, A., & Kessler, J. A. (2019). Activating newborn neurons suppresses depression and anxiety-like behaviors’, Nature Communications, 10(1). doi:10.1038/s41467-019-11641-8.
[9]. Eisch, A.J. and Petrik, D. (2012) ‘Depression and hippocampal neurogenesis: A road to remission?’, Science, 338(6103), pp. 72–75. doi:10.1126/science.1222941.
[10]. Hansen, J. (2018, August 10). An ion channel differentiates newborn and mature neurons in the adult brain. ScienceDaily.
[11]. Mateus-Pinheiro, A., Pinto, L., Bessa, J., Morais, M., Alves, N. D., Monteiro, S., Patrício, P., Almeida, O. F. X., & Sousa, N. (2013). Sustained remission from depressive-like behavior depends on hippocampal neurogenesis. Translational Psychiatry, 3(1). doi:10.1038/tp.2012.141.
[12]. Fuchs, E. and Flügge, G. (2006) ‘Experimental animal models for the simulation of depression and anxiety’, Dialogues in Clinical Neuroscience, 8(3), pp. 323–333. doi:10.31887/dcns.2006.8.3/efuchs.
[13]. Bessa, J.M. (2009) ‘A trans-dimensional approach to the behavioral aspects of depression’, Frontiers in Behavioral Neuroscience, 3. doi:10.3389/neuro.08.001.2009.
[14]. Magnusson, K.R. (2012) ‘Aging of the NMDA receptor: From a mouse’s point of View’, Future Neurology, 7(5), pp. 627–637. doi:10.2217/fnl.12.54.
[15]. Khurana, A., Sayed, N., Singh, V., Khurana, I., Allawadhi, P., Rawat, P. S., Navik, U., Pasumarthi, S. K., Bharani, K. K., & Weiskirchen, R. (2022, September 21) ‘A comprehensive overview of CRISPR/Cas 9 technology and application thereof in Drug Discovery’, Journal of Cellular Biochemistry, 123(10), pp. 1674–1698. doi:10.1002/jcb.30329.
Cite this article
Lai,J. (2024). The importance of neuroplasticity and excitability of adult-born neurons in alleviating depression and anxiety-like behaviour in mice. Theoretical and Natural Science,46,1-8.
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The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.
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Volume title: Proceedings of the 2nd International Conference on Modern Medicine and Global Health
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