Pritam Dutta, M.Optom, FAAO

Assistant Professor, Ridley College of Optometry, Assam, India

 

Introduction

The neural system’s capacity for adaptation and resource optimisation in response to changes in physiology, trauma, novel environmental demands, and sensory experiences is known as neuroplasticity.(1)  Hebbian plasticity, which allows for the fine tuning and optimisation of synaptic connection number and strength, together with activity-dependent mechanisms that drive neuronal migration and synaptic contact creation, are the two main factors influencing cortical wiring in growing neural systems,(2) whereas, the overall balance of the network excitability is preserved by homeostatic plasticity.(3) According to recent research, this homeostatic synaptic rescaling may sustain neuroplasticity throughout an individual’s lifetime and continue to function even after the critical period has ended. It is interesting to note that the visual cortex balances the activity of a group of neurons by bringing each individual neuron’s response back to normal. This particular system plays a crucial role in effectively regulating contrast gain.(4)

Adult Neurogenesis

Figure 1 – Glimpse of different findings of adult neurogenesis

Adult neurogenesis—the creation of new neurons in adult brains—seems to be the most fascinating example of neuroplasticity in action. Of course, neurogenesis occurs in the growing central nervous system, but given that adult brains can also replace damaged neurons, and those adult brains can develop diseases like multiple sclerosis and Parkinson’s disease, this raises an intriguing topic. The findings of adult neurogenesis and its regulators are explained in ‘Figure 1’ & ‘Table 1’.

Table 1: Regulators of Adult Neurogenesis

The regulation of adult neurogenesis is a complex and finely tuned process, involving various
molecular, cellular, and environmental factors.(10) Here are some key regulators of adult
neurogenesis:
Neurotrophic Factors:

  • Neurotrophic Factor (BDNF): BDNF is a crucial neurotrophin that promotes the
    survival and differentiation of new-born neurons.
  • Insulin-like Growth Factor-1 (IGF-1): IGF-1 is involved in the regulation of cell
    proliferation and survival in the neurogenic regions.
Hormones:

  • Corticosteroids (Glucocorticoids): Stress hormones like corticosterone can have both
    positive and negative effects on neurogenesis, depending on the duration and intensity of
    exposure.
  • Sex Hormones (Oestrogen and Testosterone): These hormones influence adult
    neurogenesis, and their levels may affect the rate of neurogenesis.
Neurotransmitters:

  • Serotonin (5-HT) Serotonin plays a role in regulating the proliferation and
    differentiation of neural progenitor cells.
  • Gamma-Aminobutyric Acid (GABA):GABAergic signalling is involved in the control of
    neural progenitor cell fate.
  • Improve cognitive and non-cognitive skills
Inflammatory Signals:

  • Cytokines and Chemokines: Inflammatory signals can modulate adult neurogenesis.
    Factors associated with inflammation, both chronic and acute, can impact the rate of
    neurogenesis.
Environmental Enrichment and Physical Activity:

  • Environmental Stimuli: Exposure to an enriched environment, including increased
    cognitive and physical activity, has been shown to enhance adult neurogenesis.
  • Exercise: Physical activity promotes neurogenesis, possibly through increased blood
    flow, neurotrophic factors, and reduced inflammation.
Epigenetic Regulation:

  • DNA Methylation and Histone Modification: Epigenetic mechanisms play a role in the
    regulation of gene expression during adult neurogenesis.
Microglia:

  • Immune Cells in the Brain: Microglia, the resident immune cells in the brain, can influence adult neurogenesis through their interactions with neural progenitor cells.
Ageing and Neurodegenerative Diseases:

  • Ageing: Adult neurogenesis declines with age, and this decline is associated with cognitive decline.
  • Neurodegenerative Diseases: Conditions such as Alzheimer’s and Parkinson’s disease can impact adult neurogenesis.

The role of adult neurogenesis in function

Studies that employ virus- and transgenesis-based tactics to either selectively increase or decrease neurogenesis in the adult brain provide experimental data. All of these research have shown that hippocampus neurogenesis plays a part in fear conditioning, pattern separation, synaptic plasticity, and memory for spatial and object recognition.(11,12,13) It is thought that the contribution of new neurons to adult brain activity depends on a critical period of increased plasticity that develops about 3–6 weeks after cell division.(14) Because fewer neurons are developed in the human olfactory bulb under physiological conditions, experiments aiming at understanding the significance of neurogenesis in pathological processes have concentrated mainly on hippocampal neurogenesis.(15)

The role of neural stem/progenitor cells (NSPCs)in brain regeneration

Chemokine-directed migration towards lesions may be able to boost NSPC proliferation, but optimal neuronal differentiation within lesions and delivery routes are still complex issues that need to be resolved.(16) Other sources of non-synaptic potential neurons (NSPCs) include cells produced in vivo through controlled differentiation of NSPCs into glial cells or through cell reprogramming.(17) Furthermore, the transplantation of cells with NSPC features originating from various cellular sources, such as pluripotent cells into the lesioned brain, may contain therapeutic potential for the treatment of illnesses of the central nervous system.(18)

Conclusion

The discovery of adult neurogenesis, the generation of new neurons in the adult brain, has revolutionised our understanding of neural plasticity. Contrary to previous beliefs, ongoing neurogenic processes occur in specific brain regions, influencing learning, memory, and mood regulation. This revelation has significant implications for therapeutic interventions in neurological and psychiatric disorders, highlighting the remarkable adaptability and regenerative potential of the adult brain throughout life.

 

References

  1. Pascual-Leone, A., Amedi, A., Fregni, F., & Merabet, L. B. (2005). The plastic human brain cortex. Annual review of neuroscience28, 377–401. https://doi.org/10.1146/annurev.neuro.27.070203.144216
  2. Levelt, C. N., & Hübener, M. (2012). Critical-period plasticity in the visual cortex. Annual review of neuroscience35, 309–330. https://doi.org/10.1146/annurev-neuro-061010-113813
  3. Maffei, A., & Turrigiano, G. (2008). The age of plasticity: developmental regulation of synaptic plasticity in neocortical microcircuits. Progress in brain research169, 211–223. https://doi.org/10.1016/S0079-6123(07)00012-X-23.
  4. Carandini, M., & Heeger, D. J. (2011). Normalization as a canonical neural computation. Nature reviews. Neuroscience13(1), 51–62. https://doi.org/10.1038/nrn3136
  5. Altman J. (1962). Are new neurons formed in the brains of adult mammals?. Science (New York, N.Y.)135(3509), 1127–1128. https://doi.org/10.1126/science.135.3509.1127
  6. Kaplan, M. S., & Hinds, J. W. (1977). Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science (New York, N.Y.)197(4308), 1092–1094. https://doi.org/10.1126/science.887941
  7. Alvarez-Buylla A, Theelen M, Nottebohm F. Birth of projection neurons in the higher vocal center of the canary forebrain before, during, and after song learning. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8722-6. doi: 10.1073/pnas.85.22.8722. PMID: 3186755; PMCID: PMC282533.
  8. Gould, E., Reeves, A. J., Fallah, M., Tanapat, P., Gross, C. G., & Fuchs, E. (1999). Hippocampal neurogenesis in adult Old World primates. Proceedings of the National Academy of Sciences of the United States of America96(9), 5263–5267. https://doi.org/10.1073/pnas.96.9.5263
  9. Eriksson, P. S., Perfilieva, E., Björk-Eriksson, T., Alborn, A. M., Nordborg, C., Peterson, D. A., & Gage, F. H. (1998). Neurogenesis in the adult human hippocampus. Nature medicine4(11), 1313–1317. https://doi.org/10.1038/3305
  10. Zhao, C., Deng, W., & Gage, F. H. (2008). Mechanisms and functional implications of adult neurogenesis. Cell132(4), 645–660. https://doi.org/10.1016/j.cell.2008.01.033
  11. Jessberger, S., Clark, R. E., Broadbent, N. J., Clemenson, G. D., Jr, Consiglio, A., Lie, D. C., Squire, L. R., & Gage, F. H. (2009). Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats. Learning & memory (Cold Spring Harbor, N.Y.)16(2), 147–154. https://doi.org/10.1101/lm.1172609
  12. Saxe, M. D., Battaglia, F., Wang, J. W., Malleret, G., David, D. J., Monckton, J. E., Garcia, A. D., Sofroniew, M. V., Kandel, E. R., Santarelli, L., Hen, R., & Drew, M. R. (2006). Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proceedings of the National Academy of Sciences of the United States of America103(46), 17501–17506. https://doi.org/10.1073/pnas.0607207103
  13. Nakashiba, T., Cushman, J. D., Pelkey, K. A., Renaudineau, S., Buhl, D. L., McHugh, T. J., Rodriguez Barrera, V., Chittajallu, R., Iwamoto, K. S., McBain, C. J., Fanselow, M. S., & Tonegawa, S. (2012). Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion. Cell149(1), 188–201. https://doi.org/10.1016/j.cell.2012.01.046
  14. Marín-Burgin, A., Mongiat, L. A., Pardi, M. B., & Schinder, A. F. (2012). Unique processing during a period of high excitation/inhibition balance in adult-born neurons. Science (New York, N.Y.)335(6073), 1238–1242. https://doi.org/10.1126/science.1214956
  15. Kempermann G. (2013). Neuroscience. What the bomb said about the brain. Science (New York, N.Y.)340(6137), 1180–1181. https://doi.org/10.1126/science.1240681
  16. Li, M., Hale, J. S., Rich, J. N., Ransohoff, R. M., & Lathia, J. D. (2012). Chemokine CXCL12 in neurodegenerative diseases: an SOS signal for stem cell-based repair. Trends in neurosciences35(10), 619–628. https://doi.org/10.1016/j.tins.2012.06.003
  17. Jessberger, S., Toni, N., Clemenson, G. D., Jr, Ray, J., & Gage, F. H. (2008). Directed differentiation of hippocampal stem/progenitor cells in the adult brain. Nature neuroscience11(8), 888–893. https://doi.org/10.1038/nn.2148
  18. Yang, N., & Wernig, M. (2013). Harnessing the stem cell potential: a case for neural stem cell therapy. Nature medicine19(12), 1580–1581. https://doi.org/10.1038/nm.3425