Neurogenesis: Unleashing the Power of Brain Renewal

In the early 20th century, the prevailing belief among scientists was that the adult brain was a static and immutable organ, with no capacity for generating new neurons. However, until the 1990s, with the advances in technology and development of novel techniques, we know that the human brain is a remarkable organ that continuously adapts and evolves throughout our lives.

The process of generating new neurons, known as neurogenesis, plays a vital role in brain plasticity, learning, memory, and overall cognitive function. In this article, we will explore the fascinating world of neurogenesis, its mechanisms, and the factors that influence it.

What is Neurogenesis?

Neurogenesis refers to the process of generation of new neurons. It occurs primarily in two regions of the brain: the subventricular zone (SVZ) and the hippocampus. The SVZ is located near the lateral ventricles. It generates neurons migrating to the olfactory bulb, which contributes to the sense of smell. In the hippocampus, the production of new neurons was found to be crucial for learning and memory (Ming & Song, 2011).

Process of Neurogenesis

Neurogenesis involves several intricate steps. It begins with the proliferation of neural stem cells, which are undifferentiated cells capable of self-renewal. These stem cells divide and give rise to progenitor cells that further differentiate into neurons, astrocytes, or oligodendrocytes (Ming & Song, 2011).

The process of neurogenesis is regulated by various molecular signals, growth factors, and environmental factors. Brain-derived neurotrophic factor (BDNF) is one of the key modulators that promotes the survival and maturation of newborn neurons. Studies found that exercise can stimulate BDNF production, and thereby enhancing neurogenesis (Miranda et al., 2019).

Neurogenesis impacts on Learning and Memory?

Neurogenesis has been suggested to have a strong link to the learning and memory processes. Studies showed that impairments in neurogenesis can lead to cognitive deficits, while enhanced neurogenesis improves cognitive performance. The birth of new neurons in the hippocampus provides a constant supply of fresh cells that integrate into existing neural circuits, contributing to the formation and retrieval of memories.

Researchers have conducted experiments using animal models showing the relationship between neurogenesis and memory. Those study showed that inhibiting neurogenesis led to a decline in the ability to form new memories (Dupret et al., 2008), while enhancing neurogenesis through environmental enrichment improved the performance of learning and memory tasks (Nilsson et al., 1999).

Stress, Aging, and Neurogenesis

Stress and aging can significantly impact neurogenesis. Chronic stress has been found to inhibit neurogenesis (Schoenfeld & Gould, 2012). Additionally, aging also affects neurogenesis. As we grow older, the rate of neurogenesis gradually decreases (Kempermann, 2015). Conversely, as mentioned previously, physical exercise can enhance neurogenesis, synaptic plasticity and learning (Nilsson et al., 1999, van Praag et al., 1999), which suggests that engaging in physical activities could be a key to maintain a good brain health.

Therapeutic Implications of Neurogenesis and the Challenges

The discovery of neurogenesis has opened up new avenues for potential therapeutic interventions. Scientists are investigating ways to harness the power of neurogenesis to treat different neuropathological conditions such as stroke, depression. Parkinson's disease and Alzheimer's disease (Rahman et al., 2021, Hanson et al., 2011, Geraerts et al., 2007, Sung et al., 2020).

The approach of targeting neurogenesis to treat neurological diseases still faces numerous challenges. Delivering therapeutic agents or interventions to stimulate neurogenesis in specific brain regions can be particularly challenging due to the need to overcome the blood-brain barrier and ensure precise targeting of desired locations. Moreover, promoting neurogenesis may carry unintended consequences. Uncontrolled or excessive neurogenesis could potentially result in abnormal neuronal growth, formation of tumors, or other detrimental effects on brain function. Additionally, while preclinical studies have shown promise for neurogenesis-based therapies in animal models, translating these findings to human patients is a complex task that requires careful consideration and understanding of the differences between species.

Take-home Messages

Neurogenesis represents a fascinating aspect of brain biology, highlighting the brain's remarkable ability to adapt and rejuvenate itself. Understanding the mechanisms and factors that influence neurogenesis provides valuable insights into how we can optimize brain health and enhance cognitive function throughout our lives. As research continues to unravel the mysteries of neurogenesis, we may unlock new therapeutic strategies to combat neurological disorders and ultimately improve the quality of life for millions of people.

References:

Dupret, D., Revest, J.-M., Koehl, M., Ichas, F., De Giorgi, F., Costet, P., Abrous, D. N., & Piazza, P. V. (2008). Spatial relational memory requires hippocampal adult neurogenesis. PloS One, 3(4), e1959. https://doi.org/10.1371/journal.pone.0001959

Geraerts, M., Krylyshkina, O., Debyser, Z., & Baekelandt, V. (2007). Concise Review: Therapeutic Strategies for Parkinson Disease Based on the Modulation of Adult Neurogenesis. Stem Cells, 25(2), 263–270. https://doi.org/10.1634/stemcells.2006-0364

Hanson, N. D., Owens, M. J., & Nemeroff, C. B. (2011). Depression, Antidepressants, and Neurogenesis: A Critical Reappraisal. Neuropsychopharmacology, 36(13), 2589–2602. https://doi.org/10.1038/npp.2011.220

Kempermann, G. (2015). Activity Dependency and Aging in the Regulation of Adult Neurogenesis. Cold Spring Harbor Perspectives in Biology, 7(11), a018929. https://doi.org/10.1101/cshperspect.a018929

Ming, G., & Song, H. (2011). Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions. Neuron, 70(4), 687–702. https://doi.org/10.1016/j.neuron.2011.05.001

Miranda, M., Morici, J. F., Zanoni, M. B., & Bekinschtein, P. (2019). Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain. Frontiers in Cellular Neuroscience, 13, 363. https://doi.org/10.3389/fncel.2019.00363

Nilsson, M., Perfilieva, E., Johansson, U., Orwar, O., & Eriksson, P. S. (1999). Enriched environment increases neurogenesis in the adult rat dentate gyrus and improves spatial memory. Journal of Neurobiology, 39(4), 569–578. https://doi.org/10.1002/(sici)1097-4695(19990615)39:4<569::aid-neu10>3.0.co;2-f

Rahman, A. A., Amruta, N., Pinteaux, E., & Bix, G. J. (2021). Neurogenesis After Stroke: A Therapeutic Perspective. Translational Stroke Research, 12(1), 1–14. https://doi.org/10.1007/s12975-020-00841-w

Schoenfeld, T., & Gould, E. (2012). Stress, Stress Hormones, and Adult Neurogenesis. Experimental Neurology, 233(1), 12–21. https://doi.org/10.1016/j.expneurol.2011.01.008

Sung, P.-S., Lin, P.-Y., Liu, C.-H., Su, H.-C., & Tsai, K.-J. (2020). Neuroinflammation and Neurogenesis in Alzheimer’s Disease and Potential Therapeutic Approaches. International Journal of Molecular Sciences, 21(3), 701. https://doi.org/10.3390/ijms21030701

van Praag, H., Christie, B. R., Sejnowski, T. J., & Gage, F. H. (1999). Running enhances neurogenesis, learning, and long-term potentiation in mice. Proceedings of the National Academy of Sciences, 96(23), 13427–13431. https://doi.org/10.1073/pnas.96.23.13427

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