Abstract

Review Article

Adult Neurogenesis: A Review of Current Perspectives and Implications for Neuroscience Research

Alex, Gideon S*, Olanrewaju Oluwaseun Oke, Joy Wilberforce Ekokojde, Tolulope Judah Gbayisomore, Martina C. Anene-Ogbe, Farounbi Glory and Joshua Ayodele Yusuf

Published: 12 November, 2024 | Volume 8 - Issue 2 | Pages: 106-114

Background: The study of new neuron formation in the adult brain has sparked controversy and ignited interest among scientists in recent times, these include its occurrence and location in the adult human brain, functional significance, variation in study methods, translation from animal model to human, and ethical challenges involving neural stem cell research. 
Aim: To provide a comprehensive understanding of adult neurogenesis, functional significance, and challenges and explore the latest advances in the study of adult neurogenesis. 
Methodology: An extensive and systematic search of electronic databases (Medline, Scopus, Web of Science) was conducted using keywords related to adult neurogenesis and techniques involved in its study. 
Results: The mechanism of adult neurogenesis was found to occur in specific brain regions such as the subgranular zone of the dentate gyrus and subventricular zone of the lateral ventricle. Adult neurogenesis is vital neural plasticity, providing a potential mechanism for the brain to adapt and reorganize in response to environmental cues and experiences. Cutting-edge research and sophisticated imaging techniques, such as two-photon microscopy, MRI, optogenetic, and stem-cell-based therapies have provided deeper insight into the study of adult neurogenesis. 
Conclusion: The study of neurogenesis is important for understanding nervous system development, physiology, pathology, and exploring neuroplasticity. Its advancement is challenged by some ethical concerns regarding embryonic, pluripotent stem cells, and the need for safe, and noninvasive study methods. Although recent breakthroughs in neuroimaging, microscopic techniques, and genetic tools are aiding real-time study of adult neurogenesis.

Read Full Article HTML DOI: 10.29328/journal.jnnd.1001102 Cite this Article Read Full Article PDF

Keywords:

Adult neurogenesis; Neural stem cell; Neuroplasticity; Emerging technologies

References

  1. Moreno-Jiménez EP, Terreros-Roncal J, Flor-García M, Rábano A, Llorens-Martín M. Evidences for adult hippocampal neurogenesis in humans. J Neurosci. 2021;41(12):2541-2553. Available from: https://doi.org/10.1523/jneurosci.0675-20.2020
  2. Denoth-Lippuner A, Jessberger S. Formation and integration of new neurons in the adult hippocampus. Nat Rev Neurosci. 2021;22(4):223-236. Available from: https://doi.org/10.1038/s41583-021-00433-z
  3. Lieberwirth C, Pan Y, Liu Y, Zhang Z, Wang Z. Hippocampal adult neurogenesis: Its regulation and potential role in spatial learning and memory. Brain Res. 2016;1644:127-140. Available from: https://doi.org/10.1016/j.brainres.2016.05.015
  4. Eriksson PS, Perfilieva E, Björk-Eriksson T, Alborn AM, Nordborg C, Peterson DA, et al. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4(11):1313-1317. Available from: https://doi.org/10.1038/3305
  5. Horgusluoglu E, Nudelman K, Nho K, Saykin AJ. Adult neurogenesis and neurodegenerative diseases: a systems biology perspective. Am J Med Genet B Neuropsychiatr Genet. 2017;174(1):93-112. Available from: https://doi.org/10.1002/ajmg.b.32429
  6. Kuhn HG, Toda T, Gage FH. Adult hippocampal neurogenesis: a coming-of-age story. J Neurosci. 2018;38(49):10401-10410. Available from: https://doi.org/10.1523/jneurosci.2144-18.2018
  7. Kempermann G. Adult neurogenesis: an evolutionary perspective. Cold Spring Harb Perspect Biol. 2016;8(2). Available from: https://doi.org/10.1101/cshperspect.a018986
  8. Kokoeva MV, Yin H, Flier JS. Neurogenesis in the hypothalamus of adult mice: potential role in energy balance. Science. 2005;310(5748):679-683. Available from: https://doi.org/10.1126/science.1115360
  9. Egeland M, Zunszain PA, Pariante CM. Molecular mechanisms in the regulation of adult neurogenesis during stress. Nat Rev Neurosci. 2015;16(4):189-200. Available from: https://doi.org/10.1038/nrn3855
  10. Choe Y, Pleasure SJ, Mira H. Control of adult neurogenesis by short-range morphogenic-signaling molecules. Cold Spring Harb Perspect Biol. 2016;8(3):a018887. Available from: https://doi.org/10.1101/cshperspect.a018887
  11. Bowman AN, Van Amerongen R, Palmer TD, Nusse R. Lineage tracing with Axin2 reveals distinct developmental and adult populations of Wnt/β-catenin–responsive neural stem cells. Proc Natl Acad Sci U S A. 2013;110(18):7324-7329. Available from: https://doi.org/10.1073/pnas.1305411110
  12. Hirabayashi Y, Itoh Y, Tabata H, Nakajima K, Akiyama T, Masuyama N, Gotoh Y. The Wnt/β-catenin pathway directs neuronal differentiation of cortical neural precursor cells. Development. 2004;131(12):2791-801. Available from: https://doi.org/10.1242/dev.01165
  13. Munji RN, Choe Y, Li G, Siegenthaler JA, Pleasure SJ. Wnt signaling regulates neuronal differentiation of cortical intermediate progenitors. J Neurosci. 2011;31(5):1676-1687. Available from: https://doi.org/10.1523/jneurosci.5404-10.2011
  14. Chen J, Park CS, Tang SJ. Activity-dependent synaptic Wnt release regulates hippocampal long-term potentiation. J Biol Chem. 2006;281(17):11910-11916. Available from: https://doi.org/10.1074/jbc.m511920200
  15. Machon O, Backman M, Machonova O, Kozmik Z, Vacik T, Andersen L, et al. A dynamic gradient of Wnt signaling controls initiation of neurogenesis in the mammalian cortex and cellular specification in the hippocampus. Dev Biol. 2007;311(1):223-237. Available from: https://doi.org/10.1016/j.ydbio.2007.08.038
  16. Wrobel CN, Mutch CA, Swaminathan S, Taketo MM, Chenn A. Persistent expression of stabilized β-catenin delays maturation of radial glial cells into intermediate progenitors. Dev Biol. 2007;309(2):285-297. Available from: https://doi.org/10.1016/j.ydbio.2007.07.013
  17. Panchision DM, McKay RD. The control of neural stem cells by morphogenic signals. Curr Opin Genet Dev. 2002;12(4):478-487. Available from: https://doi.org/10.1016/s0959-437x(02)00329-5
  18. Ng JM, Curran T. The Hedgehog's tale: developing strategies for targeting cancer. Nat Rev Cancer. 2011;11(7):493-501. Available from: https://doi.org/10.1038/nrc3079
  19. Li G, Hidalgo A. Adult neurogenesis in the Drosophila brain: the evidence and the void. Int J Mol Sci. 2020;21(18):6653. Available from: https://doi.org/10.3390/ijms21186653
  20. Fernández-Hernández I, Rhiner C, Moreno E. Adult neurogenesis in Drosophila. Cell Rep. 2013;3(6):1857-1865. Available from: https://doi.org/10.1016/j.celrep.2013.05.034
  21. Ito K, Hotta Y. Proliferation pattern of postembryonic neuroblasts in the brain of Drosophila melanogaster. Dev Biol. 1992;149(1):134-148. Available from: https://doi.org/10.1016/0012-1606(92)90270-q
  22. Kato K, Awasaki T, Ito K. Neuronal programmed cell death induces glial cell division in the adult Drosophila brain. Development. 2009;136(1):51-59. Available from: https://doi.org/10.1242/dev.023366
  23. Li G, Forero MG, Wentzell JS, Durmus I, Wolf R, Anthoney NC, et al. A Toll-receptor map underlies structural brain plasticity. Elife. 2020;9. Available from: https://doi.org/10.7554/elife.52743
  24. Akers KG, Martinez-Canabal A, Restivo L, Yiu AP, De Cristofaro A, Hsiang HL, et al. Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science. 2014;344(6184):598-602. Available from: https://doi.org/10.1126/science.1248903
  25. Jacobs BL, Van Praag H, Gage FH. Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol Psychiatry. 2000;5(3):262-269. Available from: https://doi.org/10.1038/sj.mp.4000712
  26. Lois C, Garcia-Verdugo JM, Alvarez-Buylla A. Chain migration of neuronal precursors. Science. 1996;271(5251):978-981. Available from: https://doi.org/10.1126/science.271.5251.978
  27. Ming GL, Song H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron. 2011;70(4):687-702. Available from: https://doi.org/10.1016/j.neuron.2011.05.001
  28. Abdissa D, Hamba N, Gerbi A. Review article on adult neurogenesis in humans. Transl Res Anat. 2020;20:100074. Available from: https://doi.org/10.1016/j.tria.2020.100074
  29. Sierra A, Encinas JM, Maletic-Savatic M. Adult human neurogenesis: from microscopy to magnetic resonance imaging. Front Neurosci. 2011;5:47. Available from: https://doi.org/10.3389/fnins.2011.00047
  30. Bhardwaj RD, Curtis MA, Spalding KL, Buchholz BA, Fink D, Björk-Eriksson T, et al. Neocortical neurogenesis in humans is restricted to development. Proc Natl Acad Sci U S A. 2006;103(33):12564-12568. Available from: https://doi.org/10.1073/pnas.0605177103
  31. Spalding KL, Bhardwaj RD, Buchholz BA, Druid H, Frisén J. Retrospective birth dating of cells in humans. Cell. 2005;122(1):133-143. Available from: https://doi.org/10.1016/j.cell.2005.04.028
  32. Van Praag H, Shubert T, Zhao C, Gage FH. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci. 2005;25(38):8680-8685. Available from: https://doi.org/10.1523/jneurosci.1731-05.2005
  33. Novotny E, Ashwal S, Shevell M. Proton magnetic resonance spectroscopy: an emerging technology in pediatric neurology research. Pediatr Res. 1998;44(1):1-10. Available from: https://doi.org/10.1203/00006450-199807000-00001
  34. Manganas LN, Zhang X, Li Y, Hazel RD, Smith SD, Wagshul ME, et al. Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science. 2007;318(5852):980-985. Available from: https://doi.org/10.1126/science.1147851
  35. Riddle DR, Lichtenwalner RJ. Neurogenesis in the adult and aging brain. Brain Aging. 2007:127-158. Available from: https://www.ncbi.nlm.nih.gov/books/NBK3874/
  36. Toda T, Parylak SL, Linker SB, Gage FH. The role of adult hippocampal neurogenesis in brain health and disease. Mol Psychiatry. 2019;24(1):67-87. Available from: https://doi.org/10.1038/s41380-018-0036-2
  37. Mizuta K, Sato M. Multiphoton imaging of hippocampal neural circuits: techniques and biological insights into region-, cell-type-, and pathway-specific functions. Neurophotonics. 2024;11(3):033406. Available from: https://doi.org/10.1117/1.nph.11.3.033406
  38. Chen L, Cummings KA, Mau W, Zaki Y, Dong Z, Rabinowitz S, et al. The role of intrinsic excitability in the evolution of memory: Significance in memory allocation, consolidation, and updating. Neurobiol Learn Mem. 2020;173:107266. Available from: https://doi.org/10.1016/j.nlm.2020.107266
  39. Abrous DN, Wojtowicz JM. Interaction between neurogenesis and hippocampal memory system: new vistas. Cold Spring Harb Perspect Biol. 2015;7(6). Available from: https://doi.org/10.1101/cshperspect.a018952
  40. Yau SY, Li A, So KF. Involvement of adult hippocampal neurogenesis in learning and forgetting. Neural Plast. 2015;2015:717958. Available from: https://doi.org/10.1155/2015/717958
  41. Anacker C, Hen R. Adult hippocampal neurogenesis and cognitive flexibility—linking memory and mood. Nat Rev Neurosci. 2017;18(6):335-346. Available from: https://doi.org/10.1038/nrn.2017.45
  42. Palanisamy CP, Pei J, Alugoju P, Anthikapalli NV, Jayaraman S, Veeraraghavan VP, et al. New strategies of neurodegenerative disease treatment with extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs). Theranostics. 2023;13(12):4138-4165. Available from: https://doi.org/10.7150/thno.83066
  43. Culig L, Chu X, Bohr VA. Neurogenesis in aging and age-related neurodegenerative diseases. Ageing Res Rev. 2022;78:101636. Available from: https://doi.org/10.1016/j.arr.2022.101636
  44. Kim MY, Kim MJ, Lee C, Lee J, Kim SS, Hong S, et al. Trametinib activates endogenous neurogenesis and recovers neuropathology in a model of Alzheimer’s disease. Exp Mol Med. 2023;55(10):2177-2189. Available from: https://doi.org/10.1038/s12276-023-01073-2
  45. Jastrzębski MK, Wójcik P, Stępnicki P, Kaczor AA. Effects of small molecules on neurogenesis: neuronal proliferation and differentiation. Acta Pharm Sin B. 2023 Oct 20. [Epub ahead of print]. Available from: https://doi.org/10.1016/j.apsb.2023.10.015
  46. Liu Y, Chu JM, Yan T, Zhang Y, Chen Y, Chang RC, et al. Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer’s disease mice. J Neuroinflammation. 2020;17:4. Available from: https://doi.org/10.1186/s12974-019-1653-7
  47. Özbeyli D, Sarı G, Özkan N, Karademir B, Yüksel M, Kaya ÖT, et al. Protective effects of different exercise modalities in an Alzheimer’s disease-like model. Behav Brain Res. 2017;328:159-77. Available from: https://doi.org/10.1016/j.bbr.2017.03.044
  48. Martini F, Régis Leite M, Gonçalves Rosa S, Pregardier Klann I, Wayne Nogueira C. Strength exercise suppresses STZ-induced spatial memory impairment and modulates BDNF/ERK-CAMKII/CREB signaling pathway in the hippocampus of mice. Cell Biochem Funct. 2020;38(2):213-221. Available from: https://doi.org/10.1002/cbf.3470
  49. Farzi MA, Sadigh-Eteghad S, Ebrahimi K, Talebi M. Exercise improves recognition memory and acetylcholinesterase activity in the beta amyloid-induced rat model of Alzheimer’s disease. Ann Neurosci. 2019;25(3):121-125. Available from: https://doi.org/10.1159/000488580
  50. Bonanni R, Cariati I, Tarantino U, D’Arcangelo G, Tancredi V. Physical exercise and health: a focus on its protective role in neurodegenerative diseases. J Funct Morphol Kinesiol. 2022;7(2):38. Available from: https://doi.org/10.3390/jfmk7020038
  51. Latchney SE, Eisch AJ. Therapeutic application of neural stem cells and adult neurogenesis for neurodegenerative disorders: regeneration and beyond. Eur J Neurodegener Dis. 2012;1(3):335-51. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC4340249/
  52. Kang E, Wen Z, Song H, Christian KM, Ming GL. Adult neurogenesis and psychiatric disorders. Cold Spring Harb Perspect Biol. 2016;8(9). Available from: https://doi.org/10.1101/cshperspect.a019026
  53. Apple DM, Fonseca RS, Kokovay E. The role of adult neurogenesis in psychiatric and cognitive disorders. Brain Res. 2017;1655:270-276. Available from: https://doi.org/10.1016/j.brainres.2016.01.023
  54. Alonso M, Petit AC, Lledo PM. The impact of adult neurogenesis on affective functions: of mice and men. Mol Psychiatry. 2024;29(8):2527-2542. Available from: https://doi.org/10.1038/s41380-024-02504-w
  55. Campbell S, MacQueen G. The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci. 2004;29(6):417-426. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC524959/
  56. Cui L, Li S, Wang S, Wu X, Liu Y, Yu W, et al. Major depressive disorder: hypothesis, mechanism, prevention, and treatment. Sig Transduct Target Ther. 2024;9:30. Available from: https://doi.org/10.1038/s41392-024-01738-y
  57. Mumtaz F, Khan MI, Zubair M, Dehpour AR. Neurobiology and consequences of social isolation stress in animal model—a comprehensive review. Biomed Pharmacother. 2018;105:1205-1222. Available from: https://doi.org/10.1016/j.biopha.2018.05.086
  58. Petković A, Chaudhury D. Encore: behavioural animal models of stress, depression, and mood disorders. Front Behav Neurosci. 2022;16:931964. Available from: https://doi.org/10.3389/fnbeh.2022.931964
  59. Dieni CV, Gonzalez JC, Overstreet-Wadiche L. Multifaceted circuit functions of adult-born neurons. F1000Res. 2019;8. Available from: https://doi.org/10.12688/f1000research.20642.1
  60. Ghosh HS. Adult neurogenesis and the promise of adult neural stem cells. J Exp Neurosci. 2019;13:1179069519856876. Available from: https://doi.org/10.1177/1179069519856876
  61. Jones KL, Zhou M, Jhaveri DJ. Dissecting the role of adult hippocampal neurogenesis towards resilience versus susceptibility to stress-related mood disorders. npj Sci Learn. 2022;7(1):16. Available from: https://doi.org/10.1038/s41539-022-00133-y
  62. Lampada A, Taylor V. Notch signaling as a master regulator of adult neurogenesis. Front Neurosci. 2023 Jun 29;17:1179011. Available from: https://doi.org/10.3389/fnins.2023.1179011
  63. Hussain G, Akram R, Anwar H, Sajid F, Iman T, Han HS, et al. Adult neurogenesis: a real hope or a delusion?. Neural Regen Res. 2024;19(1):6-15. Available from: https://doi.org/10.4103/1673-5374.375317
  64. Tsujimura K, Shiohama T, Takahashi E. microRNA biology on brain development and neuroimaging approach. Brain Sci. 2022;12(10):1366. Available from: https://doi.org/10.3390/brainsci12101366
  65. Mohammed OA, Elballal MS, El-Husseiny AA, Khidr EG, El Tabaa MM, Elazazy O, et al. Unraveling the role of miRNAs in the diagnosis, progression, and therapeutic intervention of Parkinson’s disease. Pathol Res Pract. 2023:155023. Available from: https://doi.org/10.1016/j.prp.2023.155023
  66. Kim TA, Syty MD, Wu K, Ge S. Adult hippocampal neurogenesis and its impairment in Alzheimer’s disease. Zool Res. 2022 May 5;43(3):481-96. Available from: https://doi.org/10.24272/j.issn.2095-8137.2021.479
  67. Phillips C. Lifestyle modulators of neuroplasticity: how physical activity, mental engagement, and diet promote cognitive health during aging. Neural Plast. 2017;2017(1):3589271. Available from: https://doi.org/10.1155/2017/3589271
  68. Mandolesi L, Polverino A, Montuori S, Foti F, Ferraioli G, Sorrentino P, et al. Effects of physical exercise on cognitive functioning and wellbeing: biological and psychological benefits. Front Psychol. 2018;9:509. Available from: https://doi.org/10.3389/fpsyg.2018.00509
  69. Hullinger R, O’Riordan K, Burger C. Environmental enrichment improves learning and memory and long-term potentiation in young adult rats through a mechanism requiring mGluR5 signaling and sustained activation of p70s6k. Neurobiol Learn Mem. 2015;125:126-34. Available from: https://doi.org/10.1016/j.nlm.2015.08.006
  70. Zentall TR. Effect of environmental enrichment on the brain and on learning and cognition by animals. Animals. 2021 Mar 31;11(4):973. Available from: https://doi.org/10.3390/ani11040973
  71. Schoenfeld TJ, Gould E. Stress, stress hormones, and adult neurogenesis. Exp Neurol. 2012;233(1):12-21. Available from: https://doi.org/10.1016/j.expneurol.2011.01.008
  72. Ramírez-Rodríguez GB, Vega-Rivera NM, Meneses-San Juan D, Ortiz-López L, Estrada-Camarena EM, Flores-Ramos M. Short daily exposure to environmental enrichment, fluoxetine, or their combination reverses deterioration of the coat and anhedonia behaviors with differential effects on hippocampal neurogenesis in chronically stressed mice. Int J Mol Sci. 2021;22(20):10976. Available from: https://doi.org/10.3390/ijms222010976
  73. Llorente V, Velarde P, Desco M, Gómez-Gaviro MV. Current understanding of the neural stem cell niches. Cells. 2022;11(19):3002. Available from: https://doi.org/10.3390/cells11193002
  74. Liu B, Li Y, Ren M, Li X. Targeted approaches to delineate neuronal morphology during early development. Front Cell Neurosci. 2023;17:1259360. Available from: https://doi.org/10.3389/fncel.2023.1259360
  75. Hassan AU, Hassan G, Rasool Z. Role of stem cells in treatment of neurological disorder. Int J Health Sci. 2009 Jul;3(2):227-33. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC3068820/
  76. Pinosanu LR, Wolff N, Olaru DG, Popa-Wagner A. Stem cell treatments in preclinical relevant stroke models. Curr Health Sci J. 2023;49(4):487-494. Available from: https://doi.org/10.12865/chsj.49.04.02
  77. Nalamolu KR, Chelluboina B, Fornal CA, Challa SR, Pinson DM, Wang DZ, et al. Stem cell treatment improves post stroke neurological outcomes: a comparative study in male and female rats. Stroke Vasc Neurol. 2021;6(4):519-527. Available from: https://doi.org/10.1136/svn-2020-000834
  78. Sadanandan N, Saft M, Gonzales-Portillo B, Borlongan CV. Multipronged attack of stem cell therapy in treating the neurological and neuropsychiatric symptoms of epilepsy. Front Pharmacol. 2021;12:596287. Available from: https://doi.org/10.3389/fphar.2021.596287
  79. de Oliveira CL, Bolzan JA, Surget A, Belzung C. Do antidepressants promote neurogenesis in adult hippocampus? A systematic review and meta-analysis on naive rodents. Pharmacol Ther. 2020;210:107515. Available from: https://doi.org/10.1016/j.pharmthera.2020.107515

Figures:

Figure 1

Figure 1

Figure 1

Figure 2

Similar Articles

Recently Viewed

Read More

Most Viewed

Read More

Help ?