Adult neurogenesis

Historical perspective[edit | edit source]

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"Adult Neurogenesis" refers to the ability of the central nervous system (brain and spinal cord) to generate new neurons in adulthood called adult generated neurons[1]. This is as differentiated from "neurogenesis" typically used to describe the processes of neuronal generation that occur during the prenatal (embryonic and fetal) period extending in to the early years of postnatal life.

Back in the 1800s and the first half of the 20th century, scientists and scholars believed that development of new neurons only occurred early in life and would cease at some point during development, so that no new neurons could be formed in the brain or spinal cord after this 'critical age'[2]. Some scientists back then disputed this as fact but had no means of disproving the widely accepted notion, the non-availability of advanced equipment back then and less advanced scientific investigation and laboratory techniques meant this notion would go unchallenged for a very long time.

Current opinions/Key evidence[edit | edit source]

In the 1960s, some very brave scientists began to use the more advanced techniques of that time to demonstrate that some mitotic figures could be identified in the brains of adult birds. This generated a lot of interest and a shift of focus was made to the mammalian species which were considered to be more advanced species and closer to the human being. adult neurogenesis was discovered in progressively higher orders of the mammalian species from the rodents (laboratory rats and mice) to the primates such as chimpanzees and monkeys. In 1998, a scientist by the name of Peter Ericksson and his team were the first to conclusively demonstrate that adult generated neurons could be identified in the human brain as well[3]. Two areas have been consistently identified across all species studied to date, which are the subgranular zone of the hippocampus (hippocampus is responsible for spatial memory) and the subventricular zone of the lateral ventricles (the area from which neurons migrate to form the cerebral hemispheres and cerebral cortex in the embryonic and fetal periods)[4][5].

In 2018, it was reported that neurogenesis in the dentate gyrus (DG) of the hippocampus of human brains persists into old age, however, this was deemed controversial by some scientists.[6][7]The contrasting results of studies by Boldrini et al[6] and Sorells et al[7]promoted the ambiguity already surrounding adult neurogenesis. In recent times, the no. of studies supporting neurogenesis in adults is on the rise albeit with results showing only minute changes in the hippocampal regions.[8]

Adult neurogenesis and neurological disease[edit | edit source]

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Immense interest has been generated around this area, now that adult neurogenesis is known to be a fact, focus has shifted towards determining the factors that affect adult neurogenesis (increase or decrease it rate of occurrence) and the functions of these adult generated neurons. Interestingly, it has been shown that such factors as physical exercise, living in an environmentally enriched area and mentally challenging tasks among other things improve the rate of production of new neurons in the adult hippocampus as well as increase the longevity of these newly generated neurons[9][10]. In the same vein, scientists have managed to demonstrate that laboratory animals in which the rates of neurogenesis had been increased by such means as physical exercise performed better at tasks such as learning a new skill or spatial navigation in a novel (new) environment[11]. Incidentally, elevated levels of adult hippocampal neurogenesis have been observed in adults with neurological insults and diseases such as stroke (CVA), Alzheimer's disease, Parkinson's disease, Huntington's disease and dementia amongst others[12]. These diseases are characterised by death and destruction of neurons and the elevated levels of neurogenesis are hypothesised to be the body's own way of trying to replace the neurons that would have been lost[13]

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Physiotherapist's role[edit | edit source]

Considering that physical exercise and environmental enrichment will improve the levels of adult neurogenesis, physiotherapists can augment the body's own regenerative capacities by working with patients with neurological diseases to promote activities that enhance hippocampal neurogenesis[6][8]. Studies have showed that exercise will enhance adult neurogenesis and show a positive change in the cognitive skills grossly[14][15]. Ways to achieve this include:
1. Promote a healthy lifestyle - eat healthy, avoid the use of drugs. The use of drugs such as methamphetamine decreases the rate of neurogenesis and decreases cognitive functions [16]

2. Develop an exercise regime as part of the treatment programme for neurological patients[14].

3. Promote a stress free environment physically and mentally.

[17]

Resources[edit | edit source]




References[edit | edit source]

  1. Cameron HA, Mckay RD. Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. Journal of Comparative Neurology. 2001 Jul 9;435(4):406-17
  2. Gross CG. Neurogenesis in the adult brain: death of a dogma. Nature Reviews Neuroscience. 2000 Oct 1;1(1):67-73.
  3. Eriksson PS, Perfilieva E, Björk-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH. Neurogenesis in the adult human hippocampus. Nature medicine. 1998 Nov 1;4(11):1313-7.
  4. Ming GL, Song H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron. 2011 May 26;70(4):687-702.
  5. Kempermann G, Gage FH, Aigner L, et al. Human adult neurogenesis: evidence and remaining questions. Cell Stem Cell. 2018;23(1):25–30.
  6. 6.0 6.1 6.2 Boldrini M, Fulmore CA, Tartt AN, et al. Human hippocampal neurogenesis persists throughout aging. Cell Stem Cell. 2018;22(4):589–599.e5.
  7. 7.0 7.1 Sorrells SF, Paredes MF, Cebrian-Silla A, et al. Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature. 2018;555(7696):377–381.
  8. 8.0 8.1 Kumar A, Pareek V, Faiq MA, Ghosh SK, Kumari C. ADULT NEUROGENESIS IN HUMANS: A Review of Basic Concepts, History, Current Research, and Clinical Implications. Innov Clin Neurosci. 2019 May 1;16(5-6):30-37. PMID: 31440399; PMCID: PMC6659986.
  9. Van Praag H, Kempermann G, Gage FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nature neuroscience. 1999 Mar 1;2(3):266-70.
  10. Fabel K, Fabel K, Tam B, Kaufer D, Baiker A, Simmons N, Kuo CJ, Palmer TD. VEGF is necessary for exercise‐induced adult hippocampal neurogenesis. European Journal of Neuroscience. 2003 Nov 1;18(10):2803-12.
  11. Ehninger D, Kempermann G. Paradoxical effects of learning the Morris water maze on adult hippocampal neurogenesis in mice may be explained by a combination of stress and physical activity. Genes, Brain and Behavior. 2006 Feb 1;5(1):29-39.
  12. Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, Greenberg DA. Increased hippocampal neurogenesis in Alzheimer's disease. Proceedings of the National Academy of Sciences. 2004 Jan 6;101(1):343-7.
  13. Winner B, Winkler J. Adult neurogenesis in neurodegenerative diseases. Cold Spring Harb Perspect Biol. 2015 Apr 1;7(4):a021287. doi: 10.1101/cshperspect.a021287. PMID: 25833845; PMCID: PMC4382734.
  14. 14.0 14.1 Moreno-Jimenez EP, Flor-Garcia M, Terreros-Roncal J, Rabano A, Cafini F, Pallas-Bazarra N, Avila J, Llorens-Martin M. Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nat Med. 2019;25:554–560. doi: 10.1038/s41591-019-0375-9.
  15. Lei X, Wu Y, Xu M, Jones OD, Ma J, Xu X. Physical exercise: bulking up neurogenesis in human adults. Cell Biosci. 2019 Sep 3;9:74. doi: 10.1186/s13578-019-0337-4. PMID: 31508196; PMCID: PMC6724373.
  16. Van Praag H. Neurogenesis and exercise: past and future directions. Neuromolecular medicine. 2008 Jun 1;10(2):128-40.
  17. David Perlmutter MD. Neurogenesis. Available from: https://www.youtube.com/watch?v=h4NfYd4wq7o (last accessed 13.3.2019)