Neurogenesis

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Neurogenesis (birth of neurons) is the process by which neurons are created(Gage,2003;Mohapel,Leanza,Kokaia&Lindvall,2006;Prickaerts,Koopmans,Blockland&Scheepens,2004). Most active during pre-natal development, neurogenesis is responsible for populating the growing brain.

The discovery of adult neurogensis raises new possibilities in the treatment of neurological disorders and brain and spinal cord injuries (Van Praag,Zhao,&Gage,2004).

Adult Neurogenesis

New neurons are continually born throughout adulthood in predominantly two regions of the brain:

• The sub-ventricular zone lining the lateral ventricles, where the new cells migrate to the olfactory bulb via the Rostral Migratory Stream
• The dentate gyrus of the hippocampus.

Many of these newborn cells die shortly after their birth, but a number of them become functionally integrated into the surrounding brain tissue.

Adult neurogenesis has been the subject of an historical dogma, and only recently has its existence been largely accepted by the scientific community. While it is reasonably well-accepted that hippocampal neurogenesis does occur (see for example Eriksson et al., 1998; Gould et al., 1999a), some authors (particularly Elizabeth Gould) have suggested that adult neurogenesis may also occur in other areas including human neocortex (e.g., Gould et al., 1999b; Zhao et al., 2003). Others, including Rakic (2002), have questioned the scientific evidence of these findings; in the broad sense, they suggest that the new cells may be glia.

The function of adult neurogenesis is not certain [1] - although there is good evidence that hippocampal adult neurogenesis is important for learning and memory. This is perhaps unsurprising given what we know of the hippocampus and its role in learning and memory (several authors, including, for example, Rolls & Treves (1998) have postulated integrated theories for the role of hippocampus in learning and memory). Gould et al. (1999c) have demonstrated that the act of learning itself is associated with increased neuronal survival.

Malberg et al. (2000) [2] and Manev et al. (2001) [3] have linked neurogenesis to the beneficial actions of certain antidepressants, suggesting a connection between decreased hippocampal neurogenesis and depression. In a subsequent paper, Santarelli et al. (2003) demonstrated that the behavioural effects of antidepressants in rats did not occur when neurogenesis was prevented with x-irradiation techniques. Very recent papers have linked together learning and memory with depression, and have suggested that neurogenesis may promote neuroplasticity. For instance, Castren (2005) has proposed that our mood may be regulated, at a base level, by plasticity, and so chemistry; for instance, the effects of antidepressant treatment is only secondary to this.

Various other factors may increase or decrease rates of hippocampal neurogenesis. Even voluntary exercise (e.g., Bjornebekk, Mathe & Brene, 2005) seems to promote their survival and successful integration into the existing hippocampus. On the other hand, stimuli such as chronic stress can decrease their proliferation. The link between stress, depression, and the hippocampus is well-documented (e.g., Lee et al., 2002; Sheline et al., 1999).

Adult neural stem cells

Neural stem cells (NSCs) are the self-renewing, multipotent cells that generate the main phenotypes of the nervous system. In 1992, Reynolds and Weiss were the first to isolate neural progenitor and stem cells from the striatal tissue, including the subventricular zone – one of the neurogenic areas - of adult mice brain tissue (Reynolds & Weiss, 1992) [4]. Since then, neural progenitor and stem cells have been isolated from various areas of the adult brain, including non-neurogenic areas, such as the spinal cord, and from various species including human (Taupin & Gage, 2002) [5]. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) are mitogens for neural progenitor and stem cells in vitro, though other factors synthesized by the neural progenitor and stem cells in culture are required for their growth (Taupin et al., 2000) [6] . It is hypothesized that neurogenesis in the adult brain originates occurs from NSCs. The origin and identity of NSCs in the adult brain remain to be defined.

See also

Brain healing

References

• Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH. (1998) Neurogenesis in the adult human hippocampus. Nat Med. Nov;4(11):1313-7. PMID 9809557
• Gould E, Reeves AJ, Fallah M, Tanapat P, Gross CG, Fuchs E. (1999a). Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci U S A. Apr 27;96(9):5263-7. PMID 10220454
• Gould E, Reeves AJ, Graziano MS, Gross CG. (1999b). Neurogenesis in the neocortex of adult primates. Science. Oct 15;286(5439):548-52. PMID 10521353
• Zhao M, Momma S, Delfani K, Carlen M, Cassidy RM, Johansson CB, Brismar H, Shupliakov O, Frisen J, Janson AM (2003). Evidence for neurogenesis in the adult mammalian substantia nigra. Proc Natl Acad Sci U S A. Jun 24;100(13):7925-30. PMID 12792021
• Rakic P. Neurogenesis in adult primate neocortex: an evaluation of the evidence. (2002). Nat Rev Neurosci. Jan;3(1):65-71. PMID 11823806
• Rolls, E.T & Treves, A. (1998). Neural Networks and Brain Function. Oxford: OUP. ISBN 0-19-852432-3.
• Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ. (1999c). Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci. Mar;2(3):260-5. PMID 10195219
• Malberg JE, Eisch AJ, Nestler EJ, Duman RS. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci. 2000 Dec 15;20(24):9104-10.Fulltext
• Manev H, Uz T, Smalheiser NR, Manev R. Antidepressants alter cell proliferation in the adult brain in vivo and in neural cultures in vitro. Eur J Pharmacol. 2001 Jan 5;411(1-2):67-70.[7]
• Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R. (2003). Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. Aug 8;301(5634):805-9. PMID 12907793
• Castren E. (2005). Is mood chemistry?. Nat Rev Neurosci. Mar;6(3):241-6. PMID 15738959
• Bjornebekk A, Mathe AA, Brene S. (2005). The antidepressant effect of running is associated with increased hippocampal cell proliferation. Int J Neuropsychopharmacol. Sep;8(3):357-68. PMID 15769301
• Lee AL, Ogle WO, Sapolsky RM. (2002). Stress and depression: possible links to neuron death in the hippocampus. Bipolar Disord. Apr;4(2):117-28. PMID 12071509
• Sheline YI, Gado MH, Kraemer HC. (2003). Untreated depression and hippocampal volume loss. Am J Psychiatry. Aug;160(8):1516-8. PMID 12900317
• Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 1992 Mar 27;255(5052):1707-10. PMID 1553558. [8]
• Taupin P, Gage FH. Adult neurogenesis and neural stem cells of the central nervous system in mammals. J Neurosci Res. 2002 Sep 15;69(6):745-9. PMID 12205667. [9]
• Taupin P, Ray J, Fischer WH, Suhr ST, Hakansson K, Grubb A, Gage FH. FGF-2-responsive neural stem cell proliferation requires CCg, a novel autocrine/paracrine cofactor. Neuron. 2000 Nov;28(2):385-97. PMID 11144350. [10]
• Shors TJ, Mieseages G, Beylin A, Zhao M, Rydel T, Gould E (2001) Neurogenesis in the adult is involved in the formation of trace memories. Nature 410: 372-376.
• Gould E, Gross CG (2002) Neurogenesis in adult mammals: some progress and problems. The Journal of Neuroscience 22: 619-623.
• Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ (1999) Learning enhances adult neurogenesis in the hippocampal formation. Nature Neurosci 2: 260-265.
• Kempermann G, Brandon EP, Gage FH. (1998) Environmental stimulation of 129/SvJ mice causes increased cell proliferation and neurogenesis in the adult dentate gyrus. Curr Biol. 1998 Jul 30-Aug 13;8(16):939-42.

External links

• Seed magazine: The Reinvention of the Self - A historical background on the field of neurogenesis and implications of this research

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