Neurogenesis

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‎Neurogenesis‎‎, or the formation of new ‎‎neurons‎‎, takes place not only in ‎‎the prenatal period‎‎ but also in ‎‎the brain of an‎‎ adult.‎

History[edit | edit source]

The first finding of neuroblasts was in 1960 by Altman in the brain of an adult rat.[1] However, without further doubt, neurogenesis was accepted when Fernando Nottebohm showed that in the hippocampus the canary neurogenesis takes place to a greater extent during the mating season, when new songs are learned.[2] In the following years, research was focused on the mechanisms of regeneration of the central nervous system (CNS). In 1998, Swede Peter S. Eriksson provided the first evidence of newly emerging neurons in the human brain.[3]

It was a post-mortem analysis of the brains of patients who were applied to the method of labelling proliferating cells, using bromodeoxyuridine (BrdU). See the illustrative image on the right. Since then, scientists have been searching for how neurogenesis takes place under both physiological and pathological conditions, where understanding the mechanisms could help in the treatment of certain diseases.

Neurogenesis in adults[edit | edit source]

  • It takes place in neurogenic areas. It is conditioned by the presence of neuronal stem cells (NSCs = neural stem cells), a specific microenvironment and neurogenic potential, i.e. the ability to differentiate into neurons.
  • There are a total of three main neurogenic areas in the mammalian brain. In the reactively neurogenic region, neurogenesis can only be induced experimentally, then a potentially neurogenic region where neuronal precursors are present, and finally three areas of constitutive neurogenesis where neurogenesis occurs continuously.[4] Some studies indicate the presence of a small number of progenitor cells in the spinal cord, midbrain, striatum and cerebral cortex.[5]

Areas of constitutive neurogenesis[edit | edit source]

Neurogenesis occurs continuously in only three areas of the adult brain – in the subgranular zone (SGZ = subgranular zone) in the dentate gyrus (DG = dentate gyrus) of the hippocampus, in the posterior periventricular area (PPv = posterior periventricular area), where NSCs are located under the ependymal cells that surround the hippocampus, and in the subventricular zone (SVZ = subventricular zone) on the lateral parts of the lateral ventricles of the forebrain.[6]

Subgranular and posterior periventricular zone[edit | edit source]

NSCs in the hippocampal dentate gyrus have only a limited ability for neurogenesis compared to the subventricular zone. These neuronal progenitors are located near the hilum DG, where they form a thin layer of cells between the hilum DG and the granular cell layer (GLC).[7] The subgranular zone is not in contact with the cerebrospinal fluid. There are radial astrocytes that have a pyramidal shape and long radial projections protruding through a layer of granular cells to the surface of DG. They constantly proliferate and the newly formed cells migrate to the GCL.

Similar to SVZ, DG precursors also express the glial fibrillar acidic protein (GFAP = glial fibrillary acidic protein) and these cells are considered primary progenitors of SGZ.[8] However, some studies are inclined to believe that there are two distinct types of progenitor cells present in SGZ, from which glia and neurons are formed separately.[9]

In DG, with the passage of age, cell proliferation decreases, which indicates that the self-renewal of cells is not eternal.[10] Multiple studies also confirm that A-cells, or neuroblasts, migrate to GCL to differentiate into granular cells.[11]

There are also horizontal astrocytes in SGZ that lack radial projections.[12] They behave like stem cells in vivo and may have the properties of hippocampus progenitor cells similar to radial astrocytes. In addition, they can divide asymmetrically and thus produce neurons. Their daughter cells can also acquire radial morphology.[13] Despite this new formation, most of the newly proliferating DG cells will soon die if they do not form the right synaptic connections.[14]

Subventricular zone[edit | edit source]

SVZ cell types[edit | edit source]

Regulation of neurogenesis[edit | edit source]

Functional significance of neurogenesis[edit | edit source]

Neurogenesis after cerebral ischemia[edit | edit source]

Links[edit | edit source]

Související články[edit | edit source]

External links[edit | edit source]


Source[edit | edit source]

Reference[edit | edit source]

  1. ↑ Altman, J. (1962): "Are neurons formed in the brains of adult mammals?" Science 135:1127-1128. [1]
  2. ↑ Nottebohm, F. (1981): "A brain for all seasons: cyclical anatomical changes in song control nuclei of the canary brain" Science 214:1368-1370.[2]
  3. ↑ Eriksson, P. S., E. Perfilieva, et al. (1998): "Neurogenesis in the adult human hippocampus." Nat Med 4: 1313-7[3]
  4. ↑ Ortega-Perez, I., K. Murray, et al. (2007): "The how and why of adult neurogenesis?" J Mol Histol 38: 555-62.
  5. ↑ Weiss, S. et al. (1996): "Mulltipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis." J. Neurosci. 16: 7599-7609; Nguyen, L. et al. (2006): "Coupling cell cycle exit, neuronal differentiation and migration in cortical neurogenesis." Cell Cycle 5: 2314-2318
  6. ↑ Wiltrout, C., B. Lang, et al. (2007). "Repairing brain after stroke: a review on post-ischemic neurogenesis." Neurochem Int 50: 1028-1041.
  7. ↑ Cameron,H.A., McKay,R.D.(2001): "Adult neurogenesis produces a large pol of new granule cells in the dentate gyrus." J. Comp. Neurol. 435: 406-417.
  8. ↑ Seri, B.,J.M. Gracia-Verdugo, et al. (2001): "Astrocyte give rise to new neurons in the adult mammalian hippocampus." J Neurosci 21: 7153-7160; Namba, T. et al. (2005): "The fate of neural progenitor cells expressing astrocytic and radial glial markers in the postantal rat dentate gyrus." Eur. J. Neurosci 22: 1928-1941
  9. ↑ Seaberg, R.m., van der Kooy, D. (2003): "Stem and progenitor cells: the premature desertion of rigorous definitions" Trends Neurosci 26: 125-131.
  10. ↑ Kuhn, H.G. et al. (1996): "Neurogenesis in the dentate gyrus of the adult rat: age related decrease of neuronal porgenitor proliferation." J Neurosci 16: 2027-2033
  11. ↑ Overstreer Wadiche, L.S., Westbrook, G.L. (2006): "Functional maturation of adult generated granule cells." Hippocampus 16: 208-215
  12. ↑ Seri, B., J.M. Garcia-Verdugo (2004): "Cell types, lineage, and architecture of the germinal zone in the adult dentate gyrus." J Comp Neurol 478: 359-378
  13. ↑ Suh, H., A. Consiglio, et al.(2007): "In vivo fate analysis reveals the multipotent and selfrenewal capacities of Sox2+ neural stem cells in the adult hippocampus." Cell Stem Cell 1: 515-528.
  14. ↑ Gould, E. et al(2001): "Adult generated hippocampal and neocortical neurons in macaques have a transient existence." Proc. Natl. Acad. Sci. U.S.A. 98: 10910-10917

Literature used[edit | edit source]

Recommended reading[edit | edit source]

  • Fred Gage, Gerd Kempermann, Hongjun Song: Adult neurogenesis, Cold Spring Harbor Laboratory 2008.[4]
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