Neurogenesis

from Wikipedia, the free encyclopedia

As neurogenesis , the formation of nerve cells from certain stem designated or progenitor cells. A distinction is made according to the development phase in addition to the neurogenesis during embryonic and fetal period between the early postnatal and adult neurogenesis.

Neurogenesis during embryonic development

During embryogenesis, the cerebral cortex is built up in layers from the ventricular system. This first creates nerve cells that migrate along the extensions of so-called radial glial cells towards the surface of the brain, thus building up the cortex.

Adult neurogenesis

Until the 1990s, neurogenesis in the adult human central nervous system (CNS) was considered to be ruled out, even if it was known that some songbirds , among other things, could continue to form nerve cells even after sexual maturity . For example, neurogenesis in songbirds plays an essential role in learning and refining mating songs. More recent studies on neurogenesis, however, show that in humans, as in other mammals, neuronal stem cells can multiply and new nerve cells can form even in old age. In many mammals (including rats and mice) it has been shown that this new formation is dependent on both mental and physical activity. It is believed that adult neurogenesis is also regulated in a similar way in humans. Due to their remarkable adaptability and plasticity , the young cells change the processing of information in certain regions of the brain such as the hippocampus .

Adult neurogenesis in the hippocampus

Adult neurogenesis takes place in the hippocampus in the area of ​​the dentate gyrus , more precisely in the subgranular zone, which lies between the hilus and granule cell layer . This is where the cell bodies of neuronal stem cells are located , the apical dendrites of which extend into the molecular cell layer .

Neural stem cells have a high density of voltage- independent K + channels and no voltage-dependent Na + channels and are therefore not electrically excitable. Morphologically, they resemble radial astroglial cells (marker proteins: GFAP , nestin ). The neural stem cells have the ability to generate new cells through asymmetric mitotic division (ability to proliferate ). These newly created cells are called neuronal precursor cells ( progenitor cells ).

The neural progenitor cells, which also have a time-limited ability to proliferate (in this time window of fewer days, they have a significantly higher rate of division than neural stem cells), differ morphologically from neural stem cells, among other things due to the loss of the marker protein GFAP.

The regulation of the division rate takes place on different levels. On the one hand, "stress factors" such as cortisol have an inhibiting effect on the rate of division, on the other hand, an increase in the rate of division has been demonstrated, among other things, by growth factors such as IGF-1 and VEGF , which is based on a connection between the rate of neurogenesis and physical activity.

In the neuronal progenitor cells, there is an early expression of NKCC1 transporters (Na + -K + -2Cl - - cotransporters ), which generates a high intracellular Cl - concentration. This results in that the first almost exclusively GABAergic synaptic inputs show an excitatory postsynaptic effect as early known GABA A receptors - which otherwise commonly an inhibitory postsynaptic potential ( IPSP generate) - due to the high intracellular Cl - concentration a Cl - - Initiate outflow from the cell, which leads to a depolarization of the membrane.

As a result of the depolarization, voltage-dependent calcium channels are temporarily opened and thus a Ca 2+ influx into the cell. The increased Ca 2+ concentration in turn can initiate growth processes as an intracellular signal, which initiate the formation of early neuronal proteins such as voltage-dependent Na + channels or induce synaptic plasticity . Most of the newly formed cells in the dentate gyrus develop into neurons ( neuronal determination ).

The induction of synaptic plasticity and early integration into the CNS are essential for the survival of young neurons. Only cells that are integrated and involved in the neural network of the hippocampus at an early stage do not die, but rather form the dendritic tree with numerous thorns typical of granule cells in about four weeks ( maturation phase ). About two weeks after the mitotic division of the neural stem cell, newly formed axons can already be found in the CA3 region of the hippocampus. At this time, NKCC1 transporters are replaced by KCC2 transporters (K + -Cl - cotransporters), which leads to a decrease in the intracellular Cl - concentration, so that GABA has an inhibitory effect in the second half of the maturation phase. At this time, the young neurons experience the first glutamatergic synaptic inputs, which forms the basis of synaptic plasticity ( LTP and LTD ) through NMDA and AMPA receptors . About four weeks after the mitotic division of the neural stem cell, no more morphological or electrophysiological differences to neighboring neurons can be determined.

Regions of neurogenesis

It has been shown in primates such as the rhesus monkey ( Macaca mulatta ) that new nerve cells form in them in the subventricular zone . These young neurons then migrate along fixed paths into the cortex , where they mature, form axons and synapses , and integrate into the brain's neural network.

Only later did it become apparent that even in the human brain, neurogenesis still takes place to a small extent after puberty . This applies not only to the primary sensory cells of the olfactory epithelium , the olfactory cells , which are also neurons and renew themselves based on neurogenic basal cells. Even in the human subventricular zone of the adult there are still neural stem cells that are able to produce new nerve cells. In addition, adult neurogenesis occurs primarily in certain regions of the hippocampus . Mediator molecules known as neurotrophins or nerve growth factors are involved in these processes .

see also: Semaphorine

Function of neurogenesis

In general, little is known about the function of newly formed nerve cells. In the hippocampus, newly formed granule cells seem to have a function in the formation or consolidation of long-term memory . The statements made so far are essentially based on animal models from neuroscience (as in the case of the mouse).

In humans, processes of neurogenesis seem v. a. to be moderated by chronic stress and the central hypothalamic-pituitary-adrenal axis ( HHNA ). This takes place within the framework of the allostasis reaction, which is ascribed an essential role in adapting to changing environmental and living conditions.

Therapeutic use

Great hopes are placed in neurogenesis for the healing of diseases and injuries to the central nervous system .

literature

  • Jörg Blech : Brain, cure yourself! . In: Der Spiegel . 20, 2006, pp. 164-178.
  • Y. Chen, Y. Ai, JR Slevin, BE Maley, DM Gash: Progenitor proliferation in the adult hippocampus and substantia nigra induced by glial cell line-derived neurotrophic factor. In: Experimental neurology. 196 (1), 2005, pp. 87-95.
  • JG Emsley, BD Mitchell, G. Kempermann, JD Macklis: Adult neurogenesis and repair of the adult CNS with neural progenitors, precursors and stem cells In:. Progress in Neurobiology. 75 (5), 2005, pp. 321-341.
  • Fred H. Gage , G. Kempermann, H. Song (Eds.): Adult Neurogenesis . Cold Spring Harbor Laboratory Press, 2008, ISBN 978-0-87969-784-6 .
  • Gerd Kempermann: Adult Neurogenesis. Stem Cells and Neuronal Development in the Adult Brain . Oxford University Press , 2006, ISBN 0-19-517971-4 .
  • GL Ming, H. Song: Adult neurogenesis in the mammalian central nervous system. In: Annual review of neuroscience. 28, 2005, pp. 223-250.
  • C. Zhao, W. Deng, FH Gage: Mechanisms and functional implications of adult neurogenesis In: Cell . 132 (4), 2008, pp. 645-660.
  • E. Gould: How widespread is adult neurogenesis in mammals? In: Nature Reviews Neuroscience . 8 (6), 2007, pp. 481-488.
  • Jason S. Snyder: Questioning human neurogenesis . Nature (March 07, 2018) ( www.nature.com )

Individual evidence

  1. Tracey J. Shors: To be or not to be in the brain. In: Spectrum of Science No. 8, 2010 , p. 35.
  2. What is neurogenesis? www.news-medical.net
  3. ^ A b c Josef Bischofberger, Christoph Schmidt-Hieber: Adult neurogenesis in the hippocampus. In: Perspectives on Brain Research - Neuroforum. No. 3, 2006 (PDF file; 4.82 MB), p. 214.
  4. a b c d Josef Bischofberger, Christoph Schmidt-Hieber: Adult neurogenesis in the hippocampus. In: Perspectives on Brain Research - Neuroforum. No. 3, 2006 (PDF file; 4.82 MB), p. 215.
  5. Tracey J. Shors: To be or not to be in the brain. In: Spectrum of Science. No. 8, 2010 , p. 37.
  6. ^ A b Josef Bischofberger, Christoph Schmidt-Hieber: Adult neurogenesis in the hippocampus. In: Perspectives on Brain Research - Neuroforum. No. 3, 2006 (PDF file; 4.82 MB), p. 217.
  7. ^ P. Sterling, J. Eyer: Allostasis: a new paradigm to explain arousal pathology. In: S. Fisher, J. Reason (Eds.): Handbook of life stress, cognition and health. Wiley & Sons, New York 1988, pp. 631-651.
  8. G. Hüther: Biology of fear - how feelings become from stress. Vandenhoeck & Ruprecht, Göttingen 1997, ISBN 3-525-01439-2 .
  9. P. Sterling: Allostasis: a model of predictive regulation. In: Physiol Behav. 106, 2012, pp. 5-15. doi: 10.1016 / j.physbeh.2011.06.004

Web links

Commons : Neurogenesis  - collection of images, videos and audio files