Neurogenesis in Adult Central Nervous System: Death of a Dogma
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1 Aristotle University of Thessaloniki, Greece, Nov Neurogenesis in Adult Central Nervous System: Death of a Dogma Anton B. Tonchev Division of Cell Biology, Varna University of Medicine, Bulgaria Department of Restorative Neurosurgery Kanazawa University, Japan
2 Neuroplasticity is a continuous process in reaction to neuronal activity and neuron injury, which involves modulation of structural and functional processes of axons, dendrites, and synapses.
3 Processes that manifest plasticity Synapses (electrical, biochemical, structural) Neurite (axon, dendrite) Neuron cell bodies Transport (anterograde and retrograde) Cell interactions (neuron - glia) Neural networks
4 Structural elements of plasticity Synaptic efficacy LTP remodeling genesis Neurite extension axonal sprouting dendritic remodeling Neurogenesis and recruitment
5 Structural elements of plasticity Cell division & neurogenesis Synaptogenesis presynaptic terminal neurite extension Synaptic efficacy & remodeling postsynaptic terminal
6
7 Ramon y Cajal (1928): Once development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably. In the adult centers the nerve paths are something fixed, ended and immutable. Everything must die, nothing may be regenerated. It is for the science of the future to change, if possible, this harsh decree.
8 Neural Stem Cells (Okano H, Keio Med J, 2002) Undifferentiated Proliferate Self-renew Generate descendants Regenerate tissue?
9 Neurogenesis Generation of neurons from stem/progenitor cells
10 SVZ Cellular architecture Stem cell Transit amplify ing cell 2 / 1 / 3 Neuronal progenitor Doetsch F The glial identity of neural stem cells. Nat Neurosci 6:
11 Migration to Olfactory Bulb O Rourke NA Neuron 16:
12 Human SVZ
13 Neural Progenitor Cells in Adult Brain Dennis A Steindler, David W Pincus Lancet 2002; 359: Gould et al., Proc Natl Acad Sci USA 1998; 95:
14 Anatomy of Primate Hippocampus Gyrus dentatus CA4 CA3 CA2 Entorhinal cortex CA1
15 Dentate Gyrus - Neurogenesis Progenitor Immature neuron Mature neuron
16 1d Gradual Maturation of New Neurons in DG 7d 21d Becker S, Wojtowicz JM, Trends Cogn Sci Feb;11(2):70-6
17 Functional Neurogenesis Dentate Gyrus (vanpraag et al, Nature, 2002)
18 Levels of Functional Analysis in Adult Neurogenesis Kempermann, Wiskott, Gage. Curr Opin Neurobiol 2004, 14:
19 Physiological Conditions Affecting Neurogenesis (Gyrus dentatus) Increased proliferation environmental enrichment, learning physical exercise Decreased proliferation ageing maternal separation
20 Drugs Affecting Neurogenesis (Gyrus dentatus) Increased proliferation antidepressants (TCA & SSRI); ECT haloperidol lithium estrogen, aldosterone inhibitory amino acids (GABA) Decreased proliferation corticosteroids opiates (morphine) excitatory amino acids (GLU)
21 Clinical Conditions Affecting Neurogenesis (Gyrus dentatus) Increased proliferation ischemia seizures trauma degeneration (dementia) Decreased proliferation stress (depression) irradiation inflammation (meningitis) chronic alcoholism
22 Multipotent progenitor FGF-2, EGF TGFα Epo SCF HB-EGF VEGF Shh IGF-I GDNF Proliferating progenitors LIF BMP IGF-I BDNF Astrocyte Oligodendrocyte Neuron
23 Evolution of the view of adult neurogenesis Gould E. Nat Rev Neurosci. 2007; 8:481-8.
24
25 Neurogenesis? Rodent = Monkey
26
27 Clinical Applications of Neural Progenitors Cerebral ischemic injury Neurodegenerative diseases Multiple sclerosis Brain tumors Congenital malformations Dennis A Steindler, David W Pincus Lancet 2002; 359:
28 Sources of Stem Cells for Transplantation Jakel et al,
29 Conclusions Endogenous progenitor cells reside in adult mammalian brain including that of primates Progenitor cells in respond to various environmental stimuli Progenitor cells are located in specific cellular niches Neurogenesis takes place in an angiogenic environment
30 Varna, Bulgaria Medical University - Varna
Brain ischemia, neurogenesis, and neurotrophic receptor expression in primates
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