Limits...
The aged brain: genesis and fate of residual progenitor cells in the subventricular zone.

Capilla-Gonzalez V, Herranz-Pérez V, García-Verdugo JM - Front Cell Neurosci (2015)

Bottom Line: This review provides a compilation of the current knowledge about the age-related changes in the NSC population, as well as the fate of the newly generated cells in the aged brain.It is known that the neurogenic capacity is clearly disrupted during aging, while the production of oligodendroglial cells is not compromised.Interestingly, the human brain seems to primarily preserve the ability to produce new oligodendrocytes instead of neurons, which could be related to the development of neurological disorders.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Comparative Neurobiology, Department of Cell Biology, Instituto Cavanilles de Biodiversidad y Biología Evolutiva, University of Valencia, CIBERNED Valencia, Spain ; Department of Stem Cells, Andalusian Center for Molecular Biology and Regenerative Medicine Seville, Spain.

ABSTRACT
Neural stem cells (NSCs) persist in the adult mammalian brain through life. The subventricular zone (SVZ) is the largest source of stem cells in the nervous system, and continuously generates new neuronal and glial cells involved in brain regeneration. During aging, the germinal potential of the SVZ suffers a widespread decline, but the causes of this turn down are not fully understood. This review provides a compilation of the current knowledge about the age-related changes in the NSC population, as well as the fate of the newly generated cells in the aged brain. It is known that the neurogenic capacity is clearly disrupted during aging, while the production of oligodendroglial cells is not compromised. Interestingly, the human brain seems to primarily preserve the ability to produce new oligodendrocytes instead of neurons, which could be related to the development of neurological disorders. Further studies in this matter are required to improve our understanding and the current strategies for fighting neurological diseases associated with senescence.

No MeSH data available.


Related in: MedlinePlus

Organization of the adult human SVZ. (A) Diagram representing the adult human SVZ. A monolayer of ependymal cells (Layer I) separates the lateral ventricle from the SVZ. Adjacent to it, a gap or hypocellular layer is mostly composed of GFAP+ cellular expansions (Layer II). Next to the gap layer, the astrocyte ribbon is represented (Layer III), continued by a transition zone to the brain parenchyma (Layer IV). (B) Electron microscopy coronal image of the human SVZ obtained from a 53-year-old female donor. Note the typical organization of this human neurogenic niche (Layers I to IV). b, astrocyte; e, ependymal cell; m, microglia. Scale bar: 4 μm.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4585225&req=5

Figure 4: Organization of the adult human SVZ. (A) Diagram representing the adult human SVZ. A monolayer of ependymal cells (Layer I) separates the lateral ventricle from the SVZ. Adjacent to it, a gap or hypocellular layer is mostly composed of GFAP+ cellular expansions (Layer II). Next to the gap layer, the astrocyte ribbon is represented (Layer III), continued by a transition zone to the brain parenchyma (Layer IV). (B) Electron microscopy coronal image of the human SVZ obtained from a 53-year-old female donor. Note the typical organization of this human neurogenic niche (Layers I to IV). b, astrocyte; e, ependymal cell; m, microglia. Scale bar: 4 μm.

Mentions: The organization of the adult human SVZ shows some divergences from the classical SVZ described for other mammalian species. In humans, the SVZ is composed by an ependymal layer (Layer I) that is in contact with the ventricular lumen. Next to this layer, there is a gap or hypocellular layer (Layer II), which is formed during postnatal development as a consequence of neuroblast depletion in this region. It is mostly populated by GFAP immunopositive cell expansions, although ependymal cells also send basal processes into this area. Adjacent to the hypocellular layer, there is a dense ribbon of cell bodies (Layer III) that contains astrocytes with a variable morphology, and is continued by a transition region (Layer IV) with few cells and similar to the underlying brain parenchyma (Figure 4). The human SVZ also acts as a NSCs niche capable of generating new neurons (Quinones-Hinojosa et al., 2006). During fetal and pediatric stages, SVZ-derived neuroblasts migrate via RMS into the OB (Sanai et al., 2004, 2011; van den Berge et al., 2010; Guerrero-Cazares et al., 2011). However, when the migration of neuroblasts to the OB was being studied in infants, it was unexpectedly found that there is another major migratory pathway of immature neurons destined for the prefrontal cortex (Sanai et al., 2011), suggesting that OB neurogenesis is less relevant in the human brain. In fact, the incorporation of new neurons into the human OB is nearly extinct by adulthood, as revealed by the measurement of 14C concentrations in the genomic DNA of these cells, which corresponded to the levels of atmospheric 14C at the time of birth of the examined individuals (Bergmann et al., 2012). Using the same birth dating approach, a recent study demonstrated that there is a postnatal cell turnover in the striatum of adult humans. This was corroborated by the incorporation of thymidine analog iododeoxyuridine (IdU) in striatal cells of cancer patients subjected to radiosensitization. Assessment of the expression of specific markers led these investigators to conclude that, new cells in the striatum correspond to neuronal and oligodendrocyte lineage cells (Ernst et al., 2014). Although authors suggested that these neurons likely derive from the SVZ, other origins cannot be excluded. In this regard, the production of new neurons in the adult human SVZ is still subject to debate. Most studies point to a dramatic decrease in DCX positive cells in the RMS and the OB from fetal to adult stages (Sanai et al., 2004; Wang et al., 2011). Moreover, other study demonstrated that most of the newly generated cells during adulthood correspond to non-neuronal cells, such as oligodendrocytes (Bergmann et al., 2012), suggesting that the oligodendrogenic process acquires more significance in the human brain.


The aged brain: genesis and fate of residual progenitor cells in the subventricular zone.

Capilla-Gonzalez V, Herranz-Pérez V, García-Verdugo JM - Front Cell Neurosci (2015)

Organization of the adult human SVZ. (A) Diagram representing the adult human SVZ. A monolayer of ependymal cells (Layer I) separates the lateral ventricle from the SVZ. Adjacent to it, a gap or hypocellular layer is mostly composed of GFAP+ cellular expansions (Layer II). Next to the gap layer, the astrocyte ribbon is represented (Layer III), continued by a transition zone to the brain parenchyma (Layer IV). (B) Electron microscopy coronal image of the human SVZ obtained from a 53-year-old female donor. Note the typical organization of this human neurogenic niche (Layers I to IV). b, astrocyte; e, ependymal cell; m, microglia. Scale bar: 4 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585225&req=5

Figure 4: Organization of the adult human SVZ. (A) Diagram representing the adult human SVZ. A monolayer of ependymal cells (Layer I) separates the lateral ventricle from the SVZ. Adjacent to it, a gap or hypocellular layer is mostly composed of GFAP+ cellular expansions (Layer II). Next to the gap layer, the astrocyte ribbon is represented (Layer III), continued by a transition zone to the brain parenchyma (Layer IV). (B) Electron microscopy coronal image of the human SVZ obtained from a 53-year-old female donor. Note the typical organization of this human neurogenic niche (Layers I to IV). b, astrocyte; e, ependymal cell; m, microglia. Scale bar: 4 μm.
Mentions: The organization of the adult human SVZ shows some divergences from the classical SVZ described for other mammalian species. In humans, the SVZ is composed by an ependymal layer (Layer I) that is in contact with the ventricular lumen. Next to this layer, there is a gap or hypocellular layer (Layer II), which is formed during postnatal development as a consequence of neuroblast depletion in this region. It is mostly populated by GFAP immunopositive cell expansions, although ependymal cells also send basal processes into this area. Adjacent to the hypocellular layer, there is a dense ribbon of cell bodies (Layer III) that contains astrocytes with a variable morphology, and is continued by a transition region (Layer IV) with few cells and similar to the underlying brain parenchyma (Figure 4). The human SVZ also acts as a NSCs niche capable of generating new neurons (Quinones-Hinojosa et al., 2006). During fetal and pediatric stages, SVZ-derived neuroblasts migrate via RMS into the OB (Sanai et al., 2004, 2011; van den Berge et al., 2010; Guerrero-Cazares et al., 2011). However, when the migration of neuroblasts to the OB was being studied in infants, it was unexpectedly found that there is another major migratory pathway of immature neurons destined for the prefrontal cortex (Sanai et al., 2011), suggesting that OB neurogenesis is less relevant in the human brain. In fact, the incorporation of new neurons into the human OB is nearly extinct by adulthood, as revealed by the measurement of 14C concentrations in the genomic DNA of these cells, which corresponded to the levels of atmospheric 14C at the time of birth of the examined individuals (Bergmann et al., 2012). Using the same birth dating approach, a recent study demonstrated that there is a postnatal cell turnover in the striatum of adult humans. This was corroborated by the incorporation of thymidine analog iododeoxyuridine (IdU) in striatal cells of cancer patients subjected to radiosensitization. Assessment of the expression of specific markers led these investigators to conclude that, new cells in the striatum correspond to neuronal and oligodendrocyte lineage cells (Ernst et al., 2014). Although authors suggested that these neurons likely derive from the SVZ, other origins cannot be excluded. In this regard, the production of new neurons in the adult human SVZ is still subject to debate. Most studies point to a dramatic decrease in DCX positive cells in the RMS and the OB from fetal to adult stages (Sanai et al., 2004; Wang et al., 2011). Moreover, other study demonstrated that most of the newly generated cells during adulthood correspond to non-neuronal cells, such as oligodendrocytes (Bergmann et al., 2012), suggesting that the oligodendrogenic process acquires more significance in the human brain.

Bottom Line: This review provides a compilation of the current knowledge about the age-related changes in the NSC population, as well as the fate of the newly generated cells in the aged brain.It is known that the neurogenic capacity is clearly disrupted during aging, while the production of oligodendroglial cells is not compromised.Interestingly, the human brain seems to primarily preserve the ability to produce new oligodendrocytes instead of neurons, which could be related to the development of neurological disorders.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Comparative Neurobiology, Department of Cell Biology, Instituto Cavanilles de Biodiversidad y Biología Evolutiva, University of Valencia, CIBERNED Valencia, Spain ; Department of Stem Cells, Andalusian Center for Molecular Biology and Regenerative Medicine Seville, Spain.

ABSTRACT
Neural stem cells (NSCs) persist in the adult mammalian brain through life. The subventricular zone (SVZ) is the largest source of stem cells in the nervous system, and continuously generates new neuronal and glial cells involved in brain regeneration. During aging, the germinal potential of the SVZ suffers a widespread decline, but the causes of this turn down are not fully understood. This review provides a compilation of the current knowledge about the age-related changes in the NSC population, as well as the fate of the newly generated cells in the aged brain. It is known that the neurogenic capacity is clearly disrupted during aging, while the production of oligodendroglial cells is not compromised. Interestingly, the human brain seems to primarily preserve the ability to produce new oligodendrocytes instead of neurons, which could be related to the development of neurological disorders. Further studies in this matter are required to improve our understanding and the current strategies for fighting neurological diseases associated with senescence.

No MeSH data available.


Related in: MedlinePlus