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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

Schematic representation of the subventricular zone (SVZ) and rostral migratory stream (RMS) in the young and aged rodent brain. (A) In the young brain, ependymal cells with cubical morphology integrate the barrier that separates the SVZ neurogenic cells from the lateral ventricle. Neuroblasts form large chains ensheathed by gliotubes of astrocytes. Thus, neuroblasts migrate through these migratory structures, which emerge from the SVZ and coalesce into the RMS that ends in the olfactory bulb (OB). (B) During aging, ependymal cells are flattened and their cilia scatter. Both ependymal cells and astrocytes accumulate dense bodies and intermediate filaments in their cytoplasm. There is a decrease in the number of neural stem cells (NSCs) identified as astrocytes contacting the ventricle, intermediate progenitor cells, and neuroblasts. As a result, the RMS tends to disappear in the aged brain.
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Figure 1: Schematic representation of the subventricular zone (SVZ) and rostral migratory stream (RMS) in the young and aged rodent brain. (A) In the young brain, ependymal cells with cubical morphology integrate the barrier that separates the SVZ neurogenic cells from the lateral ventricle. Neuroblasts form large chains ensheathed by gliotubes of astrocytes. Thus, neuroblasts migrate through these migratory structures, which emerge from the SVZ and coalesce into the RMS that ends in the olfactory bulb (OB). (B) During aging, ependymal cells are flattened and their cilia scatter. Both ependymal cells and astrocytes accumulate dense bodies and intermediate filaments in their cytoplasm. There is a decrease in the number of neural stem cells (NSCs) identified as astrocytes contacting the ventricle, intermediate progenitor cells, and neuroblasts. As a result, the RMS tends to disappear in the aged brain.

Mentions: The SVZ is the main neurogenic niche in the adult mammalian brain. It is known that NSCs within the SVZ derive from embryonic radial glia cells (Merkle et al., 2004; Kriegstein and Alvarez-Buylla, 2009; Morrens et al., 2012; Fuentealba et al., 2015). During the final stages of development, radial glia cells retract their apical processes but preserve the ventricle contact, turning into the ependymal cells and NSCs of the future SVZ (Merkle et al., 2004; Spassky et al., 2005). In the adult brain, ependymal cells constitute the postmitotic population of cells within the SVZ (Spassky et al., 2005). They are cubical cells containing lipid droplets in their cytoplasm and displaying cilia and microvilli in their apical surface. Ependymal cells form interdigitations, tight junctions and adherens junctions with each other to separate the SVZ from the cerebrospinal fluid of the ventricle cavity. On the other hand, NSCs are identified as a subpopulation of astrocytes called B1 astrocytes that differ from another subpopulation of non-neurogenic astrocytes (B2 astrocytes) (Doetsch et al., 1997, 1999a; Han et al., 2008; Ihrie and Alvarez-Buylla, 2008; Mirzadeh et al., 2008; Gil-Perotin et al., 2009; Morrens et al., 2012). Briefly, astrocytes present bundles of intermediate filaments and light cytoplasm. B1 astrocytes are located next to the ependymal layer, displaying chromatin clumps close to the nuclear membrane, and a primary cilium in the apical surface that extends into the ventricle cavity. In contrast, B2 astrocytes do not contact the ventricle. B1 astrocytes proliferate and give rise to intermediate progenitor cells (type C cells), which have very large, irregular nuclei with frequent invaginations and many mitochondria in their cytoplasm. Subsequently, intermediate progenitor cells differentiate into neuroblasts (type A cells), which are small, elongated cells with a reduced dark cytoplasm, containing numerous ribosomes and microtubules (Doetsch et al., 1997, 1999a; Peretto et al., 1999; Ponti et al., 2013). Neuroblasts form large chains ensheathed by gliotubes of astrocytes that emerge from the SVZ to coalesce into the rostral migratory stream (RMS) (Lois et al., 1996; Peretto et al., 1997; Alvarez-Buylla and Garcia-Verdugo, 2002) (Figure 1A). Through the gliotubes, neuroblasts migrate tangentially long distance before they reach their final destination, the olfactory bulb (OB). Then, neuroblasts move radially and mature into interneurons that integrate in preexisting functional circuits (Lois and Alvarez-Buylla, 1994; Lois et al., 1996; Luskin et al., 1997; Carleton et al., 2003; Alvarez-Buylla and Lim, 2004; Imayoshi et al., 2008; Kelsch et al., 2010; Lazarini and Lledo, 2011). In rodents, most SVZ precursor cells become neuroblasts to support OB neurogenesis, while a small subpopulation of new cells migrates to periventricular areas such as the corpus callosum or striatum, where they give rise to myelinating oligodendrocytes, both in the normal brain and after demyelinating lesion (Nait-Oumesmar et al., 1999; Menn et al., 2006; Gonzalez-Perez et al., 2009; Capilla-Gonzalez et al., 2014b).


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)

Schematic representation of the subventricular zone (SVZ) and rostral migratory stream (RMS) in the young and aged rodent brain. (A) In the young brain, ependymal cells with cubical morphology integrate the barrier that separates the SVZ neurogenic cells from the lateral ventricle. Neuroblasts form large chains ensheathed by gliotubes of astrocytes. Thus, neuroblasts migrate through these migratory structures, which emerge from the SVZ and coalesce into the RMS that ends in the olfactory bulb (OB). (B) During aging, ependymal cells are flattened and their cilia scatter. Both ependymal cells and astrocytes accumulate dense bodies and intermediate filaments in their cytoplasm. There is a decrease in the number of neural stem cells (NSCs) identified as astrocytes contacting the ventricle, intermediate progenitor cells, and neuroblasts. As a result, the RMS tends to disappear in the aged brain.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Schematic representation of the subventricular zone (SVZ) and rostral migratory stream (RMS) in the young and aged rodent brain. (A) In the young brain, ependymal cells with cubical morphology integrate the barrier that separates the SVZ neurogenic cells from the lateral ventricle. Neuroblasts form large chains ensheathed by gliotubes of astrocytes. Thus, neuroblasts migrate through these migratory structures, which emerge from the SVZ and coalesce into the RMS that ends in the olfactory bulb (OB). (B) During aging, ependymal cells are flattened and their cilia scatter. Both ependymal cells and astrocytes accumulate dense bodies and intermediate filaments in their cytoplasm. There is a decrease in the number of neural stem cells (NSCs) identified as astrocytes contacting the ventricle, intermediate progenitor cells, and neuroblasts. As a result, the RMS tends to disappear in the aged brain.
Mentions: The SVZ is the main neurogenic niche in the adult mammalian brain. It is known that NSCs within the SVZ derive from embryonic radial glia cells (Merkle et al., 2004; Kriegstein and Alvarez-Buylla, 2009; Morrens et al., 2012; Fuentealba et al., 2015). During the final stages of development, radial glia cells retract their apical processes but preserve the ventricle contact, turning into the ependymal cells and NSCs of the future SVZ (Merkle et al., 2004; Spassky et al., 2005). In the adult brain, ependymal cells constitute the postmitotic population of cells within the SVZ (Spassky et al., 2005). They are cubical cells containing lipid droplets in their cytoplasm and displaying cilia and microvilli in their apical surface. Ependymal cells form interdigitations, tight junctions and adherens junctions with each other to separate the SVZ from the cerebrospinal fluid of the ventricle cavity. On the other hand, NSCs are identified as a subpopulation of astrocytes called B1 astrocytes that differ from another subpopulation of non-neurogenic astrocytes (B2 astrocytes) (Doetsch et al., 1997, 1999a; Han et al., 2008; Ihrie and Alvarez-Buylla, 2008; Mirzadeh et al., 2008; Gil-Perotin et al., 2009; Morrens et al., 2012). Briefly, astrocytes present bundles of intermediate filaments and light cytoplasm. B1 astrocytes are located next to the ependymal layer, displaying chromatin clumps close to the nuclear membrane, and a primary cilium in the apical surface that extends into the ventricle cavity. In contrast, B2 astrocytes do not contact the ventricle. B1 astrocytes proliferate and give rise to intermediate progenitor cells (type C cells), which have very large, irregular nuclei with frequent invaginations and many mitochondria in their cytoplasm. Subsequently, intermediate progenitor cells differentiate into neuroblasts (type A cells), which are small, elongated cells with a reduced dark cytoplasm, containing numerous ribosomes and microtubules (Doetsch et al., 1997, 1999a; Peretto et al., 1999; Ponti et al., 2013). Neuroblasts form large chains ensheathed by gliotubes of astrocytes that emerge from the SVZ to coalesce into the rostral migratory stream (RMS) (Lois et al., 1996; Peretto et al., 1997; Alvarez-Buylla and Garcia-Verdugo, 2002) (Figure 1A). Through the gliotubes, neuroblasts migrate tangentially long distance before they reach their final destination, the olfactory bulb (OB). Then, neuroblasts move radially and mature into interneurons that integrate in preexisting functional circuits (Lois and Alvarez-Buylla, 1994; Lois et al., 1996; Luskin et al., 1997; Carleton et al., 2003; Alvarez-Buylla and Lim, 2004; Imayoshi et al., 2008; Kelsch et al., 2010; Lazarini and Lledo, 2011). In rodents, most SVZ precursor cells become neuroblasts to support OB neurogenesis, while a small subpopulation of new cells migrates to periventricular areas such as the corpus callosum or striatum, where they give rise to myelinating oligodendrocytes, both in the normal brain and after demyelinating lesion (Nait-Oumesmar et al., 1999; Menn et al., 2006; Gonzalez-Perez et al., 2009; Capilla-Gonzalez et al., 2014b).

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