IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
artículos
Título:
Neurogenic niche modulation by activated microglia: transforming growth factor beta increases neurogenesis in the adult dentate gyrus
Autor/es:
BATTISTA, D; FERRARI, CC; GAGE, FH; PITOSSI, FJ
Revista:
EUROPEAN JOURNAL OF NEUROSCIENCE
Referencias:
Año: 2006 p. 83 - 93
ISSN:
0953-816X
Resumen:
Adult neural stem cells (NSC) proliferate and differentiate depending on the composition of the cellular and molecular niche in which
they are immersed. Until recently, microglial cells have been ignored as part of the neurogenic niche. We studied the dynamics of
NSC proliferation and differentiation in the dentate gyrus of the hippocampus (DG) and characterized the changes of the neurogenic
niche in adrenalectomized animals (ADX). At the cellular level, we found increased NSC proliferation and neurogenesis in the ADX
animals. In addition, a morphologically distinct subpopulation of NSC (Nestin+ GFAP) with increased proliferating profile was
detected. Interestingly, the number of microglial cells at stages 2 and 3 of activation correlated with increased neurogenesis
(r2 ¼ 0.999) and the number of Nestin-positive cells (r2 ¼ 0.96). At the molecular level, transforming growth factor beta (TGF-b)
mRNA levels were increased 10-fold in ADX animals. Interestingly, TGF-b levels correlated with the amount of neurogenesis
detected (r2 ¼ 0.99) and the number of stage 2 and 3 microglial cells (r2 ¼ 0.94). Furthermore, blockade of TGF-b biological activity
by administration of an anti-TGF-b type II receptor antibody diminished the percentage of 5-bromo-2¢-deoxyuridine (BrdU) PSANCAM-
positive cells in vivo. Moreover, TGF-b was able to promote neurogenesis in NSC primary cultures. This work supports the
idea that activated microglial cells are not pro- or anti-neurogenic per se, but the balance between pro- and anti-inflammatory
secreted molecules influences the final effect of this activation. Importantly, we identified an anti-inflammatory cytokine, TGF-b, with
neurogenic potential in the adult brain.GFAP) with increased proliferating profile was
detected. Interestingly, the number of microglial cells at stages 2 and 3 of activation correlated with increased neurogenesis
(r2 ¼ 0.999) and the number of Nestin-positive cells (r2 ¼ 0.96). At the molecular level, transforming growth factor beta (TGF-b)
mRNA levels were increased 10-fold in ADX animals. Interestingly, TGF-b levels correlated with the amount of neurogenesis
detected (r2 ¼ 0.99) and the number of stage 2 and 3 microglial cells (r2 ¼ 0.94). Furthermore, blockade of TGF-b biological activity
by administration of an anti-TGF-b type II receptor antibody diminished the percentage of 5-bromo-2¢-deoxyuridine (BrdU) PSANCAM-
positive cells in vivo. Moreover, TGF-b was able to promote neurogenesis in NSC primary cultures. This work supports the
idea that activated microglial cells are not pro- or anti-neurogenic per se, but the balance between pro- and anti-inflammatory
secreted molecules influences the final effect of this activation. Importantly, we identified an anti-inflammatory cytokine, TGF-b, with
neurogenic potential in the adult brain.r2 ¼ 0.999) and the number of Nestin-positive cells (r2 ¼ 0.96). At the molecular level, transforming growth factor beta (TGF-b)
mRNA levels were increased 10-fold in ADX animals. Interestingly, TGF-b levels correlated with the amount of neurogenesis
detected (r2 ¼ 0.99) and the number of stage 2 and 3 microglial cells (r2 ¼ 0.94). Furthermore, blockade of TGF-b biological activity
by administration of an anti-TGF-b type II receptor antibody diminished the percentage of 5-bromo-2¢-deoxyuridine (BrdU) PSANCAM-
positive cells in vivo. Moreover, TGF-b was able to promote neurogenesis in NSC primary cultures. This work supports the
idea that activated microglial cells are not pro- or anti-neurogenic per se, but the balance between pro- and anti-inflammatory
secreted molecules influences the final effect of this activation. Importantly, we identified an anti-inflammatory cytokine, TGF-b, with
neurogenic potential in the adult brain.b levels correlated with the amount of neurogenesis
detected (r2 ¼ 0.99) and the number of stage 2 and 3 microglial cells (r2 ¼ 0.94). Furthermore, blockade of TGF-b biological activity
by administration of an anti-TGF-b type II receptor antibody diminished the percentage of 5-bromo-2¢-deoxyuridine (BrdU) PSANCAM-
positive cells in vivo. Moreover, TGF-b was able to promote neurogenesis in NSC primary cultures. This work supports the
idea that activated microglial cells are not pro- or anti-neurogenic per se, but the balance between pro- and anti-inflammatory
secreted molecules influences the final effect of this activation. Importantly, we identified an anti-inflammatory cytokine, TGF-b, with
neurogenic potential in the adult brain.r2 ¼ 0.99) and the number of stage 2 and 3 microglial cells (r2 ¼ 0.94). Furthermore, blockade of TGF-b biological activity
by administration of an anti-TGF-b type II receptor antibody diminished the percentage of 5-bromo-2¢-deoxyuridine (BrdU) PSANCAM-
positive cells in vivo. Moreover, TGF-b was able to promote neurogenesis in NSC primary cultures. This work supports the
idea that activated microglial cells are not pro- or anti-neurogenic per se, but the balance between pro- and anti-inflammatory
secreted molecules influences the final effect of this activation. Importantly, we identified an anti-inflammatory cytokine, TGF-b, with
neurogenic potential in the adult brain.b type II receptor antibody diminished the percentage of 5-bromo-2¢-deoxyuridine (BrdU) PSANCAM-
positive cells in vivo. Moreover, TGF-b was able to promote neurogenesis in NSC primary cultures. This work supports the
idea that activated microglial cells are not pro- or anti-neurogenic per se, but the balance between pro- and anti-inflammatory
secreted molecules influences the final effect of this activation. Importantly, we identified an anti-inflammatory cytokine, TGF-b, with
neurogenic potential in the adult brain.in vivo. Moreover, TGF-b was able to promote neurogenesis in NSC primary cultures. This work supports the
idea that activated microglial cells are not pro- or anti-neurogenic per se, but the balance between pro- and anti-inflammatory
secreted molecules influences the final effect of this activation. Importantly, we identified an anti-inflammatory cytokine, TGF-b, with
neurogenic potential in the adult brain.per se, but the balance between pro- and anti-inflammatory
secreted molecules influences the final effect of this activation. Importantly, we identified an anti-inflammatory cytokine, TGF-b, with
neurogenic potential in the adult brain.b, with
neurogenic potential in the adult brain.