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Wnt Signaling in Neurogenesis during Aging and Physical Activity.

Chen M, Do H - Brain Sci (2012)

Bottom Line: Relatively little is known, however, about how aging and physical activity affect the Wnt signaling pathway.Herein, we briefly review the salient features of neurogenesis in young and then in old adult animals.Then, we discuss Wnt signaling and review the very few in vitro and in vivo studies that have examined the Wnt signaling pathways in aging and physical activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, California State University, 5151 State University Drive, Los Angeles, CA 90032, USA. mchen@calstatela.edu.

ABSTRACT
Over the past decade, much progress has been made regarding our understanding of neurogenesis in both young and old animals and where it occurs throughout the lifespan, although the growth of new neurons declines with increasing age. In addition, physical activity can reverse this age-dependent decline in neurogenesis. Highly correlated with this decline is the degree of inter and intracellular Wnt signaling, the molecular mechanisms of which have only recently started to be elucidated. So far, most of what we know about intracellular signaling during/following exercise centers around the CREB/CRE initiated transcriptional events. Relatively little is known, however, about how aging and physical activity affect the Wnt signaling pathway. Herein, we briefly review the salient features of neurogenesis in young and then in old adult animals. Then, we discuss Wnt signaling and review the very few in vitro and in vivo studies that have examined the Wnt signaling pathways in aging and physical activity.

No MeSH data available.


Related in: MedlinePlus

Exercise releases norepinephrine (NE), which binds its GPCR, β-adrenergic receptor (βAR), and then activates cAMP-dependent protein kinase A (PKA), which is only one of many kinases capable of phosphorylating the transcription factor, cAMP-response element binding protein (CREB). Activated CREB is then able to transcribe a wide array of pro-survival genes, one of which is BDNF. The neurotrophin is then packaged into vesicles and released to the extracellular space, where it dimerizes before binding to its receptor, TrkB, which also dimerizes upon ligand binding. TrkB dimerization results in the receptor cross-phosphorylating on opposite tyrosine residues, which then activates many different downstream intracellular signaling pro-survival pathways, only two of which are illustrated here: the phosphatidylinositol 3′-kinase (PI-3K) and mitogen-activated protein kinase (MAPK), ultimately also phosphorylating CREB for continued transcription of BDNF. Any of these pathways can be slowed down or inactivated by the action of phosphatases.
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brainsci-02-00745-f003: Exercise releases norepinephrine (NE), which binds its GPCR, β-adrenergic receptor (βAR), and then activates cAMP-dependent protein kinase A (PKA), which is only one of many kinases capable of phosphorylating the transcription factor, cAMP-response element binding protein (CREB). Activated CREB is then able to transcribe a wide array of pro-survival genes, one of which is BDNF. The neurotrophin is then packaged into vesicles and released to the extracellular space, where it dimerizes before binding to its receptor, TrkB, which also dimerizes upon ligand binding. TrkB dimerization results in the receptor cross-phosphorylating on opposite tyrosine residues, which then activates many different downstream intracellular signaling pro-survival pathways, only two of which are illustrated here: the phosphatidylinositol 3′-kinase (PI-3K) and mitogen-activated protein kinase (MAPK), ultimately also phosphorylating CREB for continued transcription of BDNF. Any of these pathways can be slowed down or inactivated by the action of phosphatases.

Mentions: Adult hippocampal neurogenesis enhances learning [89] and prevents cognitive decline [90] through an up-regulation of BDNF, which, upon binding to its receptor, TrkB [90], activates a wide array of intracellular signaling cell survival pathways (see [91] for review; [90], (Figure 3)). Likewise, exercise in young adults up-regulates various neurotrophins, particularly BDNF (and TrkB), in the hippocampus [87,91,92,93], eNOS and NO, leading to enhanced angiogenesis [94,95] or insulin-like growth factor I (IGF-1) from the periphery [96], thereby promoting neurogenesis [97,98]. As an epigenetic mechanism, such up-regulation may be mediated via suspension of the transcriptional repressing effects on transcription, specifically, for example, methyl CpG binding protein 2 (MeCp2), which is most commonly seen in sedentary rats (reviewed in [92]). As neurons depolarize McCp2 dissociates from the bdnf promotor IV region and then is phosphorylated as much as 25% in adult exercising rats [92].


Wnt Signaling in Neurogenesis during Aging and Physical Activity.

Chen M, Do H - Brain Sci (2012)

Exercise releases norepinephrine (NE), which binds its GPCR, β-adrenergic receptor (βAR), and then activates cAMP-dependent protein kinase A (PKA), which is only one of many kinases capable of phosphorylating the transcription factor, cAMP-response element binding protein (CREB). Activated CREB is then able to transcribe a wide array of pro-survival genes, one of which is BDNF. The neurotrophin is then packaged into vesicles and released to the extracellular space, where it dimerizes before binding to its receptor, TrkB, which also dimerizes upon ligand binding. TrkB dimerization results in the receptor cross-phosphorylating on opposite tyrosine residues, which then activates many different downstream intracellular signaling pro-survival pathways, only two of which are illustrated here: the phosphatidylinositol 3′-kinase (PI-3K) and mitogen-activated protein kinase (MAPK), ultimately also phosphorylating CREB for continued transcription of BDNF. Any of these pathways can be slowed down or inactivated by the action of phosphatases.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061808&req=5

brainsci-02-00745-f003: Exercise releases norepinephrine (NE), which binds its GPCR, β-adrenergic receptor (βAR), and then activates cAMP-dependent protein kinase A (PKA), which is only one of many kinases capable of phosphorylating the transcription factor, cAMP-response element binding protein (CREB). Activated CREB is then able to transcribe a wide array of pro-survival genes, one of which is BDNF. The neurotrophin is then packaged into vesicles and released to the extracellular space, where it dimerizes before binding to its receptor, TrkB, which also dimerizes upon ligand binding. TrkB dimerization results in the receptor cross-phosphorylating on opposite tyrosine residues, which then activates many different downstream intracellular signaling pro-survival pathways, only two of which are illustrated here: the phosphatidylinositol 3′-kinase (PI-3K) and mitogen-activated protein kinase (MAPK), ultimately also phosphorylating CREB for continued transcription of BDNF. Any of these pathways can be slowed down or inactivated by the action of phosphatases.
Mentions: Adult hippocampal neurogenesis enhances learning [89] and prevents cognitive decline [90] through an up-regulation of BDNF, which, upon binding to its receptor, TrkB [90], activates a wide array of intracellular signaling cell survival pathways (see [91] for review; [90], (Figure 3)). Likewise, exercise in young adults up-regulates various neurotrophins, particularly BDNF (and TrkB), in the hippocampus [87,91,92,93], eNOS and NO, leading to enhanced angiogenesis [94,95] or insulin-like growth factor I (IGF-1) from the periphery [96], thereby promoting neurogenesis [97,98]. As an epigenetic mechanism, such up-regulation may be mediated via suspension of the transcriptional repressing effects on transcription, specifically, for example, methyl CpG binding protein 2 (MeCp2), which is most commonly seen in sedentary rats (reviewed in [92]). As neurons depolarize McCp2 dissociates from the bdnf promotor IV region and then is phosphorylated as much as 25% in adult exercising rats [92].

Bottom Line: Relatively little is known, however, about how aging and physical activity affect the Wnt signaling pathway.Herein, we briefly review the salient features of neurogenesis in young and then in old adult animals.Then, we discuss Wnt signaling and review the very few in vitro and in vivo studies that have examined the Wnt signaling pathways in aging and physical activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, California State University, 5151 State University Drive, Los Angeles, CA 90032, USA. mchen@calstatela.edu.

ABSTRACT
Over the past decade, much progress has been made regarding our understanding of neurogenesis in both young and old animals and where it occurs throughout the lifespan, although the growth of new neurons declines with increasing age. In addition, physical activity can reverse this age-dependent decline in neurogenesis. Highly correlated with this decline is the degree of inter and intracellular Wnt signaling, the molecular mechanisms of which have only recently started to be elucidated. So far, most of what we know about intracellular signaling during/following exercise centers around the CREB/CRE initiated transcriptional events. Relatively little is known, however, about how aging and physical activity affect the Wnt signaling pathway. Herein, we briefly review the salient features of neurogenesis in young and then in old adult animals. Then, we discuss Wnt signaling and review the very few in vitro and in vivo studies that have examined the Wnt signaling pathways in aging and physical activity.

No MeSH data available.


Related in: MedlinePlus