CREB in adult neurogenesis – master and partner in the development of adult‐born neurons?

Merz, Katharina; Herold, Sabine; Lie, Dieter Chichung

doi:10.1111/j.1460-9568.2011.07606.x

Cited by 150 publications

(141 citation statements)

References 104 publications

Supporting

Mentioning

133

Contrasting

Order By: Relevance

“…Shh enhances electrical activity in the developing spinal cord (28), leading to Ca 2+ influx and activation of several protein kinases, including PKA, which leads to phosphorylation and activation of CREB as shown in this study and others (39). In the adult brain where neural cells at different stages of maturation coexist, electrical activity and P-CREB are progressively up-regulated as newborn neurons differentiate (40). Similarly, we find that mutating potential binding sites for CREB in neural plate samples does not affect gli1 transcription, whereas in the spinal cord these mutations reveal a repressive character for these regulatory sites.…”

Section: Discussionmentioning

confidence: 90%

Inversion of Sonic hedgehog action on its canonical pathway by electrical activity

Belgacem

Borodinsky

2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Sonic hedgehog (Shh) is a morphogenic protein that operates through the Gli transcription factor-dependent canonical pathway to orchestrate normal development of many tissues. Because aberrant levels of Gli activity lead to a wide spectrum of diseases ranging from neurodevelopmental defects to cancer, understanding the regulatory mechanisms of Shh canonical pathway is paramount. During early stages of spinal cord development, Shh specifies neural progenitors through the canonical signaling. Despite persistence of Shh as spinal cord development progresses, Gli activity is switched off by unknown mechanisms. In this study we find that Shh inverts its action on Gli during development. Strikingly, Shh decreases Gli signaling in the embryonic spinal cord by an electrical activity- and cAMP-dependent protein kinase-mediated pathway. The inhibition of Gli activity by Shh operates at multiple levels. Shh promotes cytosolic over nuclear localization of Gli2, induces Gli2 and Gli3 processing into repressor forms, and activates cAMP-responsive element binding protein that in turn represses gli1 transcription. The regulatory mechanisms identified in this study likely operate with different spatiotemporal resolution and ensure effective down-regulation of the canonical Shh signaling as spinal cord development progresses. The developmentally regulated intercalation of electrical activity in the Shh pathway may represent a paradigm for switching from canonical to noncanonical roles of developmental cues during neuronal differentiation and maturation.

show abstract

Section: Discussionmentioning

confidence: 90%

Inversion of Sonic hedgehog action on its canonical pathway by electrical activity

Belgacem

Borodinsky

2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Previous work has detected robust pCREB expression in the SGZ, which has been localized to adult-born immature neuronal cell populations (Merz et al 2011). Interestingly, WT mice exhibited a much greater level of CREB phosphorylation in the SGZ than MSK1 2/2 mice (Fig.…”

Section: Experience-induced Proliferationmentioning

confidence: 86%

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

et al. 2012

View full text Add to dashboard Cite

Environmental enrichment (EE) has marked beneficial effects on cognitive capacity. Given the possibility that this form of neuronal plasticity could function via the actuation of the same cellular signaling pathways that underlie learning/memory formation, we examined whether the MAPK cascade effector, mitogen/stress-activated kinase 1 (MSK1), could play a role in this process. MSK1 functions as a key signaling intermediate that couples changes in neuronal activity into inducible gene expression, neuronal plasticity, and learning/memory. Here, we show that MSK1 is expressed in excitatory cell layers of the hippocampus, progenitor cells of the subgranular zone (SGZ), and adult-born immature neurons. MSK1 2/2 mice exhibit reduced spinogenesis and decreased dendritic branching complexity in hippocampal neurons, compared with WT mice. Further, in MSK1 2/2 mice, progenitor cell proliferation within the SGZ was significantly reduced and, correspondingly, the number of immature neurons within the dentate gyrus was significantly reduced. Consistent with prior work, MSK1 2/2 mice displayed deficits in both spatial and recognition memory tasks. Strikingly, cognitive enhancement resulting from a 40-d period of EE was markedly reduced in MSK1 2/2 animals. MSK1 2/2 mice exhibited reduced levels of EE-induced spinogenesis and SGZ progenitor proliferation. Taken together, these data reveal that MSK1 serves as a critical regulator of hippocampal physiology and function and that MSK1 serves as a key conduit by which enriching stimuli augment cellular plasticity and cognition.

show abstract

“…Because activated/phosphorylated cAMP-response element binding protein (pCREB) is known to be associated with Bdnf and Ntf3 and is important for learning and memory (24)(25)(26)(27), the level of pCREB was also determined. A significant reduction in pCREB was observed in irradiated WT mice (80% reduction, t = 2.62, P < 0.05), implying a diminished level of pCREB-mediated neuronal function in this cohort.…”

Section: Ec-sod and Irradiation Affect Expression Of Neurotrophic Facmentioning

confidence: 99%

Extracellular superoxide dismutase is important for hippocampal neurogenesis and preservation of cognitive functions after irradiation

Zou¹,

Corniola²,

Leu

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Cranial irradiation is widely used in cancer therapy, but it often causes cognitive defects in cancer survivors. Oxidative stress is considered a major cause of tissue injury from irradiation. However, in an earlier study mice deficient in the antioxidant enzyme extracellular superoxide dismutase (EC-SOD KO) showed reduced sensitivity to radiation-induced defects in hippocampal functions. To further dissect the role of EC-SOD in neurogenesis and in response to irradiation, we generated a bigenic EC-SOD mouse model (OE mice) that expressed high levels of EC-SOD in mature neurons in an otherwise EC-SOD-deficient environment. EC-SOD deficiency was associated with reduced progenitor cell proliferation in the subgranular zone of dentate gyrus in KO and OE mice. However, high levels of EC-SOD in the granule cell layer supported normal maturation of newborn neurons in OE mice. Following irradiation, wild-type mice showed reduced hippocampal neurogenesis, reduced dendritic spine densities, and defects in cognitive functions. OE and KO mice, on the other hand, were largely unaffected, and the mice performed normally in neurocognitive tests. Although the resulting hippocampalrelated functions were similar in OE and KO mice following cranial irradiation, molecular analyses suggested that they may be governed by different mechanisms: whereas neurotrophic factors may influence radiation responses in OE mice, dendritic maintenance may be important in the KO environment. Taken together, our data suggest that EC-SOD plays an important role in all stages of hippocampal neurogenesis and its associated cognitive functions, and that highlevel EC-SOD may provide protection against irradiation-related defects in hippocampal functions.

show abstract

CREB in adult neurogenesis – master and partner in the development of adult‐born neurons?

Cited by 150 publications

References 104 publications

Inversion of Sonic hedgehog action on its canonical pathway by electrical activity

Inversion of Sonic hedgehog action on its canonical pathway by electrical activity

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

Extracellular superoxide dismutase is important for hippocampal neurogenesis and preservation of cognitive functions after irradiation

Contact Info

Product

Resources

About