References of "Puschel, Andreas W"
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See detailRegrowing the adult brain: NF-kappaB controls functional circuit formation and tissue homeostasis in the dentate gyrus.
Imielski, Yvonne; Schwamborn, Jens Christian UL; Luningschror, Patrick et al

in PLoS ONE (2012), 7(2), 30838

Cognitive decline during aging is correlated with a continuous loss of cells within the brain and especially within the hippocampus, which could be regenerated by adult neurogenesis. Here we show that ... [more ▼]

Cognitive decline during aging is correlated with a continuous loss of cells within the brain and especially within the hippocampus, which could be regenerated by adult neurogenesis. Here we show that genetic ablation of NF-kappaB resulted in severe defects in the neurogenic region (dentate gyrus) of the hippocampus. Despite increased stem cell proliferation, axogenesis, synaptogenesis and neuroprotection were hampered, leading to disruption of the mossy fiber pathway and to atrophy of the dentate gyrus during aging. Here, NF-kappaB controls the transcription of FOXO1 and PKA, regulating axogenesis. Structural defects culminated in behavioral impairments in pattern separation. Re-activation of NF-kappaB resulted in integration of newborn neurons, finally to regeneration of the dentate gyrus, accompanied by a complete recovery of structural and behavioral defects. These data identify NF-kappaB as a crucial regulator of dentate gyrus tissue homeostasis suggesting NF-kappaB to be a therapeutic target for treating cognitive and mood disorders. [less ▲]

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See detailThe stimulation of dendrite growth by Sema3A requires integrin engagement and focal adhesion kinase.
Schlomann, Uwe; Schwamborn, Jens Christian UL; Muller, Myriam et al

in Journal of Cell Science (2009), 122(Pt 12), 2034-42

The rate and direction of axon and dendrite growth depend on multiple guidance signals and growth factors. Semaphorin 3A (Sema3A) acts as a repellent for axons and attractant for dendrites. Here, we show ... [more ▼]

The rate and direction of axon and dendrite growth depend on multiple guidance signals and growth factors. Semaphorin 3A (Sema3A) acts as a repellent for axons and attractant for dendrites. Here, we show that the requirement for integrin engagement distinguishes the response of axons and dendrites to Sema3A in hippocampal neurons. Sema3A promotes the extension of hippocampal dendrites by a pathway that requires focal adhesion kinase (FAK). The stimulation of dendrite growth and FAK phosphorylation by Sema3A depend on integrin engagement. Unlike their function as a target of Sema3A during the collapse of axonal growth cones, integrins facilitate the stimulation of dendrite extension. Conditional inactivation of the genes encoding beta1 integrin or FAK blocks the growth-promoting effect of Sema3A but not the collapse of axonal growth cones. Our results demonstrate that different pathways mediate the stimulation of dendrite growth and the collapse of axonal growth cones by Sema3A. [less ▲]

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See detailGTPases and the control of neuronal polarity.
Schwamborn, Jens Christian UL; Li, Yinghua; Puschel, Andreas W.

in Methods in Enzymology (2006), 406

Neurons are probably the most highly polarized cell type and typically develop a single axon and several dendrites. The establishment of a polarized morphology and the functional specialization of axonal ... [more ▼]

Neurons are probably the most highly polarized cell type and typically develop a single axon and several dendrites. The establishment of a polarized morphology and the functional specialization of axonal and dendritic compartments are essential steps in the differentiation of neurons. Primary cultures of dissociated hippocampal neurons are a widely used system to study the development of neuronal differentiation. In this article, we will describe gain-of-function and loss-of-function approaches that allow us to analyze the role of GTPases in neuronal differentiation. [less ▲]

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See detailThe sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity.
Schwamborn, Jens Christian UL; Puschel, Andreas W.

in Nature Neuroscience (2004), 7(9), 923-9

The establishment of a polarized morphology is an essential step in the differentiation of neurons with a single axon and multiple dendrites. In cultured rat hippocampal neurons, one of several initially ... [more ▼]

The establishment of a polarized morphology is an essential step in the differentiation of neurons with a single axon and multiple dendrites. In cultured rat hippocampal neurons, one of several initially indistinguishable neurites is selected to become the axon. Both phosphatidylinositol 3,4,5-trisphosphate and the evolutionarily conserved Par complex (comprising Par3, Par6 and an atypical PKC (aPKC) such as PKClambda or PKCzeta) are involved in axon specification. However, the initial signals that establish cellular asymmetry and the pathways that subsequently translate it into structural changes remain to be elucidated. Here we show that localization of the GTPase Rap1B to the tip of a single neurite is a decisive step in determining which neurite becomes the axon. Using GTPase mutants and RNA interference, we found that Rap1B is necessary and sufficient to initiate the development of axons upstream of Cdc42 and the Par complex. [less ▲]

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See detailSemaphorin 3A stimulates neurite extension and regulates gene expression in PC12 cells.
Schwamborn, Jens Christian UL; Fiore, Roberto; Bagnard, Dominique et al

in Journal of Biological Chemistry (2004), 279(30), 30923-6

The secreted semaphorin 3A (Sema3A) is a member of a large family of proteins that act as guidance signals for axons and dendrites. While the receptors and signaling pathways that mediate the repulsive ... [more ▼]

The secreted semaphorin 3A (Sema3A) is a member of a large family of proteins that act as guidance signals for axons and dendrites. While the receptors and signaling pathways that mediate the repulsive effects of semaphorins are beginning to be understood in some detail, the mechanisms that are responsible for the ability of Sema3A to stimulate the extension of dendrites remain to be elucidated. Here we show that PC12 cells, a model widely used to study neuronal differentiation, can be used to dissect this pathway. Sema3A is as effective as nerve growth factor in stimulating the extension of neurites from PC12 cells. We show that Sema3A is able to regulate gene expression and identify mitochondria as a novel target of Sema3A signaling. Pharmacological block of mitochondrial reactive oxygen species production abolishes the extension of neurites in response to Sema3A. These results show that the characterization of transcripts that are regulated by axon guidance signals may help to identify novel components of their signaling pathways. [less ▲]

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