Interneuronal growth and expression of interneuronal markers in visual cortex of mice with transgenic activation of Ras

Patz, Silke; Colovic, Corinna; Wawro, Stefanie; Lafenêtre, Pauline; Leske, Oliver; Heumann, Rolf; Schönfelder, Sabine; Tomaschewski, Jana; Räk, Andrea; Wahle, Petra

doi:10.1007/s00221-008-1688-y

Cited by 2 publications

(3 citation statements)

References 61 publications

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“…N ‐methyl‐d‐aspartate receptor‐mediated glutamatergic neurotransmission inhibits neurogenesis (Cameron et al 1995; Maekawa et al 2009; Nacher & McEwen 2006; Petrus et al 2009), while GABAergic input modulates NMDA receptor‐mediated effects in a stage‐dependent manner (Ge et al 2007; Petrus et al 2009). Structural changes of GABAergic interneurons as a consequence of altered glutamatergic input (Alpár et al 2004; Patz et al 2009) suggest modified inhibitory systems, which in turn may mediate suppressive synRas effects.…”

Section: Discussionmentioning

confidence: 99%

Neuronal Ras activation inhibits adult hippocampal progenitor cell division and impairs spatial short‐term memory

Manns

Bichler

Leske

et al. 2010

Genes Brain and Behavior

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A large number of endogenous and exogenous factors have been identified to upregulate and downregulate proliferation, differentiation and/or survival of newborn cells in the adult hippocampus. For studying neuronal mechanisms mediating the impact of those factors, we used a transgenic synRas mouse model expressing constitutively activated Valin12-Harvey Ras selectively in differentiated neurons. BrdU injections showed significantly reduced proliferation of new cells within the adult hippocampus of transgenic animals compared with their wild-type siblings. In contrast, the relative survival of newborn cells was increased in synRas mice, although this effect did not fully compensate for diminished proliferation. Inhibition of progenitor cell proliferation and enhancement of cellular survival were more pronounced in males compared with females. Double labelling and doublecortin immunostaining verified that specifically newborn neurons were decreased in synRas mice. Reduced cell generation was observed already 2 h after BrdU pulse injections, identifying an early precursor cell population as target of the inhibitory transgene effect. Differences in proliferation remained stable after 24 h and were specific for the subgranular zone of the dentate gyrus, as subventricular cell generation was not affected supporting a non-cell autonomous effect on neural hippocampal progenitors. Transgene expression only starts with synaptic differentiation and therefore reduced proliferation must represent an indirect secondary consequence of synRas activity in differentiated neurons. This was associated with impaired spatial short-term memory capacities as observed in a radial maze paradigm. Our data suggest that constantly high Ras activity in differentiated neurons downregulates hippocampal precursor cell generation in the neuronal lineage, but is modulated by sex-dependent factors.

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Section: Discussionmentioning

confidence: 99%

Neuronal Ras activation inhibits adult hippocampal progenitor cell division and impairs spatial short‐term memory

Manns

Bichler

Leske

et al. 2010

Genes Brain and Behavior

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“… [1] Manns et al (2010), [2] Lafenêtre et al (2010), [3] Heumann et al (2000), [4] Arendt et al (2004), [5] Seeger et al (2005), [6] Gärtner et al (2005), [7] Gärtner et al (2004), [8] Patz et al (2009) .…”

Section: The Synras Mouse Modelmentioning

confidence: 99%

“…GABAergic interneurons show a different pattern of glutamate decarboxylase mRNA expression compared to wild type siblings though interneurons rarely express the H-Ras transgene (Heumann et al, 2000; Patz et al, 2009). Both, glutamate and GABA are well described neurotransmitters that are involved in the regulation of adult neurogenesis (e.g., Wang et al, 2005; Nacher and McEwan, 2006; Ge et al, 2007a).…”

Section: The Synras Mouse Modelmentioning

confidence: 99%

Role of Neuronal Ras Activity in Adult Hippocampal Neurogenesis and Cognition

Manns¹,

Leske²,

Gottfried³

et al. 2011

Front. Neurosci.

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Hippocampal neurogenesis in the adult mammalian brain is modulated by various signals like growth factors, hormones, neuropeptides, and neurotransmitters. All of these factors can (but not necessarily do) converge on the activation of the G protein Ras. We used a transgenic mouse model (synRas mice) expressing constitutively activated G12V-Harvey Ras selectively in differentiated neurons to investigate the possible effects onto neurogenesis. H-Ras activation in neurons attenuates hippocampal precursor cell generation at an early stage of the proliferative cascade before neuronal lineage determination occurs. Therefore it is unlikely that the transgenically activated H-Ras in neurons mediates this effect by a direct, intracellular signaling mechanism. Voluntary exercise restores neurogenesis up to wild type level presumably mediated by brain-derived neurotrophic factor. Reduced neurogenesis is linked to impairments in spatial short-term memory and object recognition, the latter can be rescued by voluntary exercise, as well. These data support the view that new cells significantly increase complexity that can be processed by the hippocampal network when experience requires high demands to associate stimuli over time and/or space.

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Interneuronal growth and expression of interneuronal markers in visual cortex of mice with transgenic activation of Ras

Cited by 2 publications

References 61 publications

Neuronal Ras activation inhibits adult hippocampal progenitor cell division and impairs spatial short‐term memory

Neuronal Ras activation inhibits adult hippocampal progenitor cell division and impairs spatial short‐term memory

Role of Neuronal Ras Activity in Adult Hippocampal Neurogenesis and Cognition

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