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2009 | 69 | 3 |
Tytuł artykułu

Antidepressant-like features of mice with transgenic activation of Ras in brain neurons

Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
Brain-derived neurotrophic factor (BDNF) is implicated in clinical depression. Thus, BDNF expression is enhanced by antidepressants while stress exposure and depression decreases it. A major BDNF intracellular signalling pathway is the Rasextracellular signal-regulated kinase (ERK) cascade. Here, we test its possible contribution on antidepressant activity by utilizing a synRas transgenic mouse model expressing constitutively activated human Ha-Ras in differentiated neurons [Heumann et al. (2000) J Cell Biol 151: 1537]. Immunoblotting analysis in hippocampus and cortex revealed that chronic fl uoxetine administration to C57Bl/6 mice led to an increased activation of endogenous Ras and activating ERK1/2 phosphorylation. SynRas mice exhibited chronically increased levels of activated Ras and activating ERK1/2 phosphorylation in the cortex and hippocampus. This was clearly associated with an antidepressant-like behaviour in four different animal models of depression. Furthermore, restraint stress-induced corticosterone response was attenuated in synRas mice, throughout stress and recovery time period. Because adult neurogenesis may play a role in depression we assessed the proliferation of hippocampal progenitors. Here we show that proliferation was not correlated with the antidepressant activity in synRas mice. Taken together, an antidepressant state was established in a genetic model of enhanced neuronal Ras signalling without correlation to hippocampal precursor cell proliferation.
Słowa kluczowe
Wydawca
-
Rocznik
Tom
69
Numer
3
Opis fizyczny
p.297
Twórcy
autor
  • Department of Molecular Neurobiochemistry, Ruhr University Bochum, Germany
autor
  • Prous Institute for Biomedical Research, Barcelona, Spain
autor
  • Department of Molecular Neurobiochemistry, Ruhr University Bochum, Germany
Bibliografia
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.agro-3ddb7cc6-b55d-426c-ab2f-19be84b9eaae
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