Linked Life Data

20007481

Source:http://linkedlifedata.com/resource/pubmed/id/20007481

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pubmed-article:20007481pubmed:abstractTextRestraint stress produces changes in the sleep pattern that are mainly characterized by a delayed increase in rapid eye movement sleep (REMS) amounts. Because the serotonin (5-HT) and the hypocretin (hcrt) systems that regulate REMS are interconnected, we used mutant mice deficient in the 5-HT transporter (5-HTT(-/-)) to examine the role of 5-HT and hcrt neurotransmissions in the sleep response to stress. In contrast to wild-type mice, restraint stress did not induce a delayed increase in REMS amounts in 5-HTT(-/-) mice, indicating impaired sleep homeostasis in mutants. However, pharmacological blockade of the hcrt type 1 receptor (hcrt-R1) before restraint stress restored the REMS increase in 5-HTT(-/-) mice. In line with this finding, 5-HTT(-/-) mutants displayed after restraint stress higher long-lasting activation of hypothalamic preprohcrt neurons than wild-type mice and elevated levels of the hcrt-1 peptide and the hcrt-R1 mRNA in the anterior raphe area. Thus, hypocretinergic neurotransmission was enhanced by stress in 5-HTT(-/-) mice. Furthermore, in 5-HTT(-/-) but not wild-type mice, hypothalamic levels of the 5-HT metabolite 5-hydroxyindole acetic acid significantly increased after restraint stress, indicating a marked enhancement of serotonergic neurotransmission in mutants. Altogether, our data show that increased serotonergic -and in turn hypocretinergic- neurotransmissions exert an inhibitory influence on stress-induced delayed REMS. We propose that the direct interactions between hcrt neurons in the hypothalamus and 5-HT neurons in the anterior raphe nuclei account, at least in part, for the adaptive sleep-wakefulness regulations triggered by acute stress.lld:pubmed
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pubmed-article:20007481pubmed:articleTitleAltered sleep homeostasis after restraint stress in 5-HTT knock-out male mice: a role for hypocretins.lld:pubmed
pubmed-article:20007481pubmed:affiliationUniversité Pierre et Marie Curie-Paris 6, Faculté de Médecine Pierre et Marie Curie, Site Pitié-Salpêtrière, Institut Fédératif de Recherche 70 des Neurosciences, Unité Mixte de Recherche S677, F-75013 Paris, France.lld:pubmed
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