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REM Sleep Deprivation Reverses Neurochemical and Other Depressive-Like Alterations Induced by Olfactory Bulbectomy

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Abstract

There is compelling evidence that sleep deprivation (SD) is an effective strategy in promoting antidepressant effects in humans, whereas few studies were performed in relevant animal models of depression. Acute administration of antidepressants in humans and rats generates a quite similar effect, i.e., suppression of rapid eye movement (REM) sleep. Then, we decided to investigate the neurochemical alterations generated by a protocol of rapid eye movement sleep deprivation (REMSD) in the notably known animal model of depression induced by the bilateral olfactory bulbectomy (OBX). REMSD triggered antidepressant mechanisms such as the increment of brain-derived neurotrophic factor (BDNF) levels, within the substantia nigra pars compacta (SNpc), which were strongly correlated to the swimming time (r = 0.83; P < 0.0001) and hippocampal serotonin (5-HT) content (r = 0.66; P = 0.004). Moreover, there was a strong correlation between swimming time and hippocampal 5-HT levels (r = 0.70; P = 0.003), strengthen the notion of an antidepressant effect associated to REMSD in the OBX rats. In addition, REMSD robustly attenuated the hippocampal 5-HT deficiency produced by the OBX procedure. Regarding the rebound (REB) period, we observed the occurrence of a sustained antidepressant effect, indicated mainly by the swimming and climbing times which could be explained by the maintenance of the increased nigral BDNF expression. Hence, hippocampal 5-HT levels remained enhanced in the OBX group after this period. We suggested that the neurochemical complexity inflicted by the OBX model, counteracted by REMSD, is directly correlated to the nigral BDNF expression and hippocampal 5-HT levels. The present findings provide new information regarding the antidepressant mechanisms triggered by REMSD.

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Acknowledgements

This paper was supported by CAPES and the Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq—Brasil Grants Casadinho/Procad no. 552226/2011-4 and Universal no. 473861/2012-7 to MMSL. MMSL, SMZ, and CDC are recipients of CNPq fellowship. The authors wish to express their sincere gratitude to Prof. Dr. Roberto Andreatini from Pharmacology Department of UFPR for the technical assistance.

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The authors have declared that no conflict of interests exists.

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Authors and Affiliations

  1. Laboratório de Neurofisiologia, Departamento de Fisiologia, Universidade Federal do Paraná, Curitiba, PR, Brazil

    Maira J. Maturana, Cláudia Pudell, Adriano D. S. Targa, Laís S. Rodrigues, Ana Carolina D. Noseda, Mariana H. Fortes, Patrícia dos Santos, Anete C. Ferraz & Marcelo M. S. Lima

  2. Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil

    Cláudio Da Cunha

  3. Laboratório de Neurobiologia, Departamento de Patologia Básica, Universidade Federal do Paraná, Curitiba, PR, Brazil

    Sílvio M. Zanata

  4. Setor de Ciências Biológicas, Departamento de Fisiologia, Universidade Federal do Paraná, Av. Francisco H. dos Santos s/n, ZIP: 81.531-990, Caixa Postal: 19031, Curitiba, Paraná, Brazil

    Marcelo M. S. Lima

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  1. Maira J. Maturana
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Maturana, M.J., Pudell, C., Targa, A.D.S. et al. REM Sleep Deprivation Reverses Neurochemical and Other Depressive-Like Alterations Induced by Olfactory Bulbectomy. Mol Neurobiol 51, 349–360 (2015). https://doi.org/10.1007/s12035-014-8721-x

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