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Unpredictable Chronic Stress Alters Adenosine Metabolism in Zebrafish Brain

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Abstract

Stress is considered a risk factor for several human disorders. Despite the broad knowledge of stress responses in mammals, data on the relationship between unpredictable chronic stress (UCS) and its effects on purinergic signaling are limited. ATP hydrolysis by ectonucleotidases is an important source of adenosine, and adenosine deaminase (ADA) contributes to the control of the nucleoside concentrations. Considering that some stress models could affect signaling systems, the objective of this study was to investigate whether UCS alters ectonucleotidase and ADA pathway in zebrafish brain. Additionally, we analyzed ATP metabolism as well as ada1, ada2.1, ada2.2, adaL, and adaasi gene expression in zebrafish brain. Our results have demonstrated that UCS did not alter ectonucleotidase and soluble ADA activities. However, ecto-ADA activity was significantly decreased (26.8 %) in brain membranes of animals exposed to UCS when compared to the control group. Quantitative reverse transcription PCR (RT-PCR) analysis did not show significant changes on ADA gene expression after the UCS exposure. The brain ATP metabolism showed a marked increase in adenosine levels (ADO) in animals exposed to UCS. These data suggest an increase on extracellular adenosine levels in zebrafish brain. Since this nucleoside has neuromodulatory and anxiolytic effects, changes in adenosine levels could play a role in counteracting the stress, which could be related to a compensatory mechanism in order to restore the homeostasis.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

ARS:

Acute restraint stress

CRF:

Corticotropin-releasing hormone

HPI:

Hypothalamic–pituitary–interrenal axis

UCS:

Unpredictable chronic stress

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Acknowledgments

This study was supported by DECIT/SCTIE-MS through Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS; Proc. 10/0036-5, conv. n. 700545/2008 – PRONEX) and by FINEP research grant “Implantação, Modernização e Qualificação de Estrutura de Pesquisa da PUCRS” (PUCRSINFRA) # 01.11.0014-00. F.F.Z. was recipient of fellowship from CAPES. G.P.G. and L.W.K. were recipients of fellowships from the CNPQ/PNPD and CAPES/PNPD Program, respectively. C.D.B and M.R.B are Research Career Awardees of the CNPq.

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Laboratório de Neuroquímica e Psicofarmacologia, Programa de Pós-Graduação em Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Porto Alegre, RS, 90619-900, Brazil

    F. F. Zimmermann, S. Altenhofen, G. P. Cognato & C. D. Bonan

  2. Laboratório de Biologia Genômica e Molecular, Programa de Pós-Graduação em Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Porto Alegre, RS, 90619-900, Brazil

    L. W. Kist & M. R. Bogo

  3. Instituto de Toxicologia e Farmacologia, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Porto Alegre, 90619-900, Brazil

    C. E. Leite

  4. Laboratório de Neuroquímica Comportamental, Programa de Pós-Graduação em Bioquímica e Bioprospecção, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, RS, Brazil

    G. P. Cognato

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  1. F. F. Zimmermann
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  2. S. Altenhofen
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  3. L. W. Kist
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  4. C. E. Leite
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  7. C. D. Bonan
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Correspondence to C. D. Bonan.

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Zimmermann, F.F., Altenhofen, S., Kist, L.W. et al. Unpredictable Chronic Stress Alters Adenosine Metabolism in Zebrafish Brain. Mol Neurobiol 53, 2518–2528 (2016). https://doi.org/10.1007/s12035-015-9270-7

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