Artículo

Gonzalez, C.R.; Gonzalez, B.; Matzkin, M.E.; Muniz, J.A.; Cadet, J.L.; Garcia-Rill, E.; Urbano, F.J.; Vitullo, A.D.; Bisagno, V. "Psychostimulant-induced testicular toxicity in mice: Evidence of cocaine and caffeine effects on the local dopaminergic system" (2015) PLoS ONE. 10(11)
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Abstract:

Several organ systems can be affected by psychostimulant toxicity. However, there is not sufficient evidence about the impact of psychostimulant intake on testicular physiology and catecholaminergic systems. The aim of the present study was to further explore potential toxic consequences of chronic exposure to cocaine, caffeine, and their combination on testicular physiology. Mice were injected with a 13-day chronic binge regimen of caffeine (3x5mg/kg), cocaine (3×10mg/kg), or combined administration. Mice treated with cocaine alone or combined with caffeine showed reduced volume of the seminiferous tubule associated to a reduction in the number of spermatogonia. Cocaine-only and combined treatments induced increased lipid peroxidation evaluated by TBARS assay and decreased glutathione peroxidase mRNA expression. Importantly, caffeine-cocaine combination potentiated the cocaine-induced germ cell loss, and induced pro-apoptotic BAX protein expression and diminished adenosine receptor A1 mRNA levels. We analyzed markers of dopaminergic function in the testis and detected the presence of tyrosine hydroxylase (TH) in the cytoplasm of androgen-producing Leydig cells, but also in meiotic germs cells within seminiferous tubules. Moreover, using transgenic BAC-Drd1a-tdTomato and D2R-eGFP mice, we report for the first time the presence of dopamine receptors (DRs) D1 and D2 in testicular mouse Leydig cells. Interestingly, the presence of DRD1 was also detected in the spermatogonia nearest the basal lamina of the seminiferous tubules, which did not show TH staining. We observed that psychostimulants induced downregulation of DRs mRNA expression and upregulation of TH protein expression in the testis. These findings suggest a potential role of the local dopaminergic system in psychostimulant-induced testicular pathology.

Registro:

Documento: Artículo
Título:Psychostimulant-induced testicular toxicity in mice: Evidence of cocaine and caffeine effects on the local dopaminergic system
Autor:Gonzalez, C.R.; Gonzalez, B.; Matzkin, M.E.; Muniz, J.A.; Cadet, J.L.; Garcia-Rill, E.; Urbano, F.J.; Vitullo, A.D.; Bisagno, V.
Filiación:Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y Diagnóstico (CEBBAD), Universidad Maimónides, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Instituto de Investigaciones Farmacológicas, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Instituto de Biología y Medicina Experimental, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
NIDA Intramural Program, Molecular Neuropsychiatry Research Branch, Baltimore, MD, United States
Center for Translational Neuroscience, Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States
Laboratorio de Fisiología y Biología Molecular, Instituto de Fisiología, Biología Molecular y Neurociencias, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Palabras clave:adenosine A1 receptor; caffeine; catalase; cocaine; copper zinc superoxide dismutase; cycline; dopamine 1 receptor; dopamine 2 receptor; follitropin receptor; glutathione peroxidase; luteinizing hormone receptor; messenger RNA; protein Bax; thiobarbituric acid reactive substance; tyrosine 3 monooxygenase; adenosine A1 receptor; caffeine; central stimulant agent; cocaine; dopamine; dopamine 1 receptor; dopamine 2 receptor; dopamine uptake inhibitor; Drd1a protein, mouse; DRD2 protein, mouse; free radical; glutathione peroxidase; messenger RNA; primer DNA; thiobarbituric acid reactive substance; tyrosine 3 monooxygenase; animal cell; animal experiment; animal model; animal tissue; Article; cell loss; cell proliferation; cellular distribution; controlled study; disease association; dopaminergic system; down regulation; gene expression regulation; germ cell; intoxication; Leydig cell; lipid peroxidation; long term exposure; male; male genital tract parameters; meiotic germs cell; mouse; nonhuman; protein expression; psychostimulant induced testicular toxicity; seminiferous tubule volume; Sertoli cell; spermatogonium; testis disease; transgenic mouse; upregulation; animal; apoptosis; C57BL mouse; cytoplasm; drug effects; genetic epigenesis; immunohistochemistry; metabolism; testis; Animals; Apoptosis; Caffeine; Cell Proliferation; Central Nervous System Stimulants; Cocaine; Cytoplasm; DNA Primers; Dopamine; Dopamine Uptake Inhibitors; Epigenesis, Genetic; Free Radicals; Glutathione Peroxidase; Immunohistochemistry; Leydig Cells; Male; Mice; Mice, Inbred C57BL; Receptor, Adenosine A1; Receptors, Dopamine D1; Receptors, Dopamine D2; RNA, Messenger; Spermatogonia; Testis; Thiobarbituric Acid Reactive Substances; Tyrosine 3-Monooxygenase
Año:2015
Volumen:10
Número:11
DOI: http://dx.doi.org/10.1371/journal.pone.0142713
Título revista:PLoS ONE
Título revista abreviado:PLoS ONE
ISSN:19326203
CODEN:POLNC
CAS:caffeine, 58-08-2; catalase, 9001-05-2; cocaine, 50-36-2, 53-21-4, 5937-29-1; copper zinc superoxide dismutase, 149394-67-2; glutathione peroxidase, 9013-66-5; tyrosine 3 monooxygenase, 9036-22-0; dopamine, 51-61-6, 62-31-7; Caffeine; Central Nervous System Stimulants; Cocaine; DNA Primers; Dopamine; Dopamine Uptake Inhibitors; Drd1a protein, mouse; DRD2 protein, mouse; Free Radicals; Glutathione Peroxidase; Receptor, Adenosine A1; Receptors, Dopamine D1; Receptors, Dopamine D2; RNA, Messenger; Thiobarbituric Acid Reactive Substances; Tyrosine 3-Monooxygenase
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v10_n11_p_Gonzalez

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Citas:

---------- APA ----------
Gonzalez, C.R., Gonzalez, B., Matzkin, M.E., Muniz, J.A., Cadet, J.L., Garcia-Rill, E., Urbano, F.J.,..., Bisagno, V. (2015) . Psychostimulant-induced testicular toxicity in mice: Evidence of cocaine and caffeine effects on the local dopaminergic system. PLoS ONE, 10(11).
http://dx.doi.org/10.1371/journal.pone.0142713
---------- CHICAGO ----------
Gonzalez, C.R., Gonzalez, B., Matzkin, M.E., Muniz, J.A., Cadet, J.L., Garcia-Rill, E., et al. "Psychostimulant-induced testicular toxicity in mice: Evidence of cocaine and caffeine effects on the local dopaminergic system" . PLoS ONE 10, no. 11 (2015).
http://dx.doi.org/10.1371/journal.pone.0142713
---------- MLA ----------
Gonzalez, C.R., Gonzalez, B., Matzkin, M.E., Muniz, J.A., Cadet, J.L., Garcia-Rill, E., et al. "Psychostimulant-induced testicular toxicity in mice: Evidence of cocaine and caffeine effects on the local dopaminergic system" . PLoS ONE, vol. 10, no. 11, 2015.
http://dx.doi.org/10.1371/journal.pone.0142713
---------- VANCOUVER ----------
Gonzalez, C.R., Gonzalez, B., Matzkin, M.E., Muniz, J.A., Cadet, J.L., Garcia-Rill, E., et al. Psychostimulant-induced testicular toxicity in mice: Evidence of cocaine and caffeine effects on the local dopaminergic system. PLoS ONE. 2015;10(11).
http://dx.doi.org/10.1371/journal.pone.0142713