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Volume 20
Issue 7
10.3390/ijms20071556
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Article

Lack of Rhes Increases MDMA-Induced Neuroinflammation and Dopamine Neuron Degeneration: Role of Gender and Age

by
Giulia Costa
1,
Pier Francesca Porceddu
1,
Marcello Serra
1,
Maria Antonietta Casu
2,
Valentina Schiano
3,
Francesco Napolitano
3,4,
Annalisa Pinna
5,*,
Alessandro Usiello
3,6 and
Micaela Morelli
1,5,7
1
Department of Biomedical Sciences, Section of Neuroscience, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy
2
Institute of Translational Pharmacology, UOS of Cagliari, National Research Council of Italy, Scientific and Technological Park of Sardinia POLARIS, 09010 Pula, Italy
3
Laboratory of Behavioral Neuroscience, Ceinge Biotecnologie Avanzate, 80145 Naples, Italy
4
Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, 80131 Naples, Italy
5
Neuroscience Institute, National Research Council of Italy, Cittadella Universitaria, 09042 Monserrato, Italy
6
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, Luigi Vanvitelli, 81100 Caserta, Italy
7
National Institute of Neuroscience (INN), University of Cagliari, 09100 Cagliari, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(7), 1556; https://doi.org/10.3390/ijms20071556
Received: 15 February 2019 / Revised: 21 March 2019 / Accepted: 24 March 2019 / Published: 28 March 2019
(This article belongs to the Special Issue Neuroinflammation and Psychiatric Disorders: From Mechanisms to Therapy Potential)
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Abstract

Ras homolog enriched in striatum (Rhes) is a protein that exerts important physiological functions and modulates psychostimulant drug effects. On this basis, the object of this study was to assess 3,4-methylenedioxymethamphetamine (MDMA) effects on microglial (CD11b) and astroglial (GFAP) activation and on dopamine neuron degeneration (TH) in wild-type (WT) and Rhes knockout (KO) male and female mice of different ages. Motor activity was also evaluated. Adult (3 months) MDMA-treated mice displayed an increase in GFAP-positive cells in striatum (STR), whereas the substantia nigra pars compacta (SNc) was affected only in male mice. In these mice, the increase of CD11b was more extensive including STR, SNc, motor cortex (CTX), ventral tegmental area (VTA), and nucleus accumbens (NAc). MDMA administration also affected TH immunoreactivity in both STR and SNc of male but not female WT and Rhes KO mice. In middle-aged mice (12 months), MDMA administration further increased GFAP and CD11b and decreased TH immunoreactivity in STR and SNc of all mice. Finally, MDMA induced a higher increase of motor activity in adult Rhes KO male, but not female mice. The results show that Rhes protein plays an important role on MDMA-mediated neuroinflammation and neurodegeneration dependent on gender and age, and confirm the important role of Rhes protein in neuroinflammatory and neurodegenerative processes. View Full-Text
Keywords: astrocytes; microglia; neurodegeneration; dopamine; MDMA; Rhes knockout mice; psychosis astrocytes; microglia; neurodegeneration; dopamine; MDMA; Rhes knockout mice; psychosis
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MDPI and ACS Style

Costa, G.; Porceddu, P.F.; Serra, M.; Casu, M.A.; Schiano, V.; Napolitano, F.; Pinna, A.; Usiello, A.; Morelli, M. Lack of Rhes Increases MDMA-Induced Neuroinflammation and Dopamine Neuron Degeneration: Role of Gender and Age. Int. J. Mol. Sci. 2019, 20, 1556. https://doi.org/10.3390/ijms20071556

AMA Style

Costa G, Porceddu PF, Serra M, Casu MA, Schiano V, Napolitano F, Pinna A, Usiello A, Morelli M. Lack of Rhes Increases MDMA-Induced Neuroinflammation and Dopamine Neuron Degeneration: Role of Gender and Age. International Journal of Molecular Sciences. 2019; 20(7):1556. https://doi.org/10.3390/ijms20071556

Chicago/Turabian Style

Costa, Giulia, Pier F. Porceddu, Marcello Serra, Maria A. Casu, Valentina Schiano, Francesco Napolitano, Annalisa Pinna, Alessandro Usiello, and Micaela Morelli. 2019. "Lack of Rhes Increases MDMA-Induced Neuroinflammation and Dopamine Neuron Degeneration: Role of Gender and Age" International Journal of Molecular Sciences 20, no. 7: 1556. https://doi.org/10.3390/ijms20071556

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