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

被引：19

作者：

Costa, Giulia ^{[1
]}

Porceddu, Pier Francesca ^{[1
]}

Serra, Marcello ^{[1
]}

Casu, Maria Antonietta ^{[2
]}

Schiano, Valentina ^{[3
]}

Napolitano, Francesco ^{[3
,4
]}

Pinna, Annalisa ^{[5
]}

Usiello, Alessandro ^{[3
,6
]}

Morelli, Micaela ^{[1
,5
,7
]}

机构：

[1] Univ Cagliari, Dept Biomed Sci, Sect Neurosci, Cittadella Univ, I-09042 Monserrato, Italy

[2] Natl Res Council Italy, UOS Cagliari, Inst Translat Pharmacol, Sci & Technol Pk Sardinia POLARIS, I-09010 Pula, Italy

[3] Ceinge Biotecnol Avanzate, Lab Behav Neurosci, I-80145 Naples, Italy

[4] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, I-80131 Naples, Italy

[5] Natl Res Council Italy, Neurosci Inst, Cittadella Univ, I-09042 Monserrato, Italy

[6] Univ Campania, Dept Environm Biol & Pharmaceut Sci & Technol, I-81100 Luigi Vanvitelli, Caserta, Italy

[7] Univ Cagliari, Natl Inst Neurosci INN, I-09100 Cagliari, Italy

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 07期

关键词：

astrocytes; microglia; neurodegeneration; dopamine; MDMA; Rhes knockout mice; psychosis; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; MICROGLIAL ACTIVATION; SUBSTANTIA-NIGRA; GLIA ACTIVATION; PARKINSONS; NEUROTOXICITY; TEMPERATURE; ECSTASY; BRAIN; MICE;

D O I：

10.3390/ijms20071556

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：20