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Effect of crowding, temperature and age on glia activation and dopaminergic neurotoxicity induced by MDMA in the mouse brain.

Abstract

3,4-methylenedyoxymethamphetamine (MDMA or "ecstasy"), a recreational drug of abuse, can induce glia activation and dopaminergic neurotoxicity. Since MDMA is often consumed in crowded environments featuring high temperatures, we studied how these factors influenced glia activation and dopaminergic neurotoxicity induced by MDMA. C57BL/6J adolescent (4 weeks old) and adult (12 weeks old) mice received MDMA (4×20mg/kg) in different conditions: 1) while kept 1, 5, or 10×cage at room temperature (21°C); 2) while kept 5×cage at either room (21°C) or high (27°C) temperature. After the last MDMA administration, immunohistochemistry was performed in the caudate-putamen for CD11b and GFAP, to mark microglia and astroglia, and in the substantia nigra pars compacta for tyrosine hydroxylase, to mark dopaminergic neurons. MDMA induced glia activation and dopaminergic neurotoxicity, compared with vehicle administration. Crowding (5 or 10 mice×cage) amplified MDMA-induced glia activation (in adult and adolescent mice) and dopaminergic neurotoxicity (in adolescent mice). Conversely, exposure to a high environmental temperature (27°C) potentiated MDMA-induced glia activation in adult and adolescent mice kept 5×cage, but not dopaminergic neurotoxicity. Crowding and exposure to a high environmental temperature amplified MDMA-induced hyperthermia, and a positive correlation between body temperature and activation of either microglia or astroglia was found in adult and adolescent mice. These results provide further evidence that the administration setting influences the noxious effects of MDMA in the mouse brain. However, while crowding amplifies both glia activation and dopaminergic neurotoxicity, a high environmental temperature exacerbates glia activation only.

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  • Authors+Show Affiliations

    ,

    Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy. Electronic address: luciafrau79@hotmail.com.

    ,

    Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy. Electronic address: nicola.simola@gmail.com.

    ,

    Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy. Electronic address: fra8714@hotmail.it.

    Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy; CNR, Institute of Neuroscience, Cagliari, Italy. Electronic address: morelli@unica.it.

    Source

    Neurotoxicology 56: 2016 09 pg 127-138

    MeSH

    Aging
    Analysis of Variance
    Animals
    Body Temperature
    CD11b Antigen
    Crowding
    Disease Models, Animal
    Dopamine
    Dopaminergic Neurons
    Glial Fibrillary Acidic Protein
    Hallucinogens
    Male
    Mice
    Mice, Inbred C57BL
    N-Methyl-3,4-methylenedioxyamphetamine
    Neuroglia
    Neurotoxicity Syndromes
    Temperature
    Tyrosine 3-Monooxygenase

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    27451954

    Citation

    Frau, Lucia, et al. "Effect of Crowding, Temperature and Age On Glia Activation and Dopaminergic Neurotoxicity Induced By MDMA in the Mouse Brain." Neurotoxicology, vol. 56, 2016, pp. 127-138.
    Frau L, Simola N, Porceddu PF, et al. Effect of crowding, temperature and age on glia activation and dopaminergic neurotoxicity induced by MDMA in the mouse brain. Neurotoxicology. 2016;56:127-138.
    Frau, L., Simola, N., Porceddu, P. F., & Morelli, M. (2016). Effect of crowding, temperature and age on glia activation and dopaminergic neurotoxicity induced by MDMA in the mouse brain. Neurotoxicology, 56, pp. 127-138. doi:10.1016/j.neuro.2016.07.008.
    Frau L, et al. Effect of Crowding, Temperature and Age On Glia Activation and Dopaminergic Neurotoxicity Induced By MDMA in the Mouse Brain. Neurotoxicology. 2016;56:127-138. PubMed PMID: 27451954.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effect of crowding, temperature and age on glia activation and dopaminergic neurotoxicity induced by MDMA in the mouse brain. AU - Frau,Lucia, AU - Simola,Nicola, AU - Porceddu,Pier Francesca, AU - Morelli,Micaela, Y1 - 2016/07/21/ PY - 2016/04/22/received PY - 2016/07/15/revised PY - 2016/07/20/accepted PY - 2016/7/28/pubmed PY - 2017/11/29/medline PY - 2016/7/26/entrez KW - Aggregation KW - Cage density KW - Ecstasy KW - Glia KW - Hyperthermia KW - Neurodegeneration SP - 127 EP - 138 JF - Neurotoxicology JO - Neurotoxicology VL - 56 N2 - 3,4-methylenedyoxymethamphetamine (MDMA or "ecstasy"), a recreational drug of abuse, can induce glia activation and dopaminergic neurotoxicity. Since MDMA is often consumed in crowded environments featuring high temperatures, we studied how these factors influenced glia activation and dopaminergic neurotoxicity induced by MDMA. C57BL/6J adolescent (4 weeks old) and adult (12 weeks old) mice received MDMA (4×20mg/kg) in different conditions: 1) while kept 1, 5, or 10×cage at room temperature (21°C); 2) while kept 5×cage at either room (21°C) or high (27°C) temperature. After the last MDMA administration, immunohistochemistry was performed in the caudate-putamen for CD11b and GFAP, to mark microglia and astroglia, and in the substantia nigra pars compacta for tyrosine hydroxylase, to mark dopaminergic neurons. MDMA induced glia activation and dopaminergic neurotoxicity, compared with vehicle administration. Crowding (5 or 10 mice×cage) amplified MDMA-induced glia activation (in adult and adolescent mice) and dopaminergic neurotoxicity (in adolescent mice). Conversely, exposure to a high environmental temperature (27°C) potentiated MDMA-induced glia activation in adult and adolescent mice kept 5×cage, but not dopaminergic neurotoxicity. Crowding and exposure to a high environmental temperature amplified MDMA-induced hyperthermia, and a positive correlation between body temperature and activation of either microglia or astroglia was found in adult and adolescent mice. These results provide further evidence that the administration setting influences the noxious effects of MDMA in the mouse brain. However, while crowding amplifies both glia activation and dopaminergic neurotoxicity, a high environmental temperature exacerbates glia activation only. SN - 1872-9711 UR - https://www.unboundmedicine.com/medline/citation/27451954/Effect_of_crowding_temperature_and_age_on_glia_activation_and_dopaminergic_neurotoxicity_induced_by_MDMA_in_the_mouse_brain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-813X(16)30135-8 DB - PRIME DP - Unbound Medicine ER -