ROS and sympathetically mediated mitochondria activation in brown adipose tissue contribute to methamphetamine-induced hyperthermia

Manuel Sanchez-Alavez, Bruno Conti, Malcolm R. Wood, Nikki Bortell, Eduardo Bustamante, Enrique Saez, Howard S Fox, Maria Cecilia Garibaldi Marcondes

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Methamphetamine (Meth) abuse has been shown to induce alterations in mitochondrial function in the brain as well as to induce hyperthermia, which contributes to neurotoxicity and Meth-associated mortality. Brown adipose tissue (BAT), a thermogenic site known to be important in neonates, has recently regained importance since being identified in significant amounts and in correlation with metabolic balance in human adults. Given the high mitochondrial content of BAT and its role in thermogenesis, we aimed to investigate whether BAT plays any role in the development of Meth-induced hyperthermia. By ablating or denervating BAT, we identified a partial contribution of this organ to Meth-induced hyperthermia. BAT ablation decreased temperature by 0.5°C and reduced the length of hyperthermia by 1 h, compared to sham-operated controls. BAT denervation also affected the development of hyperthermia in correlation with decreased the expression of electron transport chain molecules, and increase on PCG1a levels, but without affecting Meth-induced uncoupling protein 1 upregulation. Furthermore, in isolated BAT cells in culture, Meth, but not Norepinephrine, induced H2O2 upregulation. In addition, we found that in vivo Reactive Oxygen Species (ROS) play a role in Meth hyperthermia. Thus, sympathetically mediated mitochondrial activation in the BAT and Meth-induced ROS are key components to the development of hyperthermia in Meth abuse.

Original languageEnglish (US)
Article numberArticle 44
JournalFrontiers in Endocrinology
Volume4
Issue numberAPR
DOIs
StatePublished - Sep 20 2013

Fingerprint

Induced Hyperthermia
Brown Adipose Tissue
Methamphetamine
Reactive Oxygen Species
Mitochondria
Fever
Up-Regulation
Thermogenesis
Denervation
Electron Transport
Norepinephrine
Cell Culture Techniques
Temperature
Mortality

Keywords

  • Brown adipose tissue
  • Hyperthermia
  • Methamphetamine
  • Mitochondria
  • Thermogenesis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Sanchez-Alavez, M., Conti, B., Wood, M. R., Bortell, N., Bustamante, E., Saez, E., ... Marcondes, M. C. G. (2013). ROS and sympathetically mediated mitochondria activation in brown adipose tissue contribute to methamphetamine-induced hyperthermia. Frontiers in Endocrinology, 4(APR), [Article 44]. https://doi.org/10.3389/fendo.2013.00044

ROS and sympathetically mediated mitochondria activation in brown adipose tissue contribute to methamphetamine-induced hyperthermia. / Sanchez-Alavez, Manuel; Conti, Bruno; Wood, Malcolm R.; Bortell, Nikki; Bustamante, Eduardo; Saez, Enrique; Fox, Howard S; Marcondes, Maria Cecilia Garibaldi.

In: Frontiers in Endocrinology, Vol. 4, No. APR, Article 44, 20.09.2013.

Research output: Contribution to journalArticle

Sanchez-Alavez, Manuel ; Conti, Bruno ; Wood, Malcolm R. ; Bortell, Nikki ; Bustamante, Eduardo ; Saez, Enrique ; Fox, Howard S ; Marcondes, Maria Cecilia Garibaldi. / ROS and sympathetically mediated mitochondria activation in brown adipose tissue contribute to methamphetamine-induced hyperthermia. In: Frontiers in Endocrinology. 2013 ; Vol. 4, No. APR.
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