Enhanced Hyperthermia Induced by MDMA in Parkin Knockout Mice

Y.      Takamatsu; H.      Shiotsuki; S.      Kasai; S.      Sato; T.      Iwamura; N.      Hattori; K.      Ikeda

doi:10.2174/157015911795016985

Abstract

MDMA (3,4-methylenedioxymethamphetamine) is reportedly severely toxic to both dopamine (DA) and serotonin neurons. MDMA significantly reduces the number of DA neurons in the substantia nigra, but not in the nucleus accumbens, indicating that MDMA causes selective destruction of DA neurons in the nigrostriatal pathway, sparing the mesolimbic pathway. Parkinsons disease (PD) is a neurodegenerative disorder of multifactorial origin. The pathological hallmark of PD is the degeneration of DA neurons in the nigrostriatal pathway. Mutations in the parkin gene are frequently observed in autosomal recessive parkinsonism in humans. Parkin is hypothesized to protect against neurotoxic insult, and we attempted to clarify the role of parkin in MDMA-induced hyperthermia, one of the causal factors of neuronal damage, using parkin knockout mice. Body temperature was measured rectally before and 15, 30, 45, and 60 min after intraperitoneal injection of MDMA (30 mg/kg) at an ambient temperature of 22 ± 2°C. Significantly enhanced hyperthermia after MDMA injection was observed in heterozygous and homozygous parkin knockout mice compared with wildtype mice, suggesting that parkin plays a protective role in MDMA neurotoxicity.

Keywords: Hyperthermia, knockout, mice, MDMA, parkin, Serotonin, Dopamine, DA Transporter (DAT), E3 ubiquitin-protein ligase, DA ergeic Neuron, Neurotoxicity, receptor toxicity, Dopamine Transporter