Publication details

Influence of caffeine on 3,4-methylenedioxymethamphetamine-induced dopaminergic neuron degeneration and neuroinflammation is age-dependent

Authors	FRAU Lucia COSTA Giulia PORCEDDU Pier Francesca KHAIRNAR Amit Suresh CASTELLI Maria Paola ENNAS Maria Grazia MADEDDU Camilla WARDAS Jadwiga MORELLI Micaela
Year of publication	2016
Type	Article in Periodical
Magazine / Source	Journal of Neurochemistry
MU Faculty or unit	Central European Institute of Technology
Citation
Web	http://onlinelibrary.wiley.com/doi/10.1111/jnc.13377/epdf
Doi	http://dx.doi.org/10.1111/jnc.13377
Field	Neurology, neurosurgery, neurosciences
Keywords	adolescence; caudate-putamen; cytokines; nitric oxide; substantia nigra; tyrosine hydroxylase
Description	Previous studies have demonstrated that caffeine administration to adult mice potentiates glial activation induced by 3,4-methylenedioxymethamphetamine (MDMA). As neuroinflammatory response seems to correlate with neurodegeneration, and the young brain is particularly vulnerable to neurotoxicity, we evaluated dopamine neuron degeneration and glial activation in the caudate-putamen (CPu) and substantia nigra pars compacta (SNc) of adolescent and adult mice. Mice were treated with MDMA (4x20mg/kg), alone or with caffeine (10mg/kg). Interleukin (IL)-1, tumor necrosis factor (TNF)-, neuronal nitric oxide synthase (nNOS) were evaluated in CPu, whereas tyrosine hydroxylase (TH), glial fibrillary acidic protein, and CD11b were evaluated in CPu and SNc by immunohistochemistry. MDMA decreased TH in SNc of both adolescent and adult mice, whereas TH-positive fibers in CPu were only decreased in adults. In CPu of adolescent mice, caffeine potentiated MDMA-induced glial fibrillary acidic protein without altering CD11b, whereas in SNc caffeine did not influence MDMA-induced glial activation. nNOS, IL-1, and TNF- were increased by MDMA in CPu of adults, whereas in adolescents, levels were only elevated after combined MDMA plus caffeine. Caffeine alone modified only nNOS. Results suggest that the use of MDMA in association with caffeine during adolescence may exacerbate the neurotoxicity and neuroinflammation elicited by MDMA.