Authors

Granado, N., Lastres-Becker, I., Ares-Santos, S., Oliva, I., Martin, E., Cuadrado, A., & Moratalla, R.

Affiliations

Instituto Cajal, CSIC, Madrid, Spain, Centro de Investigaciones en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain, Departamento de Farmacia, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain, Departamento de Bioquımica and Instituto de Investigaciones Biomedicas ‘‘Alberto Sols’’ UAM-CSIC, Facultad de Medicina, Universidad Autonoma de Madrid, and Instituto de Investigaci
on Sanitaria La Paz (IDIPAZ), Madrid, Spain, Laboratorio de Neurofisiologıa y Plasticidad Sin
aptica, Parque Cientıfico y Tecnologico de Albacete (PCYTA),Instituto de Investigacion en Discapacidades Neurologicas (IDINE), Universidad de Castilla-La Mancha, Albacete, Spain.

Application Area

Neuroscience

Immunofluorescence

Abstract

Oxidative stress that correlates with damage to nigrostriatal dopaminergic neurons and reactive gliosis in the basal ganglia is a hallmark of methamphetamine (METH) toxicity. In this study, we analysed the protective role of the transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2), a master regulator of redox homeostasis, in METH-induced neurotoxicity. We found that Nrf2 deficiency exacerbated METH-induced damage to dopamine neurons, shown by an increase in loss of tyrosine hydroxylase (TH) - and dopamine transporter (DAT)-containing fibres in striatum. Consistent with these effects, Nrf2 deficiency potentiated glial activation, indicated by increased striatal expression of markers for microglia (Mac-1 and Iba-1) and astroglia (GFAP) one day after METH administration. At the same time, Nrf2 inactivation dramatically potentiated the increase in TNFα mRNA and IL-15 protein expression in GFAP+ cells in the striatum. In sharp contrast to the potentiation of striatal damage, Nrf2 deficiency did not affect METH-induced dopaminergic neuron death or expression of glial markers or proinflammatory molecules in the substantia nigra. This study uncovers a new role for Nrf2 in protection against METH-induced inflammatory and oxidative stress and striatal degeneration.

Extract

… “Cells were illuminated during 200 ms with a LED excitation system (pE-2, CoolLED Limited, Andover, UK)” …

Product Associated Features

pE-2: A repeatable, controllable modular system with 20 different LED peaks. Instant on/off and intensity (0-100%) control

Diascopic Technique

-

Live Cell Issues

-

Product Type

-

Journal

Glia

Year of Publication

2011

Country of Publication

Spain