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574 results on '"Hirsch, Etienne C."'

17. Microglial glucocorticoid receptors play a pivotal role in regulating dopaminergic neurodegeneration in parkinsonism

Author

Ros-Bernal, Francisco, Hunot, Stéphane, Herrero, Maria Trinidad, Parnadeau, Sebastien, Corvol, Jean-Christophe, Lu, Lixia, Alvarez-Fischer, Daniel, Carrillo-de Sauvage, María Angeles, Saurini, Françoise, Coussieu, Christiane, Kinugawa, Kiyoka, Prigent, Annick, Höglinger, Günter, Hamon, Michel, Tronche, François, Hirsch, Etienne C., Vyas, Sheela, and Gage, Fred H.

Published
2011

32. Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease

Author

Karachi, Carine, Grabli, David, Bernard, Frederic A., Tande, Dominique, Wattiez, Nicolas, Belaid, Hayat, Bardinet, Eric, Prigent, Annick, Nothacker, Hans-Peter, Hunot, Stephane, Hartmann, Andreas, Lehericy, Stephane, Hirsch, Etienne C., and Francois, Chantal

Subjects
Mesencephalon -- Properties -- Physiological aspects, Neurons -- Properties -- Physiological aspects, Parkinson's disease -- Physiological aspects, Gait -- Observations -- Physiological aspects, Posture -- Observations -- Physiological aspects, Health care industry
Abstract

Gait disorders and postural instability, which are commonly observed in elderly patients with Parkinson disease (PD), respond poorly to dopaminergic agents used to treat other parkinsonian symptoms. The brain structures underlying gait disorders and falls in PD and aging remain to be characterized. Using functional MRI in healthy human subjects, we have shown here that activity of the mesencephalic locomotor region (MLR), which is composed of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus, was modulated by the speed of imagined gait, with faster imagined gait activating a discrete cluster within the MLR. Furthermore, the presence of gait disorders in patients with PD and in aged monkeys rendered parkinsonian by MPTP intoxication correlated with loss of PPN cholinergic neurons. Bilateral lesioning of the cholinergic part of the PPN induced gait and postural deficits in nondopaminergic lesioned monkeys. Our data therefore reveal that the cholinergic neurons of the PPN play a central role in controlling gait and posture and represent a possible target for pharmacological treatment of gait disorders in PD., Introduction Gait disorders and postural instability represent a major burden in the elderly population and are commonly observed in severe and advanced forms of Parkinson disease (PD; ref. 1). While [...]

Published
2010
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33. Infiltration of [CD4.sup.+] lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease

Author

Brochard, Vanessa, Combadiere, Behazine, Prigent, Annick, Laouar, Yasmina, Perrin, Aline, Beray-Berthat, Virginie, Bonduelle, Olivia, Alvarez-Fischer, Daniel, Callebert, Jacques, Launay, Jean-Marie, Duyckaerts, Charles, Flavell, Richard A., Hirsch, Etienne C., and Hunot, Stephane

Subjects
CD4 lymphocytes -- Physiological aspects, CD4 lymphocytes -- Health aspects, Interferon -- Physiological aspects, Interferon -- Genetic aspects, Parkinson's disease -- Risk factors, Parkinson's disease -- Genetic aspects, Parkinson's disease -- Research
Abstract

Parkinson disease (PD) is a neurodegenerative disorder characterized by a loss of dopamine-containing neurons. Mounting evidence suggests that dopaminergic cell death is influenced by the innate immune system. However, the pathogenic role of the adaptive immune system in PD remains enigmatic. Here we showed that [CD8.sup.+] and [CD4.sup.+] T cells but not B cells had invaded the brain in both postmortem human PD specimens and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD during the course of neuronal degeneration. We further demonstrated that MPTP-induced dopaminergic cell death was markedly attenuated in the absence of mature T lymphocytes in 2 different immunodeficient mouse strains (Rag1-/- and Tcrb-/- mice). Importantly, similar attenuation of MPTP-induced dopaminergic cell death was seen in mice lacking CD4 as well as in Rag1-/- mice reconstituted with FasL-deficient splenocytes. However, mice lacking CD8 and Rag1-/- mice reconstituted with IFN-[gamma]--deficient splenocytes were not protected. These data indicate that T cell--mediated dopaminergic toxicity is almost exclusively arbitrated by [CD4.sup.+] T cells and requires the expression of FasL but not IFN[gamma]. Further, our data may provide a rationale for targeting the adaptive arm of the immune system as a therapeutic strategy in PD., Introduction Parkinson disease (PD) is a neurodegenerative disorder characterized by the loss of dopamine-containing neurons (DNs) in the substantia nigra (SN) pars compacta (SNpc). Except for rare genetic forms, PD [...]

Published
2009

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