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Estrogen, neuroinflammation and neuroprotection in Parkinson's disease: glia dictates resistance versus vulnerability to neurodegeneration

Morale, Maria Concetta and Serra, Pier Andrea and L'Episcopo, Francesca and Tirolo, Cataldo and Caniglia, Salvo and Testa, Nuccio and Gennuso, Florinda and Giaquinta, Giovanna and Rocchitta, Gaia Giovanna Maria and Desole, Maria Speranza and Miele, Egidio and Marchetti, Bianca Maria (2006) Estrogen, neuroinflammation and neuroprotection in Parkinson's disease: glia dictates resistance versus vulnerability to neurodegeneration. Neuroscience, Vol. 138 (3), p. 869-878. ISSN 0306-4522. Article.

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DOI: 10.1016/j.neuroscience.2005.07.060

Abstract

Post-menopausal estrogen deficiency is recognized to play a pivotal role in the pathogenesis of a number of age-related diseases in women, such as osteoporosis, coronary heart disease and Alzheimer’s disease. There are also sexual differences in the progression of diseases associated with the nigrostriatal dopaminergic system, such as Parkinson’s disease, a chronic progressive degenerative disorder characterized by the selective degeneration of mesencephalic dopaminergic neurons in the substancia nigra pars compacta. The mechanism(s) responsible for dopaminergic neuron degeneration in Parkinson’s disease are still unknown, but oxidative stress and neuroinflammation are believed to play a key role in nigrostriatal dopaminergic neuron demise. Estrogen neuroprotective effects have been widely reported in a number of neuronal cell systems including the nigrostriatal dopaminergic neurons, via both genomic and non-genomic effects, however, little is known on estrogen modulation of astrocyte and microglia function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. We here highlight estrogen modulation of glial neuroinflammatory reaction in the protection of mesencephalic dopaminergic neurons and emphasize the cardinal role of glia-neuron crosstalk in directing neuroprotection vs neurodegeneration. In particular, the specific role of astroglia and its pro-/anti-inflammatory mechanisms in estrogen neuroprotection are presented. This study shows that astrocyte and microglia response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injury vary according to the estrogenic status with direct consequences for dopaminergic neuron survival, recovery and repair. These findings provide a new insight into the protective action of estrogen that may possibly contribute to the development of novel therapeutic treatment strategies for Parkinson’s disease.

Item Type:Article
ID Code:612
Status:Published
Refereed:Yes
Uncontrolled Keywords:Neurodegeneration, neuroinflammation, estrogens, glia–neuron crosstalk, neuroprotection
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Divisions:001 Università di Sassari > 01 Dipartimenti > Neuroscienze, scienze materno infantili
Publisher:Pergamon / Elsevier
ISSN:0306-4522
Copyright Holders:© 2005 IBRO
Deposited On:18 Aug 2009 10:02

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