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Hormones are key actors in gene X environment interactions programming the vulnerability to Parkinson's disease: glia as a common final pathway

Marchetti, Bianca Maria and Serra, Pier Andrea and L'Episcopo, Francesca and Tirolo, Cataldo and Caniglia, Salvo and Testa, Nuccio and Cioni, Serena and Gennuso, Florinda and Rocchitta, Gaia Giovanna Maria and Desole, Maria Speranza and Mazzarino, Maria Clorinda and Miele, Egidio and Morale, Maria Concetta (2005) Hormones are key actors in gene X environment interactions programming the vulnerability to Parkinson's disease: glia as a common final pathway. Annals of the New York Academy of Sciences, Vol. 1057 (Reversal of aging resetting the pineal clock), p. 296-318. eISSN 1749-6632. Article.

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DOI: 10.1196/annals.1356.023

Abstract

Alterations in developmental programming of neuroendocrine and immune system function may critically modulate vulnerability to various diseases. In particular, genetic factors, including gender, may interact with early life events such as exposure to hormones, endotoxins, or neurotoxins, thereby influencing disease predisposition and/or severity, but little is known about the role of the astroglial cell compartment and its mediators in this phenomenon. Indeed, in the context of innate inflammatory mechanisms, a dysfunction of the astroglial cell compartment is believed to contribute to the selective degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta in Parkinson's disease (PD) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. Hence, in response to brain injury the roles of astrocytes and microglia are very dynamic and cell type-dependent, in that they may exert the known proinflammatory (harmful) effects, but in certain circumstances they can turn into highly protective cells and exert anti-inflammatory (beneficial) functions, thereby facilitating neuronal recovery and repair. Here, we summarize our work suggesting a chief role of hormonal programming of glial response to inflammation and oxidative stress in MPTP-induced loss of DA neuron functionality and demonstrate that endogenous glucocorticoids and the female hormone estrogen (E2) inhibit the aberrant neuroinflammatory cascade, protect astrocytes and microglia from programmed cell death, and stimulate recovery of DA neuron functionality, thereby triggering the repair process. The overall results highlight glia as a final common pathway directing neuroprotection versus neurodegeneration. Such recognition of endogenous glial protective pathways may provide a new insight and may contribute to the development of novel therapeutic treatment strategies for PD and possibly other neurodegenerative disorders.

Item Type:Article
ID Code:2445
Status:Published
Refereed:Yes
Uncontrolled Keywords:Parkinson's disease, glia, genes, environment, hormones, neuroinflammation, neurodegeneration, dopaminergic neurons, neuroprotection
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Divisions:001 Università di Sassari > 01 Dipartimenti > Neuroscienze, scienze materno infantili
Publisher:Blackwell / Wiley
eISSN:1749-6632
Copyright Holders:© 2005 New York Academy of Sciences
Additional Information:Pubblicato online il 23.01.06
Deposited On:18 Aug 2009 10:07

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