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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.
Ann N Y Acad Sci. 2005 Dec; 1057:296-318.AN

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 (E(2)) 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.

Authors+Show Affiliations

OASI Institute for Research and Care on Mental Retardation and Brain Aging (IRCCS), Neuropharmacology Section, Via Conte Ruggero 73, 94018 Troina (EN), Italy. bianca.marchetti@oasi.en.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

16399902

Citation

Marchetti, Bianca, et al. "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, 2005, pp. 296-318.
Marchetti B, Serra PA, L'Episcopo F, et al. Hormones are key actors in gene x environment interactions programming the vulnerability to Parkinson's disease: glia as a common final pathway. Ann N Y Acad Sci. 2005;1057:296-318.
Marchetti, B., Serra, P. A., L'Episcopo, F., Tirolo, C., Caniglia, S., Testa, N., Cioni, S., Gennuso, F., Rocchitta, G., Desole, M. S., Mazzarino, M. C., Miele, E., & Morale, M. C. (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, 1057, 296-318.
Marchetti B, et al. Hormones Are Key Actors in Gene X Environment Interactions Programming the Vulnerability to Parkinson's Disease: Glia as a Common Final Pathway. Ann N Y Acad Sci. 2005;1057:296-318. PubMed PMID: 16399902.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hormones are key actors in gene x environment interactions programming the vulnerability to Parkinson's disease: glia as a common final pathway. AU - Marchetti,Bianca, AU - Serra,Pier Andrea, AU - L'Episcopo,Francesca, AU - Tirolo,Cataldo, AU - Caniglia,Salvo, AU - Testa,Nuccio, AU - Cioni,Serena, AU - Gennuso,Florinda, AU - Rocchitta,Gaia, AU - Desole,Maria Speranza, AU - Mazzarino,Maria Clorinda, AU - Miele,Egidio, AU - Morale,Maria Concetta, PY - 2006/1/10/pubmed PY - 2006/7/13/medline PY - 2006/1/10/entrez SP - 296 EP - 318 JF - Annals of the New York Academy of Sciences JO - Ann N Y Acad Sci VL - 1057 N2 - 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 (E(2)) 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. SN - 0077-8923 UR - https://www.unboundmedicine.com/medline/citation/16399902/Hormones_are_key_actors_in_gene_x_environment_interactions_programming_the_vulnerability_to_Parkinson's_disease:_glia_as_a_common_final_pathway_ L2 - https://doi.org/10.1196/annals.1356.023 DB - PRIME DP - Unbound Medicine ER -