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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
Author(s) -
MARCHETTI BIANCA,
SERRA PIER ANDREA,
L'EPISCOPO FRANCESCA,
TIROLO CATALDO,
CANIGLIA SALVO,
TESTA NUCCIO,
CIONI SERENA,
GENNUSO FLORINDA,
ROCCHITTA GAIA,
DESOLE MARIA SPERANZA,
MAZZARINO MARIA CLORINDA,
MIELE EGIDIO,
MORALE MARIA CONCETTA
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1356.023
Subject(s) - neurodegeneration , neuroprotection , neuroscience , pars compacta , microglia , neuroinflammation , substantia nigra , biology , proinflammatory cytokine , mptp , oligodendrocyte , parkinson's disease , dopaminergic , inflammation , dopamine , immunology , medicine , central nervous system , disease , myelin
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.