title: Critical period for dopaminergic neuroprotection by hormonal replacement in menopausal rats.
abstract: The neuroprotective effects of menopausal hormonal therapy in Parkinson's disease have not yet been clarified, and it is not known whether there is a critical period. Estrogen induced significant protection against 6-hydroxydopamine-induced dopaminergic degeneration when administered immediately or 6 weeks, but not 20 weeks after ovariectomy. In the substantia nigra, ovariectomy induced a decrease in levels of estrogen receptor-α and increased angiotensin activity, NADPH-oxidase activity, and expression of neuroinflammatory markers, which were regulated by estrogen administered immediately or 6 weeks but not 20 weeks after ovariectomy. Interestingly, treatment with angiotensin receptor antagonists after the critical period induced a significant level of neuroprotection. In cultures, treatment with 1-methyl-4-phenylpyridinium induced an increase in astrocyte-derived angiotensinogen and dopaminergic neuron death, which were inhibited by estrogen receptor α agonists. In microglial cells, estrogen receptor β agonists inhibited the angiotensin-induced increase in inflammatory markers. The results suggest that there is a critical period for the neuroprotective effect of estrogen against dopaminergic cell death, and local estrogen receptor α and renin-angiotensin system play a major role.
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Rodriguez-Perez
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Borrajo
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain.
authors.forename: Rita
authors.initials: R
authors.lastname: Valenzuela
authors.affiliation: Neurosciences Division, CIMA, University of Navarra, Pamplona, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Lanciego
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain. Electronic address: joseluis.labandeira@usc.es.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Labandeira-Garcia
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology*; D047628:Estrogen Receptor alpha / Q000502:physiology*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage* / Q000494:pharmacology*; D005260:Female; D008593:Menopause; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D018696:Neuroprotective Agents; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology*; D013997:Time Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D047628:Estrogen Receptor alpha; D004967:Estrogens; D018696:Neuroprotective Agents; D016627:Oxidopamine
keywords: Critical period; Estrogen; Menopause; Ovariectomy; Parkinson