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Neuroprotection by estrogen in animal models of ischemia and Parkinson's disease
Author(s) -
Merchenthaler Istvan,
Shughrue Paul J.
Publication year - 2005
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20056
Subject(s) - neuroprotection , estrogen , estrogen receptor , striatum , mptp , ovariectomized rat , substantia nigra , medicine , neurodegeneration , endocrinology , ischemia , hippocampal formation , neuroscience , pharmacology , parkinson's disease , biology , dopamine , disease , cancer , breast cancer
Estrogen has been demonstrated to protect against brain injury, neurodegeneration, and cognitive decline. Furthermore, estrogen seems to specifically protect cortical and hippocampal neurons from ischemic injury. Here, the neuroprotective affects of estrogens, selective estrogen receptor modulators (SERMs), and estrogen receptor α‐ and β‐ (ERα and ERβ) selective ligands in animal models of focal and global ischemia are reviewed. In rats and mice, the middle cerebral artery occlusion (MCAO) model has been used as a model representing cerebrovascular stroke, while in gerbils the two‐vessel occlusion model, representing acute heart attack, has been used. Using focal ischemia in ovariectomized ERαKO, ERβKO, and wild type mice, it has been clearly established that the ERα subtype is critical for mediating neuroprotection in this model. The gerbil global ischemia model was used to evaluate the neuroprotective effects of estrogen, SERMs, and ERα‐ and ERβ‐selective compounds in the hippocampus. Analysis of neurogranin mRNA, a marker of viability of hippocampal neurons, with in situ hybridization, revealed that estrogen treatment resulted in complete protection in the dorsal CA1 regions, not only when administered before, but also when given 1 h after occlusion. The neuroprotection conferred by estrogen in an animal model of Parkinson's disease is also discussed. In the model of Parkinson's disease, although estrogen prevented the loss of tyrosine hydroxylase immunoreactivity in the striatum following 1‐methyl‐4‐phenyl‐1,2,3,6 tetrahydropyridine (MPTP) treatment, the lesion and/or the estrogen treatment did not induce the expression of ERs in the striatum or substantia nigra, indicating a non‐ER‐mediating effect of estrogen. Drug Dev. Res. 66:172–181, 2006. © 2006 Wiley‐Liss, Inc.