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Estrogen Modulates Neuronal Bcl‐x l Expression and β‐Amyloid‐Induced Apoptosis
Author(s) -
Pike Christian J.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.721552.x
Subject(s) - estrogen , neuroprotection , neurodegeneration , biology , neurotoxicity , hippocampal formation , estrogen receptor , amyloid precursor protein , colocalization , medicine , alzheimer's disease , neuroscience , endocrinology , disease , genetics , toxicity , cancer , breast cancer
Recent findings indicate that estrogen is neuroprotective, a cellular effect that may contribute to its clinical benefits in delaying the development of Alzheimer’s disease. In this report, we identify a novel neuronal action of estrogen that may contribute to its neuroprotective mechanism(s). Specifically, we report that estrogen significantly increases the expression of the antiapoptotic protin Bcl‐X L in cultured hippocampal neurons. This effect presumably reflects classic estrogen transcriptional regulation, as we identified a putative estrogen response element in the bcl‐X gene. Estrogen‐induced enhancement of Bcl‐X L is associated with a reduction in measures of β‐amyloid‐induced apoptosis, including inhibition of both caspase‐mediated proteolysis and neurotoxicity. A similar relationship between estrogen, Bcl‐X L expression, and resistance to degeneration was also observed in human hippocampus. We report neuronal colocalization of estrogen receptor and Bcl‐X L immunoreactivities that is most prominent in hippocampal subfield CA3, a region that shows relatively little immunoreactivity to paired helical filament‐1, a marker of Alzheimer’s disease neurodegeneration. These data suggest a novel mechanism of estrogen neuroprotection that may be relevant to estrogen’s suggested ability to modulate neuronal viability across the life span, from neural sexual differentiation and development through age‐related neurodegenerative conditions.