A Hypothesis: multiple factors associated with lack of beneficial effects of estrogen replacement therapy in the late postmenopausal stage
ABSTRACT 1. Epidemiological and clinical studies suggest that women may obtain cognitive benefits from oestrogen-replacement therapy (ERT) during menopause transition rather than in the post-menopausal stages. However, the underlying mechanisms remain to be determined. 2. We propose that long-term oestrogen deficiency may result in abnormal distribution and localization of brain oestrogen receptors, brain mitochondrial dysfunction, septohippocampal cholinergic degeneration and reactive gliosis. These multiple pathogenic factors may account for the lack of any beneficial effects of ERT in post-menopausal women with or without Alzheimer's disease.
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ABSTRACT: Because estrogen plays important neurotrophic and neuroprotective roles in the brain by activating estrogen receptors (ERs), disruption of normal estrogen signaling can leave neurons vulnerable to a variety of insults, including β-amyloid peptide (Aβ). Aroclor1254 (A1254) belongs to the endocrine-disrupting chemical (EDC) polychlorinated biphenyls and has anti-estrogenic properties. In the present study, we evaluated the effect of A1254 on the protective activity of estrogen against Aβ toxicity in differentiated cholinergic SN56 cells. Aged Aβ25-35 causes apoptotic cell death in differentiated SN56 cells, and the cytotoxic evidences are effectively rescued by estrogen. We found that A1254 abolishes the neuroprotective activity of estrogen against Aβ toxicity, and attenuates the suppressive effect of estrogen on Aβ-induced tau phosphorylation and JNK activation. The effects of A1254 on the neuroprotective effects of estrogen in Aβ toxicity are very similar to the effects of the estrogen receptor antagonist ICI182,780. Thus, exposure to EDCs that have anti-estrogenic activity might interfere with normal estrogen-activated neuroprotective signaling events and leave neurons more vulnerable to dangerous stimuli. Our present results provide new understanding of the mechanisms contributing to the harmful effects of EDCs on the function and viability of neurons, and the possible relevance of EDCs in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease.Neurochemistry International 06/2011; 59(5):582-90. DOI:10.1016/j.neuint.2011.04.006 · 3.09 Impact Factor
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ABSTRACT: A full-length ribosomal protein L15 cDNA from Chironomus riparius (CrRPL15) was identified from the Expressed Sequence Tag (EST) database developed vt 454 pyrosequencing, and expression of the corresponding mRNA was analyzed during different developmental stages and following exposure to Cadmium chloride (Cd) and Silver nanoparticles (AgNPs). The CrRPL15 cDNA contains an open reading frame (ORF) of 615 base pairs (bp) encoding a putative protein of 204 amino acids, with a high level of sequence similarity to RPL15 proteins from other species. The consensus sequence, GXXXXGKS, which is present in other RPL15 proteins, was also present in the putative CrRPL15 protein. The CrRPL15 transcript was present at all life stages, but was most abundant in the eggs. Expression of the CrRPL15 gene was significantly down-regulated in response to exposure to both Cd and AgNPs. In contrast, expression of the heat shock protein 70 (HSP70) gene, a general stress indicator, was significantly up-regulated.Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology 07/2011; 159(3):157-62. DOI:10.1016/j.cbpb.2011.03.006 · 1.55 Impact Factor