Age-related changes in the expression of ER-β mRNA in the female rat brain

Yamaguchi, Naoko; Yuri, Kazunari

doi:10.1016/j.brainres.2007.04.016

Cited by 40 publications

(35 citation statements)

References 72 publications

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“…With increasing attention on the sexually dimorphic nature of other brain regions, it is now apparent that the critical period for hormonal influences on sex differentiation may extend later into development and may involve androgen-as well as estrogen-dependent mechanisms. In particular, pubertal hormones may exert organizational influences on structures such as the hippocampus and amygdala as well as hypothalamic regions, including the anteroventricular periventricular nucleus and sexually dimorphic nucleus of the preoptic area (POA), where sex differences in regional volumes and the addition of new cells have been identified in humans and animals used in research (Williams, 1986; Gonad-intact-intact female brain: compared with young rats (10 weeks), numbers of ER␤ mRNA-positive cells were reduced in the olfactory bulb, cerebral cortex, hippocampus, N.Acc, parts of the amygdala and raphe nuclei in middle-age (12 months), but did not decline further in aged animals (24 months); by contrast, numbers in hippocampus, striatum, claustrum, SN and cerebellum did not change by middle-age, but decreased in old rats: age-dependent changes are region specific (Yamaguchi-Shima and Yuri, 2007).…”

Section: Mousementioning

confidence: 85%

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

2010

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Section: Mousementioning

confidence: 85%

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

2010

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“…PvuII and XbaI polymorphisms located in ER␣ (27)(28)(29) and five intronic single-nucleotide polymorphisms (30) in the ER␤ gene were identified as susceptibility factors for AD in women. Most interestingly, in the hippocampus of female rats, expression of ERs decreases with age (31,32). If a similar decrease occurs in human brain, it might explain the decreased efficacy of estrogen replacement therapy in older postmenopausal women (33).…”

Section: Discussionmentioning

confidence: 99%

Estrogen Stimulates Degradation of β-Amyloid Peptide by Up-regulating Neprilysin

Liang

Yang

Yin

et al. 2010

Journal of Biological Chemistry

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Postmenopausal estrogen depletion is a characterized risk factor for Alzheimer disease (AD), a human disorder linked to high levels of ␤-amyloid peptide (A␤) in brain tissue. Previous studies suggest that estrogen negatively regulates the level of A␤ in the brain, but the molecular mechanism is unknown. Here, we provide evidence that estrogen promotes A␤ degradation mainly through a principal A␤ degrading enzyme, neprilysin, in neuroblastoma SH-SY5Y cells. We also demonstrate that upregulation of neprilysin by estrogen is dependent on both estrogen receptor ␣ and ␤ (ER␣ and ER␤), and ligand-activated ER regulates expression of neprilysin through physical interactions between ER and estrogen response elements (EREs) identified in the neprilysin gene. These results were confirmed by in vitro gel shift and in vivo chromatin immunoprecipitation analyses, which demonstrate specific binding of ER␣ and ER␤ to two putative EREs in the neprilysin gene. The EREs also enhance ER␣-and ER␤-dependent reporter gene expression in a yeast model system. Therefore, the study described here provides a putative mechanism by which estrogen positively regulates expression of neprilysin to promote degradation of A␤, reducing risk for AD. These results may lead to novel approaches to prevent or treat AD.Alzheimer disease (AD) 3 is a progressive neurodegenerative disease characterized by declarative memory impairment and progressive dementia. The level of ␤-amyloid peptide (A␤) is elevated in the brains of AD patients, and A␤ is believed to play a critical role in the pathology of AD (1, 2). Recent studies show that aggregated oligomers of A␤ (protofibrils) play a direct role in neuronal and behavioral deficits in AD patients (3).The rate of A␤ degradation could influence the risk of developing AD, and it has been proposed that stimulation of proteolytic degradation of A␤ could be used as a therapeutic approach for AD (4, 5). Neprilysin is thought to be the primary A␤-degrading enzyme in the brain (6) because degradation of radiolabeled synthetic A␤42 in rat brain is largely inhibited by the neprilysin inhibitor, phosphoramidon (PA) (7, 8) and because neprilysin degrades both monomeric and oligomeric forms of A␤40 and A␤42 in intracellular and extracellular compartments of the brain (9). Moreover, the level of neprilysin mRNA and protein is lower in the hippocampus and temporal gyrus of AD patients (10, 11), which correlates with higher levels of A␤ as A␤ tends to accumulate in these regions (12).Neprilysin activity is also lower in the hippocampus, cerebellum, and caudate of ovariectomized rats than in non-ovariectomized rats, and this effect can be reversed by exogenous 17␤-estradiol (13). These data indicate that 17␤-estradiol positively regulates neprilysin activity in the brain. 17␤-Estradiol was also reported to reduce the generation of A␤ peptides in neuroblastoma cells and neurons (14). The positive regulation of neprilysin by 17␤-estradiol might be a crucial factor in protecting normal adult brain from A␤ damage and in improving...

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“…ER ␤ expression decreases with age in the hippocampus but persists in the cortex (243). Estrogen regulation of ER ␤ mRNA declines in middle age (231); however, postsynaptic protein expression does not decline in aged female rats and retains the ability to be upregulated by estradiol replacement (227).…”

Section: Rodents Young Versus Agedmentioning

confidence: 98%

Estrogen Effects on Cognitive and Synaptic Health Over the Lifecourse

Hara

Waters

McEwen

et al. 2015

Physiological Reviews

333

249

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Estrogen facilitates higher cognitive functions by exerting effects on brain regions such as the prefrontal cortex and hippocampus. Estrogen induces spinogenesis and synaptogenesis in these two brain regions and also initiates a complex set of signal transduction pathways via estrogen receptors (ERs). Along with the classical genomic effects mediated by activation of ER α and ER β, there are membrane-bound ER α, ER β, and G protein-coupled estrogen receptor 1 (GPER1) that can mediate rapid nongenomic effects. All key ERs present throughout the body are also present in synapses of the hippocampus and prefrontal cortex. This review summarizes estrogen actions in the brain from the standpoint of their effects on synapse structure and function, noting also the synergistic role of progesterone. We first begin with a review of ER subtypes in the brain and how their abundance and distributions are altered with aging and estrogen loss (e.g., ovariectomy or menopause) in the rodent, monkey, and human brain. As there is much evidence that estrogen loss induced by menopause can exacerbate the effects of aging on cognitive functions, we then review the clinical trials of hormone replacement therapies and their effectiveness on cognitive symptoms experienced by women. Finally, we summarize studies carried out in nonhuman primate models of age- and menopause-related cognitive decline that are highly relevant for developing effective interventions for menopausal women. Together, we highlight a new understanding of how estrogen affects higher cognitive functions and synaptic health that go well beyond its effects on reproduction.

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Age-related changes in the expression of ER-β mRNA in the female rat brain

Cited by 40 publications

References 72 publications

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

Estrogen Stimulates Degradation of β-Amyloid Peptide by Up-regulating Neprilysin

Estrogen Effects on Cognitive and Synaptic Health Over the Lifecourse

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