Estrogen Enhances Uptake of Amyloid β‐Protein by Microglia Derived from the Human Cortex

Li, Rena; Shen, Yong; Yang, Li; Lue, Lih Fen; Finch, Caleb E.; Rogers, Joseph

doi:10.1046/j.1471-4159.2000.0751447.x

Cited by 147 publications

(94 citation statements)

References 50 publications

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“…Another mechanism by which estrogen replacement therapy could impact risk of Alzheimer's disease has been reported by Rogers and colleagues (Li et al 2000). These investigators found that 17␤-estradiol significantly increased the uptake of ␤-amyloid by microglia.…”

Section: Estrogen Regulation Of ␤-Amyloid Deposition and Microglial Fmentioning

confidence: 85%

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Cellular and Molecular Mechanisms of Estrogen Regulation of Memory Function and Neuroprotection Against Alzheimer's Disease: Recent Insights and Remaining Challenges

Brinton¹

2001

Learn. Mem.

164

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This review focuses on recent advances in our knowledge of estrogen action in the brain. The greatest amount of attention was devoted to those studies that impact our understanding of estrogen regulation of memory function and prevention of degenerative diseases associated with memory systems, such as Alzheimer's disease. A review of recent advances in our understanding of estrogen receptors, both nuclear and membrane, is also presented. Finally, these data are considered in regard to their relevancy to the use of estrogen replacement therapy for cognitive health throughout menopause and the development of an estrogen replacement therapy designed for the unique requirements of the brain.The relationship between memory function and estrogen was first noted clinically as women entering menopause frequently voiced complaints of memory and concentration difficulties (Sherwin 1999). In fact, changes in cognitive functioning have long been associated with menopause (Neurgaren and Kraines 1965). The shift from observation of this phenomenon to scientific human study occurred in the mid-1980's when Sherwin and colleagues began a systematic analysis of the impact of estrogen loss and replacement on memory function (Sherwin 2000). Results of these analyses demonstrated that verbal memory declined with the loss of estrogen and was restored to premenopausal levels when estrogen replacement therapy was instituted immediately following menopause (Sherwin 1988). An earlier important discovery relevant to estrogen effects on memory function came from basic sciences studies in the mid and late 1970's by Luine and colleagues, who found that 17␤-estradiol increased choline acetyltransferase activity which led to increased acetylcholine levels (Luine 1985). Based on these findings, Fillit investigated the impact of estrogen replacement therapy on cognitive function in women with Alzheimer's disease (Fillit et al. 1986). The results of this small clinical trial proved to be pivotal and led to multiple international clinical and epidemiological studies which in turn led to an intense study of the impact of estrogen on the mechanisms of memory in both animals and humans (Brinton 1998). Presented here is a review of the more recent studies, with an emphasis on conceptually linking the many individual findings that have been generated in the past several years. In addition, an analysis of emerging data relevant to our understanding of estrogen regulation of memory function and prevention of Alzheimer's disease is presented. Estrogen-Induced Neurotrophism and Underlying MechanismsEstrogen-induced neurotrophic effects are now well documented in vitro and also in vivo preparations (Fig. 1) (ToranAllerand 1984(ToranAllerand , 2000 Brinton 1993;Murphy and Segal 1996;Brinton et al. 1997bWoolley, 1999). Investigations to determine the mechanism of estrogen-induced neurotrophism have pointed to a temporal cascade of estrogen-inducible effects that are mediated by separate but potentially interacting pathways. It also appears that blockade of ...

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Section: Estrogen Regulation Of ␤-Amyloid Deposition and Microglial Fmentioning

confidence: 85%

“…These investigators found that 17␤-estradiol significantly increased the uptake of ␤-amyloid by microglia. The expression of ER␤ was also up-regulated by estrogen treatment (Li et al 2000).…”

Section: Estrogen Regulation Of ␤-Amyloid Deposition and Microglial Fmentioning

confidence: 93%

Cellular and Molecular Mechanisms of Estrogen Regulation of Memory Function and Neuroprotection Against Alzheimer's Disease: Recent Insights and Remaining Challenges

Brinton¹

2001

Learn. Mem.

164

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“…Estradiol increases APP expression in neuronal cells ( [35,109,256]) and reduces Ab peptide production while enhancing its clearance ( [36,137,256]). A modification of Ab levels was induced by estradiol treatment in the Tg2576 AD model [267].…”

Section: Estrogens and Alzheimer's Diseasementioning

confidence: 99%

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Vegeto

Benedusi

Maggi

2008

Frontiers in Neuroendocrinology

278

206

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a b s t r a c tRecent studies highlight the prominent role played by estrogens in protecting the central nervous system (CNS) against the noxious consequences of a chronic inflammatory reaction. The neurodegenerative process of several CNS diseases, including Multiple Sclerosis, Alzheimer's and Parkinson's Diseases, is associated with the activation of microglia cells, which drive the resident inflammatory response. Chronically stimulated during neurodegeneration, microglia cells are thought to provide detrimental effects on surrounding neurons. The inhibitory activity of estrogens on neuroinflammation and specifically on microglia might thus be considered as a beneficial therapeutic opportunity for delaying the onset or progression of neurodegenerative diseases; in addition, understanding the peculiar activity of this female hormone on inflammatory signalling pathways will possibly lead to the development of selected anti-inflammatory molecules. This review summarises the evidence for the involvement of microglia in neuroinflammation and the anti-inflammatory activity played by estrogens specifically in microglia.

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“…Estrogen deficiency accelerated the formation of Amyloid plaque in mice (Yue et al, 2005). Estrogen treatment reduced the level of Amyloid (Jaffe et al, 1994;Xu et al, 1998) and its availability through enhancing the uptake of Amyloid by microglia (R. Li et al, 2000). In vitro estrogen treatment inhibited the formation of toxic Amyloid oligomers (Morinaga et al, 2007).…”

Section: Amyloid βmentioning

confidence: 99%

Estrogen and Brain Protection

Ju¹,

Metzger²,

Jung³

2012

Sex Steroids

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Estrogen Enhances Uptake of Amyloid β‐Protein by Microglia Derived from the Human Cortex

Cited by 147 publications

References 50 publications

Cellular and Molecular Mechanisms of Estrogen Regulation of Memory Function and Neuroprotection Against Alzheimer's Disease: Recent Insights and Remaining Challenges

Cellular and Molecular Mechanisms of Estrogen Regulation of Memory Function and Neuroprotection Against Alzheimer's Disease: Recent Insights and Remaining Challenges

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Estrogen and Brain Protection

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