Endogenous estradiol is associated with verbal memory in nondemented older men

Zimmerman, Molly E.; Lipton, Richard B.; Santoro, Nanette; McConnell, Daniel S.; Derby, Carol A.; Katz, Mindy J.; Baigi, Khosrow; Saunders‐Pullman, Rachel

doi:10.1016/j.bandc.2011.01.011

Cited by 24 publications

(34 citation statements)

References 57 publications

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“…Supporting this, DS females experience early-onset menopause, and bioavailable estradiol levels correlate with age of onset of AD in DS females and decreased cognitive ability in nondemented aged disomic males (89, 90, 101). In Ts65Dn female mice, chronic treatment with estrogen has been shown to increase ChAT-positive BFCN size and neurotrophic levels in the MS, modify dendritic markers and acetylcholinesterase levels in the hippocampus, and improve learning in mice between 9 and 15 months (34, 35).…”

Section: Discussionmentioning

confidence: 71%

Sex Differences in the Cholinergic Basal Forebrain in the Ts65Dn Mouse Model of Down Syndrome and Alzheimer's Disease

et al. 2013

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In the Down syndrome (DS) population, there is an early incidence of dementia and neuropathology similar to that seen in sporadic Alzheimer’s disease (AD), including dysfunction of the basal forebrain cholinergic neuron (BFCN) system. Using Ts65Dn mice, a model of DS and AD, we examined differences in the BFCN system between male and female segmentally trisomic (Ts65Dn) and disomic (2N) mice at ages 5–8 months. Quantitative stereology was applied to BFCN subfields immunolabeled for choline acetyltransferase (ChAT) within the medial septum/vertical limb of the diagonal band (MS/VDB), horizontal limb of the diagonal band (HDB) and nucleus basalis of Meynert/ substantia innominata (NBM/SI). We found no sex differences in neuron number or subregion area measurement in the MS/VDB or HDB. However, 2N and Ts65Dn females showed an average 34% decrease in BFCN number and an average 20% smaller NBM/SI region area compared with genotype-matched males. Further, relative to genotype-matched males, female mice had smaller BFCNs in all subregions. These findings demonstrate that differences between the sexes in BFCNs of young adult Ts65Dn and 2N mice are region and genotype specific. In addition, changes in post-processing tissue thickness suggest altered parenchymal characteristics between male and female Ts65Dn mice.

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Section: Discussionmentioning

confidence: 71%

Sex Differences in the Cholinergic Basal Forebrain in the Ts65Dn Mouse Model of Down Syndrome and Alzheimer's Disease

et al. 2013

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“…For example, estradiol levels in men have been positively associated with episodic memory performance, at times in the absence of significant testosterone effects (Cherrier et al, 2005; Zimmerman et al, 2011). Given that estradiol is a derivative of testosterone, such findings suggest that it may not be the level of testosterone per se, but the degree to which it is aromatized into estradiol that is most relevant to cognition.…”

Section: Discussionmentioning

confidence: 99%

Interaction of APOE genotype and testosterone on episodic memory in middle-aged men

Panizzon

Hauger

Xian

et al. 2014

Neurobiology of Aging

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Age-related changes in testosterone are believed to be a key component of the processes that contribute to cognitive aging in men. The APOE-ε4 allele may interact with testosterone and moderate the hormone’s association with cognition. The goals of the present study were to examine the degree to which free testosterone is associated with episodic memory in a community-based sample of middle-aged men, and examine the potential interaction between free testosterone and the APOE-ε4 allele. Data were utilized from 717 participants in the Vietnam Era Twin Study of Aging (VETSA). Average age was 55.4 years (SD = 2.5). Significant positive associations were observed between free testosterone level and verbal episodic memory, as well as a significant interaction between free testosterone and APOE-ε4 status. In ε4 carriers free testosterone was positively associated with verbal episodic memory performance (story recall), whereas no association was observed in ε4 non-carriers. Results support the hypothesis that APOE-ε4 status increases susceptibility to other risk factors, such as low testosterone, which may ultimately contribute to cognitive decline or dementia.

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“…Our review identified cross-sectional epidemiological studies that assessed the effects of endogenous estrogen on brain health [28,29,30,31,32]. Four of the studies examined the relationship between endogenous estrogen and memory performance [28,30,31,32] and one study examined the relationship between age of Parkinson’s disease (PD) onset and exposure to endogenous estrogen [29].…”

Section: Epidemiologic and Experimental Evidence Of Brain Health Dmentioning

confidence: 99%

“…Four of the studies examined the relationship between endogenous estrogen and memory performance [28,30,31,32] and one study examined the relationship between age of Parkinson’s disease (PD) onset and exposure to endogenous estrogen [29]. One study examined the effects of endogenous estrogens in males [32], and the other four studies examined the effects on females [28,29,30,31]. …”

Section: Epidemiologic and Experimental Evidence Of Brain Health Dmentioning

confidence: 99%

“…However, a study by Heys et al, found significant associations between proxies of endogenous estrogen exposure and cognitive delayed recall scores ( p -value = 0.001, 95% CI, 0.008–0.02) and the mini-mental state exam scores ( p -value < 0.001, 95% CI, 0.004–0.007) in a cross-sectional study of 11,094 postmenopausal women [30]. In a cross-sectional study of 181 older men, examining the effects of endogenous estrogen exposure from serum levels and verbal memory assessment scores in men, higher total levels of estradiol were associated with better performance (β = 0.17, p -value < 0.02) [32]. Cereda et al, found that age of PD onset was positively associated with the duration of exposure to endogenous estrogens using reproductive surrogates of endogenous estrogen exposure (7.10, [3.31], p -value = 0.032) in a cross-sectional study of 579 females [29].…”

Section: Epidemiologic and Experimental Evidence Of Brain Health Dmentioning

confidence: 99%

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Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

Preciados

Yoo

Roy

2016

IJMS

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During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss the brain health effects associated from exposure to EEDs including the promotion of neurodegeneration, protection against neurodegeneration, and involvement in various neurological deficits; changes in rearing behavior, locomotion, anxiety, learning difficulties, memory issues, and neuronal abnormalities. The effects of EEDs on the brain are varied during the entire life span and far-reaching with many different mechanisms. To understand endocrine disrupting chemicals mechanisms, we use bioinformatics, molecular, and epidemiologic approaches. Through those approaches, we learn how the effects of EEDs on the brain go beyond known mechanism to disrupt the circulatory and neural estrogen function and estrogen-mediated signaling. Effects on EEDs-modified estrogen and nuclear respiratory factor 1 (NRF1) signaling genes with exposure to natural estrogen, pharmacological estrogen-ethinyl estradiol, PCBs, phthalates, BPA, and metalloestrogens are presented here. Bioinformatics analysis of gene-EEDs interactions and brain disease associations identified hundreds of genes that were altered by exposure to estrogen, phthalate, PCBs, BPA or metalloestrogens. Many genes modified by EEDs are common targets of both 17 β-estradiol (E2) and NRF1. Some of these genes are involved with brain diseases, such as Alzheimer’s Disease (AD), Parkinson’s Disease, Huntington’s Disease, Amyotrophic Lateral Sclerosis, Autism Spectrum Disorder, and Brain Neoplasms. For example, the search of enriched pathways showed that top ten E2 interacting genes in AD—APOE, APP, ATP5A1, CALM1, CASP3, GSK3B, IL1B, MAPT, PSEN2 and TNF—underlie the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) AD pathway. With AD, the six E2-responsive genes are NRF1 target genes: APBB2, DPYSL2, EIF2S1, ENO1, MAPT, and PAXIP1. These genes are also responsive to the following EEDs: ethinyl estradiol (APBB2, DPYSL2, EIF2S1, ENO1, MAPT, and PAXIP1), BPA (APBB2, EIF2S1, ENO1, MAPT, and PAXIP1), dibutyl phthalate (DPYSL2, EIF2S1, and ENO1), diethylhexyl phthalate (DPYSL2 and MAPT). To validate findings from Comparative Toxicogenomics Database (CTD) curated data, we used Bayesian network (BN) analysis on microarray data of AD patients. We observed that both gender and NRF1 were associated with AD. The female NRF1 gene network is completely ...

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Endogenous estradiol is associated with verbal memory in nondemented older men

Cited by 24 publications

References 57 publications

Sex Differences in the Cholinergic Basal Forebrain in the Ts65Dn Mouse Model of Down Syndrome and Alzheimer's Disease

Sex Differences in the Cholinergic Basal Forebrain in the Ts65Dn Mouse Model of Down Syndrome and Alzheimer's Disease

Interaction of APOE genotype and testosterone on episodic memory in middle-aged men

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

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