Estrogen deficiency exacerbates Aβ-induced memory impairment through enhancement of neuroinflammation, amyloidogenesis and NF-ĸB activation in ovariectomized mice

Yun, Jaesuk; Yeo, In Jun; Hwang, Chul Ju; Choi, Dong‐Young; Im, Hyung-Sik; Kim, Ji Youg; Choi, Won Rak; Jung, Myung Hun; Han, Sang‐Bae; Hong, Jin Tae

doi:10.1016/j.bbi.2018.05.013

Cited by 62 publications

(53 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is regulated by estradiol and plays a central role in the hormonal control of neuroinflammation (see Section 4.7). The regulation of NFκB activation by estradiol is one of the neuroprotective mechanisms activated by the hormone in animal models of neurodegenerative diseases, such as traumatic brain injury, cerebral ischemia and Alzheimer's disease (Wen et al, 2004;Cook et al, 2018;Yun et al, 2018; Table 2). In these models, estradiol deficiency increases brain damage in parallel with an increased NFκB activation (Cook et al, 2018;Yun et al, 2018; Table 2).…”

Section: Nfκbmentioning

confidence: 99%

Molecular mechanisms and cellular events involved in the neuroprotective actions of estradiol. Analysis of sex differences

Azcoitia

Barreto

García‐Segura

2019

Frontiers in Neuroendocrinology

View full text Add to dashboard Cite

Estradiol, either from peripheral or central origin, activates multiple molecular neuroprotective and neuroreparative responses that, being mediated by estrogen receptors or by estrogen receptor independent mechanisms, are initiated at the membrane, the cytoplasm or the cell nucleus of neural cells. Estrogen-dependent signaling regulates a variety of cellular events, such as intracellular Ca 2+ levels, mitochondrial respiratory capacity, ATP production, mitochondrial membrane potential, autophagy and apoptosis. In turn, these molecular and cellular actions of estradiol are integrated by neurons and non-neuronal cells to generate different tissue protective responses, decreasing blood-brain barrier permeability, oxidative stress, neuroinflammation and excitotoxicity and promoting synaptic plasticity, axonal growth, neurogenesis, remyelination and neuroregeneration. Recent findings indicate that the neuroprotective and neuroreparative actions of estradiol are different in males and females and further research is necessary to fully elucidate the causes for this sex difference.

show abstract

Section: Nfκbmentioning

confidence: 99%

Molecular mechanisms and cellular events involved in the neuroprotective actions of estradiol. Analysis of sex differences

Azcoitia

Barreto

García‐Segura

2019

Frontiers in Neuroendocrinology

View full text Add to dashboard Cite

show abstract

“…Additionally, activated microglia do release several soluble pro-inflammatory factors like cytokines and complement components (Block and Hong, 2005;Colton and Gilbert, 1987;Liu et al, 2002;Sawada et al, 1989). Increasingly, chronic or deregulated inflammation is being recognized as a primary contributing factor to the progression and etiology of neurodegeneration (Barrientos et al, 2019;Bonifati and Kishore, 2007;Giovannini et al, 2002;Morale et al, 2006;Yun et al, 2018) as well as other disease conditions such as like atherosclerosis (Chait et al, 2005), arthritis (Mizuno, 2006) and osteoporosis (Clowes et al, 2005;Ginaldi et al, 2005). E2 has been demonstrated as one of the sex hormones that influences the progression of varied inflammatory pathologies including cardiovascular disease, (Hodgin and Maeda, 2002;Wagner et al, 2002), osteoporosis (Turner et al, 1994;Watts, 2002) and autoimmunity (Cutolo et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…The hormone replenishment therapy has been suggested to induce an anti-inflammatory reaction (Abu-Taha et al, 2009;Vegeto et al, 2008). Estrogen has been reported to play a modulatory role in animal models of various neuroinflammatory diseases (Brown et al, 2010;Lewis et al, 2008;Mor et al, 1999;Sarvari et al, 2012;Tiwari-Woodruff et al, 2007;Vegeto et al, 2003;Yun et al, 2018). Our study aimed at determining the effect of ovariectomy & hormone replenishment on the expression of complement proteins and the observations revealed a significant difference in the complement expression in OVX and treated groups (E2 or SERM), the expression level in the later being comparable to the OVI group.…”

Section: Discussionmentioning

confidence: 99%

Preliminary Evidence of the role of estrogen and tamoxifen-induced regulation of complement proteins in rat hippocampus

Kumar

Dhar

2020

Preprint

View full text Add to dashboard Cite

Effects of Estrogen (E2) is widespread in the human body; still, an unresolved paradox.Neurodegeneration and neuroinflammation are inherently associated with age progression, debilitating by hormone deprivation, especially in female. Senescent cells accumulate with age and promote tissue deterioration in the body system. Neurodegenerative diseases drive a healthy life towards to morbidity and feebleness; despite the different etiology, uncontrolled inflammation is one of the significant causals factors. We here used post-menopausal model (ovariectomized female rat), E2 replenishment therapy reduces the expression of inflammatory mediators, such as complement proteins (C3, C1q, and C3aR) in these animals.E2 therapy could limit the ovariectomy-induced increase of inflammatory events in brain regions such as the hippocampus. Also, the duration of hormone deprivation could be a determinant for the intensity of the anti-inflammatory actions of estrogen. On the whole, considerable evidence, including that from the present study supports the view that complement biosynthesis, which plays a significant role in phagocytosis of cellular debris and synaptic pruning of postnatal neural circuits goes uncontrolled and could be the inducing factor for enhanced neurodegeneration following hormone deprivation.

show abstract

“…It can lead to secondary systemic metabolic disorders such as osteoporosis, obesity, and type 2 diabetes (Nicodemus, Folsom, & Iowa Women's Health, ; Russo et al., ; Xu, Lovre, & Mauvais‐Jarvis, ). It has been reported that chronic estrogen deficient condition has pivotally negative effects on brain functions such as enhanced oxidative stress, memory impairment, amyloidogenesis, and hyperactivation of NF‐ĸB activation (Anukulthanakorn et al., ; Connell et al., ; Riedel, Thompson, & Brinton, ; Topcuoglu et al., ; Xiao, Cao, Marshall, & Hu, ; Yun et al., ; Zhao, Woody, & Chhibber, ). Estrogen receptors are known to be present in every area of the brain.…”

Section: Introductionmentioning

confidence: 99%

“…Authors G.-H. Kim and H. K. Baek contributed equally to this work. Xiao, Cao, Marshall, & Hu, 2010;Yun et al, 2018;Zhao, Woody, & Chhibber, 2015). Estrogen receptors are known to be present in every area of the brain.…”

Section: Introductionmentioning

confidence: 99%

Chronic Oral Administration of Tenebrio molitor Extract Exhibits Inhibitory Effect on Glucocorticoid Receptor Overexpression in the Hippocampus of Ovariectomy‐Induced Estrogen Deficient Mice

Kim

Baek

Lee

et al. 2019

Journal of Food Science

View full text Add to dashboard Cite

It has been reported that estrogen deficiency in female disrupts systemic endocrinologic regulatory mechanisms, finally leading to osteoporotic condition. Estrogen deficiency also down‐regulates brain functions due to its deficits of its original roles in a number of neurological events. Therefore, it is necessary to find alternative materials that can prevent osteoporotic condition and maintain normal brain functions to correct such hormone deficiency. In the present study, we found that novel compounds originated from larvae of Tenebrio molitor (TM) possessed anti‐osteoporotic effect. They could also prevent abnormal progressive brain function by deaccelerating enhanced HPA‐axis negative feedback while maintaining neurogenesis in hippocampus. We daily administered TM to ovariectomized (OVX) ddY mice for 4 weeks and then performed histological and hormonal evaluations for its anti‐osteoporotic effects. In addition, we investigated glucocorticoid receptor (GR) expression and neuroblast expression (DCX) in the hippocampal dentate gyrus morphologically by immunohistochemistry analysis. According to our results, TM has anti‐osteoporotic effects. It also tends to bring interfered brain environment back to normal condition. These results suggest that TM might have anti‐osteoporosis effect and enhancing effects on enrichment of environment in brain by being antidestroyed hormonal deficiency simultaneously. This is the first study to report that TM can be used as source of bioactive substance to prevent decreased neurogenesis and impaired HPA axis driven by high GR expression in the hippocampus in hormonal deficient female animals. Practical Application Anti‐osteoporosis effect and stress resistance due to improved brain function caused by the ingestion of Tenebrio molitor extract were observed in postmenopausal women. T. molitor is available as a nutritional supplement for bone and brain health, which menopausal women need most.

show abstract

Estrogen deficiency exacerbates Aβ-induced memory impairment through enhancement of neuroinflammation, amyloidogenesis and NF-ĸB activation in ovariectomized mice

Cited by 62 publications

References 50 publications

Molecular mechanisms and cellular events involved in the neuroprotective actions of estradiol. Analysis of sex differences

Molecular mechanisms and cellular events involved in the neuroprotective actions of estradiol. Analysis of sex differences

Preliminary Evidence of the role of estrogen and tamoxifen-induced regulation of complement proteins in rat hippocampus

Chronic Oral Administration of Tenebrio molitor Extract Exhibits Inhibitory Effect on Glucocorticoid Receptor Overexpression in the Hippocampus of Ovariectomy‐Induced Estrogen Deficient Mice

Contact Info

Product

Resources

About