Estrogens, Aging, and Working Memory

Hampson, Elizabeth

doi:10.1007/s11920-018-0972-1

Cited by 44 publications

(27 citation statements)

References 81 publications

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“… 18 , 19 The regulation of cognitive function by estrogen is usually associated with the activation of the prefrontal cortex, which regulates the activation of cognition-related regions in the cerebral cortex. 20 , 21 In this study, we found that the ALFF value of the left gyrus rectus was increased, whereas that of the left inferior frontal gyrus was decreased in perimenopausal women. Moreover, the GMV value of the left gyrus rectus was decreased, and this may be a potential cause of changing emotions in perimenopausal women.…”

Section: Discussionsupporting

confidence: 49%

Brain functional changes in perimenopausal women: an amplitude of low-frequency fluctuation study

et al. 2021

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Objective: To evaluate the effects of sex hormones on amplitude of low-frequency fluctuation (ALFF) in brain regions related to cognition in perimenopausal women. Methods: This cross-sectional study involved 25 perimenopausal women and 25 premenopausal women who underwent behavioral evaluations, sex hormone level measurements, and functional magnetic resonance imaging (fMRI). All data and ALFF analyses were preprocessed using the Data Processing Assistant for Resting-State fMRI. Statistical analyses were performed using the Resting-State fMRI Data Analysis Toolkit to explore the differences in ALFF between perimenopausal and premenopausal women. The gray matter volume (GMV) values extracted from brain regions (regions of interest) with significantly different ALFF values between the perimenopausal and premenopausal groups were compared. We analyzed the correlations of the ALFF and GMV values of these regions of interest with the results of behavioral evaluations and sex hormone levels in the two groups. Results: Compared with the premenopausal group, the perimenopausal group showed significant ALFF increase in the left gyrus rectus. Regions with decreased ALFF in the perimenopausal group included the left superior temporal gyrus, left inferior frontal gyrus, and left insula. The GMV values of the left gyrus rectus and left superior temporal gyrus were reduced in perimenopausal women. Furthermore, the estradiol level was negatively correlated with the ALFF value of the left gyrus rectus in perimenopausal women. Conclusions: The ALFF and GMV values of certain brain regions related to cognitive function were changed in perimenopausal women. Such functional brain alterations may provide more information regarding the mechanism of cognitive dysfunction in perimenopausal women.

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Section: Discussionsupporting

confidence: 49%

Brain functional changes in perimenopausal women: an amplitude of low-frequency fluctuation study

et al. 2021

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“…It is now accepted that ovariectomized (OVX) adult rodents share common features with aged animals regarding brain function, including changes in mitochondrial function, synaptic plasticity, behavior and cognition (Zárate et al, 2017b). To characterize our animal model of surgical menopause in adult Wistar rats at the behavioral level, we assessed parameters of spatial working memory, anxiety and depression, which are known to be modulated by ovarian hormones (Diz-Chaves et al, 2012; Kiss et al, 2012; Cao et al, 2013; Rodríguez-Landa et al, 2017; Hampson, 2018; da Silva Moreira et al, 2016). Twelve-week ovarian hormone-deprived rats showed lower spontaneous alternation behavior in the Y-maze, indicating impaired spatial working memory (Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

Humanin, a Mitochondrial-Derived Peptide Released by Astrocytes, Prevents Synapse Loss in Hippocampal Neurons

Zárate

Traetta

Codagnone

et al. 2019

Front. Aging Neurosci.

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Astroglial cells are crucial for central nervous system (CNS) homeostasis. They undergo complex morpho-functional changes during aging and in response to hormonal milieu. Ovarian hormones positively affect different astroglia parameters, including regulation of cell morphology and release of neurotrophic and neuroprotective factors. Thus, ovarian hormone loss during menopause has profound impact in astroglial pathophysilogy and has been widely associated to the process of brain aging. Humanin (HN) is a secreted mitochondrial-encoded peptide with neuroprotective effects. It is localized in several tissues with high metabolic rate and its expression decreases with age. In the brain, humanin has been found in glial cells in physiological conditions. We previously reported that surgical menopause induces hippocampal mitochondrial dysfunction that mimics an aging phenotype. However, the effect of ovarian hormone deprivation on humanin expression in this area has not been studied. Also, whether astrocytes express and release humanin and the regulation of such processes by ovarian hormones remain elusive. Although humanin has also proven to be beneficial in ameliorating cognitive impairment induced by different insults, its putative actions on structural synaptic plasticity have not been fully addressed. In a model of surgical menopause in rats, we studied hippocampal humanin expression and localization by real-time quantitative polymerase chain reaction (RT-qPCR) and double immunohistochemistry, respectively. Humanin production and release and ovarian hormone regulation of such processes were studied in cultured astrocytes by flow cytometry and ELISA, respectively. Humanin effects on glutamate-induced structural synaptic alterations were determined in primary cultures of hippocampal neurons by immunocytochemistry. Humanin expression was lower in the hippocampus of ovariectomized rats and its immunoreactivity colocalized with astroglial markers. Chronic ovariectomy also promoted the presence of less complex astrocytes in this area. Ovarian hormones increased humanin intracellular content and release by cultured astrocytes. Humanin prevented glutamate-induced dendritic atrophy and reduction in puncta number and total puncta area for pre-synaptic marker synaptophysin in cultured hippocampal neurons. In conclusion, astroglial functional and morphological alterations induced by chronic ovariectomy resemble an aging phenotype and could affect astroglial support to neuronal function by altering synaptic connectivity and functionality. Reduced astroglial-derived humanin may represent an underlying mechanism for synaptic dysfunction and cognitive decline after menopause.

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“…Extensive reports suggest the particular involvement of estrogen on the working memory [ 86 , 87 ]. In an ovariectomy performed on rodents, both spatial and nonspatial working memory deficits were observed, and the estradiol treatment also rescued those deficits [ 88 ].…”

Section: Estrogen Receptor Signalingmentioning

confidence: 99%

The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders

Hwang

Lee

Kim

et al. 2020

IJMS

112

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Increasing evidence suggests estrogen and estrogen signaling pathway disturbances across psychiatric disorders. Estrogens are not only crucial in sexual maturation and reproduction but are also highly involved in a wide range of brain functions, such as cognition, memory, neurodevelopment, and neuroplasticity. To add more, the recent findings of its neuroprotective and anti-inflammatory effects have grown interested in investigating its potential therapeutic use to psychiatric disorders. In this review, we analyze the emerging literature on estrogen receptors and psychiatric disorders in cellular, preclinical, and clinical studies. Specifically, we discuss the contribution of estrogen receptor and estrogen signaling to cognition and neuroprotection via mediating multiple neural systems, such as dopaminergic, serotonergic, and glutamatergic systems. Then, we assess their disruptions and their potential implications for pathophysiologies in psychiatric disorders. Further, in this review, current treatment strategies involving estrogen and estrogen signaling are evaluated to suggest a future direction in identifying novel treatment strategies in psychiatric disorders.

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Estrogens, Aging, and Working Memory

Cited by 44 publications

References 81 publications

Brain functional changes in perimenopausal women: an amplitude of low-frequency fluctuation study

Brain functional changes in perimenopausal women: an amplitude of low-frequency fluctuation study

Humanin, a Mitochondrial-Derived Peptide Released by Astrocytes, Prevents Synapse Loss in Hippocampal Neurons

The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders

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