Rapid actions of oestrogens and their receptors on memory acquisition and consolidation in females

Sheppard, Paul A. S.; Koss, Wendy A.; Frick, Karyn M.; Choleris, Elena

doi:10.1111/jne.12485

Cited by 47 publications

(38 citation statements)

References 95 publications

(340 reference statements)

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“…These non-genomic mechanisms promote the rapid activation of different intracellular signaling pathways that ultimately may lead to neuroprotection. The best characterized pathway in neurons involves the activation of extracellular signal-regulated kinases (ERK) and phosphotidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase 3 (GSK3) pathway in brain areas related to memory and cognition (Kelly and Levin, 2001 ; Marin et al, 2005 ; Garcia-Segura et al, 2006 ; Sheppard et al, 2017 ). In septal and hippocampal neurons, activation of PI3K/Akt/GSK3 signal transduction has been shown to protect against injuries induced by, Aβ exposure, glutamate exocytosis, staurosporine-induced apoptosis, and oxygen glucose deprivation (Marin et al, 2005 ; Zhao et al, 2016 ).…”

Section: Multifactorial Roles Of Estrogen Receptors In Brain Preservamentioning

confidence: 99%

Estrogen Interactions With Lipid Rafts Related to Neuroprotection. Impact of Brain Ageing and Menopause

Marín

Dı́az

2018

Front. Neurosci.

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Estrogens (E2) exert a plethora of neuroprotective actions against aged-associated brain diseases, including Alzheimer's disease (AD). Part of these actions takes place through binding to estrogen receptors (ER) embedded in signalosomes, where numerous signaling proteins are clustered. Signalosomes are preferentially located in lipid rafts which are dynamic membrane microstructures characterized by a peculiar lipid composition enriched in gangliosides, saturated fatty acids, cholesterol, and sphingolipids. Rapid E2 interactions with ER-related signalosomes appear to trigger intracellular signaling ultimately leading to the activation of molecular mechanisms against AD. We have previously observed that the reduction of E2 blood levels occurring during menopause induced disruption of ER-signalosomes at frontal cortical brain areas. These molecular changes may reduce neuronal protection activities, as similar ER signalosome derangements were observed in AD brains. The molecular impairments may be associated with changes in the lipid composition of lipid rafts observed in neurons during menopause and AD. These evidences indicate that the changes in lipid raft structure during aging may be at the basis of alterations in the activity of ER and other neuroprotective proteins integrated in these membrane microstructures. Moreover, E2 is a homeostatic modulator of lipid rafts. Recent work has pointed to this relevant aspect of E2 activity to preserve brain integrity, through mechanisms affecting lipid uptake and local biosynthesis in the brain. Some evidences have demonstrated that estrogens and the docosahexaenoic acid (DHA) exert synergistic effects to stabilize brain lipid matrix. DHA is essential to enhance molecular fluidity at the plasma membrane, promoting functional macromolecular interactions in signaling platforms. In support of this, DHA detriment in neuronal lipid rafts has been associated with the most common age-associated neuropathologies, namely AD and Parkinson disease. Altogether, these findings indicate that E2 may participate in brain preservation through a dual membrane-related mechanism. On the one hand, E2 interacting with ER related signalosomes may protect against neurotoxic insults. On the other hand, E2 may exert lipostatic actions to preserve lipid balance in neuronal membrane microdomains. The different aspects of the emerging multifunctional role of estrogens in membrane-related signalosomes will be discussed in this review.

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Section: Multifactorial Roles Of Estrogen Receptors In Brain Preservamentioning

confidence: 99%

Estrogen Interactions With Lipid Rafts Related to Neuroprotection. Impact of Brain Ageing and Menopause

Marín

Dı́az

2018

Front. Neurosci.

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“…Oestrogens were found to play a role in neuronal plasticity and spine synapse formation . Furthermore, many studies have shown positive effects of oestrogens on cognition . In Alzheimer's disease, oestrogens have been shown to protect neurones against the toxicity of amyloid plaques .…”

Section: Sex Steroid Hormones and Brain Functionmentioning

confidence: 99%

“…25,26 Furthermore, many studies have shown positive effects of oestrogens on cognition. [27][28][29] In Alzheimer's disease, oestrogens have been shown to protect neurones against the toxicity of amyloid plaques. 30 Nevertheless, more studies are necessary 31 because investigators from the Women's Health Initiative Memory Study found that therapy with a combination of oestrogen and progestin increased the risk for dementia in postmenopausal women and did not improve their performance in mild cognitive tasks.…”

Section: Sex Steroid Hormones and Brain Functionmentioning

confidence: 99%

Sex steroid hormones and brain function:PETimaging as a tool for research

Moraga-Amaro

Waarde

Doorduin

et al. 2018

J Neuroendocrinology

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Sex steroid hormones are major regulators of sexual characteristic among species. These hormones, however, are also produced in the brain. Steroidal hormone-mediated signalling via the corresponding hormone receptors can influence brain function at the cellular level and thus affect behaviour and higher brain functions. Altered steroid hormone signalling has been associated with psychiatric disorders, such as anxiety and depression.Neurosteroids are also considered to have a neuroprotective effect in neurodegenerative diseases. So far, the role of steroid hormone receptors in physiological and pathological conditions has mainly been investigated post mortem on animal or human brain tissues. To study the dynamic interplay between sex steroids, their receptors, brain function and behaviour in psychiatric and neurological disorders in a longitudinal manner, however, noninvasive techniques are needed. Positron emission tomography (PET) is a non-invasive imaging tool that is used to quantitatively investigate a variety of physiological and biochemical parameters in vivo. PET uses radiotracers aimed at a specific target (eg, receptor, enzyme, transporter) to visualise the processes of interest. In this review, we discuss the current status of the use of PET imaging for studying sex steroid hormones in the brain. So far, PET has mainly been investigated as a tool to measure (changes in) sex hormone receptor expression in the brain, to measure a key enzyme in the steroid synthesis pathway (aromatase) and to evaluate the effects of hormonal treatment by imaging specific downstream processes in the brain. Although validated radiotracers for a number of targets are still warranted, PET can already be a useful technique for steroid hormone research and facilitate the translation of interesting findings in animal studies to clinical trials in patients. K E Y W O R D Sandrogen receptor, neuroimaging, oestrogen receptor, positron emission tomography, sex steroid hormones | INTRODUCTIONSex steroid hormones are a family of steroidal hormones that can be divided into 3 classes: oestrogens, progestins and androgens. These hormones are major regulators of sexual functions, including the reproductive cycle, reproductive physiology and the development of accessory reproductive organs.1 However, our vision of the function of these hormones has been expanded because they not only regulate sexual behaviour, but also affect brain functions, such as memory, 2 anxiety-related behaviour 3 and other functions at the cellular level. 4 Sex steroid hormones are mainly synthesised by the ovaries and testis. The hypothalamic-pituitary-gonadal (HPG) axis is the main system by which the production and release of sex steroids is regulated. 5 Circulating sex hormones can stimulate the release ofThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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“…Recent evidence from PELP1 forebrain‐specific knockout mice demonstrated a critical role of PELP1 in mediating both extranuclear and nuclear ER signalling in the brain, as well as 17β‐oestradiol‐induced neuroprotection, anti‐inflammatory effects and regulation of cognitive function . The review by Sheppard et al examines recent developments in the study of the rapid effects of 17β‐oestradiol and ER agonists on learning and memory tasks in female rodents, including the activation of intracellular signalling cascades and epigenetic processes.…”

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confidence: 99%

“…Recent evidence from PELP1 forebrain-specific knockout mice demonstrated a critical role of PELP1 in mediating both extranuclear and nuclear ER signalling in the brain, as well as 17β-oestradiol-induced neuroprotection, anti-inflammatory effects and regulation of cognitive function 18. The review by Sheppard et al19 examines recent developments in the study of the rapid effects of 17β-oestradiol and ER agonists on learning and memory tasks in female rodents, including the activation of intracellular signalling cascades and epigenetic processes.The rapid nongenomic modulation of dendritic spinogenesis in rat and mouse hippocampal slices is mediated by sex steroids, including dihydrotestosterone, testosterone, oestradiol and progesterone.These rapid synaptic modulations are mediated by sex steroid receptors, including rapid nongenomic effects. In the review by Murakami et al,20 the results from the optical imaging of dendritic spines are discussed, together with results obtained from other types of imaging techniques, including electron microscopic imaging.Relationships between spine modulation and the modulation of cognition are also discussed.…”

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confidence: 99%