New roles for neuronal estrogen receptors

Lu, Ching–Liang; Herndon, Charles

doi:10.1111/nmo.13121

Cited by 42 publications

(31 citation statements)

References 68 publications

(122 reference statements)

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“…In female rats, after tasks that involve the hippocampus, binding of an agonist to GPER strengthen their reference memory, while the binding of an antagonist inhibits the reference memory. The [45]. Another study investigated the effect of E2 on social transmission of food preferences (STFP) task in ovariectomized mice and the role of estrogen receptors in this process.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of estrogen and G protein-coupled estrogen receptor 1 (GPER) levels in drug-naïve patients with attention deficit hyperactivity disorder (ADHD)

Şahın

Altun

Kurutaş

et al. 2018

Bosn J of Basic Med Sci

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Estrogen has a crucial role in the regulation of reproductive and neuroendocrine function and exerts its effects through two classes of receptors, nuclear and membrane estrogen receptors (mERs). G protein-coupled estrogen receptor 1 (GPER) is a member of mERs, and despite limited research on the levels of GPER in patients with psychiatric diseases, a role of GPER in such conditions has been suggested. Here we evaluated serum estrogen and GPER levels in children with attention deficit hyperactivity disorder (ADHD) in relation to their age- and gender-matched healthy controls. A total of 82 children were included in the study, 47 drug- naïve patients with ADHD (age: 6-12 years; male/female: 34/13) and 35 healthy controls (age: 6-12 years; male/female: 19/16). The subgroups according to ADHD types were inattentive, hyperactive/impulsive, and combined. Serum estrogen was measured using an immunoassay system, while serum GPER was determined using a commercial sandwich enzyme-linked immunosorbent assay kit. Estrogen levels in children with ADHD were similar as in control group, while GPER levels were significantly lower in ADHD group compared to controls (p < 0.05). Logistic regression analysis showed a significant association between GPER levels and ADHD (p < 0.05), and no association between estrogen levels and ADHD (p > 0.05). No significant differences were found in GPER and estrogen levels between ADHD subgroups (p > 0.05). To the best of our knowledge, this study is the first to investigate estrogen and GPER levels in ADHD. Our preliminary findings suggest a relationship between serum GPER levels and ADHD, and this should be further investigated.

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Section: Discussionmentioning

confidence: 99%

Evaluation of estrogen and G protein-coupled estrogen receptor 1 (GPER) levels in drug-naïve patients with attention deficit hyperactivity disorder (ADHD)

Şahın

Altun

Kurutaş

et al. 2018

Bosn J of Basic Med Sci

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“…Even though some of these actions may be explained by the intrinsic antioxidant properties of this hormone, acting as free radical scavenger of oxidative stress (Prokai et al, 2003 ), the majority of E2 neuroprotective effects require binding to ERs. To date, three distinct ERs have been characterized distinctly distributed throughout the different brain areas: ERα, ERβ, and G-protein coupled ER1 (GPER) (Prossintz and Barton, 2011 ; Lu and Herndon, 2017 ). In addition, a variety of splice variants of ERα and ERβ (ranging from 36 to 80 kDa) has also been identified in different systems, although its functional relevance in brain preservation is still unclear (Ascenzi et al, 2006 ; Marin et al, 2006 ; Kim et al, 2017 ).…”

Section: General Overviewmentioning

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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“…Other neuronal functions in which activation of GPER has been linked to positive outcomes include depression, pain, metabolic regulation (body weight, energy balance), and post ischemic stroke (62). Since most of the neurological studies have focused on targeting GPER per se, and because GPER-specific agonists and antagonists are permeable, it is unclear whether the observed neuronal effects are due to cell surface and/or intracellular GPER.…”

Section: Introductionmentioning

confidence: 99%

Intracellular GPCRs Play Key Roles in Synaptic Plasticity

Jong

Harmon

O’Malley

2018

ACS Chem. Neurosci.

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The trillions of synaptic connections within the human brain are shaped by experience and neuronal activity both of which underlie synaptic plasticity and ultimately learning and memory. G protein-coupled receptors (GPCRs) play key roles in synaptic plasticity by strengthening or weakening synapses and/or shaping dendritic spines. While most studies of synaptic plasticity have focused on cell surface receptors and their downstream signaling partners, emerging data point to a critical new role for the very same receptors to signal from inside the cell. Intracellular receptors have been localized to nuclear, endoplasmic reticulum, lysosomes and mitochondria. From these intracellular positions, such receptors may couple to different signaling systems, display unique desensitization patterns and/or show distinct patterns of subcellular distribution. Intracellular GPCRs can be activated at the cell surface, endocytosed and transported to an intracellular site or simply activated in situ by de novo ligand synthesis, diffusion of permeable ligands or active transport of nonpermeable ligands. Current findings reinforce the notion that intracellular GPCRs play a dynamic role in synaptic plasticity and learning and memory. As new intracellular GPCR roles are defined, the need to selectively tailor agonists and/or antagonists to both intracellular and cell surface receptors may lead to the development of more effective therapeutic tools.

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New roles for neuronal estrogen receptors

Cited by 42 publications

References 68 publications

Evaluation of estrogen and G protein-coupled estrogen receptor 1 (GPER) levels in drug-naïve patients with attention deficit hyperactivity disorder (ADHD)

Evaluation of estrogen and G protein-coupled estrogen receptor 1 (GPER) levels in drug-naïve patients with attention deficit hyperactivity disorder (ADHD)

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

Intracellular GPCRs Play Key Roles in Synaptic Plasticity

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