Sex hormones and proteins involved in brain plasticity

Piña-Medina, Ana Gabriela; Bello-Álvarez, Claudia; Zamora-Sánchez, Carmen J.

doi:10.1016/bs.vh.2020.04.002

Cited by 11 publications

(8 citation statements)

References 108 publications

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“…Our lack of significant associations on the X-chromosome suggests that X-chromosomal loci from previous investigations confer a more global effect on neuroticism with no heterogeneity across sex. The lack of X-chromosome association may suggest that sex differences in neuroticism arise because of neurodevelopmental and/or neuroplastic effects of sex steroids (45). As a transdiagnostic feature of disorders with internalizing symptoms, we might hypothesize that X-chromosomal susceptibility loci for PTSD, MDD, and GAD may have similar global effects with few sex-specific effects (46).…”

Section: Discussionmentioning

confidence: 99%

Sex-specific genetic and transcriptomic liability to neuroticism

Wendt

Pathak

Singh

et al. 2022

Preprint

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Background: The presentation, etiology, and relative risk of psychiatric disorders are strongly influenced by biological sex. Neuroticism is a transdiagnostic feature of psychiatric disorders displaying prominent sex differences. We performed genome-wide association studies (GWAS) of neuroticism separately in males and females to identify sex-specific genetic and transcriptomic profiles. Methods: Neuroticism scores were derived from the Eysenck Personality Inventory Neuroticism scale. GWAS were performed in 145,669 females and 129,229 males from the UK Biobank considering autosomal and X-chromosomal variation. Two-sided Z-tests were used to test for sex-specific effects of discovered loci, genetic correlates (N=673 traits), tissue and gene transcriptomic profiles, and polygenic associations across health outcomes in the Vanderbilt University Biobank (BioVu, 39,692 females and 31,268 males). Results: The SNP-heritability of neuroticism was not statistically different between males (h2=10.6%) and females (h2=11.85%). Four female-specific (rs10736549-CNTN5, rs6507056-ASXL3, rs2087182-MMS22L, and rs72995548-HSPB2) and two male-specific (rs10507274-MED13L and rs7984597) neuroticism risk loci reached genome-wide significance. Male- and female-specific neuroticism polygenic scores were most significantly associated with mood disorders (male OR=1.11, P=1.40x10-9; female OR=1.14, P=6.05x10-22). They also associated with sex-specific laboratory measures related to erythrocyte count, distribution, and hemoglobin concentration. Gene expression variation in the pituitary was enriched for neuroticism loci in males (males β=0.026, P=0.002) and genetically-regulated transcriptomic changes highlighted the effect of RAB7L1, TEX26, and PLOT1.

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Section: Discussionmentioning

confidence: 99%

Sex-specific genetic and transcriptomic liability to neuroticism

Wendt

Pathak

Singh

et al. 2022

Preprint

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“…During this time the two major sex hormones: estrogen (17β estradiol in rodents) and progesterone undergo dramatic out-of-phase fluctuations in the level of secretion ( Figure 1A ). Since these lipophilic steroid molecules pass readily through the blood brain barrier, their concentration in the plasma is followed by parallel changes in concentration in the brain where both hormones are neuroactive, acting on genomic (nuclear) as well as at membrane-bound receptors, the latter leading to rapid non-genomic effects on membrane excitability ( 29 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety

2021

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Anxiety disorders are more prevalent in women than in men. In women the menstrual cycle introduces another variable; indeed, some conditions e.g., premenstrual syndrome, are menstrual cycle specific. Animal models of fear and anxiety, which form the basis for research into drug treatments, have been developed almost exclusively, using males. There remains a paucity of work using females and the available literature presents a confusing picture. One confound is the estrous cycle in females, which some authors consider, but many do not. Importantly, there are no accepted standardized criteria for defining cycle phase, which is important given the rapidly changing hormonal profile during the 4-day cycle of rodents. Moreover, since many behavioral tests that involve a learning component or that consider extinction of a previously acquired association require several days to complete; the outcome may depend on the phase of the cycle on the days of training as well as on test days. In this article we consider responsiveness of females compared to males in a number of commonly used behavioral tests of anxiety and fear that were developed in male rodents. We conclude that females perform in a qualitatively similar manner to males in most tests although there may be sex and strain differences in sensitivity. Tests based on unconditioned threatening stimuli are significantly influenced by estrous cycle phase with animals displaying increased responsiveness in the late diestrus phase of the cycle (similar to the premenstrual phase in women). Tests that utilize conditioned fear paradigms, which involve a learning component appear to be less impacted by the estrous cycle although sex and cycle-related differences in responding can still be detected. Ethologically-relevant tests appear to have more translational value in females. However, even when sex differences in behavior are not detected, the same outward behavioral response may be mediated by different brain mechanisms. In order to progress basic research in the field of female psychiatry and psychopharmacology, there is a pressing need to validate and standardize experimental protocols for using female animal models of anxiety-related states.

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“…[44][45][46][47][48][49][50] The progesterone-PR axis regulates the proliferation of neural progenitor cells, [51][52][53] sexual differentiation, and CNS tumor development. [54][55][56][57][58][59][60][61] PR activation also has neuroprotective and antiinflammatory roles in the CNS. [62][63][64] In addition, the progesterone-PR axis enhances developmental myelination through the regulation of OPC proliferation and maturation, and through increased MBP expression in the cerebellum.…”

Section: Progesterone Receptormentioning

confidence: 99%

Nuclear hormone receptors in demyelinating diseases

Veloz

McKenzie

Palacios

et al. 2022

J Neuroendocrinology

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Demyelination results from the pathological loss of myelin and is a hallmark of many neurodegenerative diseases. Despite the prevalence of demyelinating diseases, there are no disease modifying therapies that prevent the loss of myelin or promote remyelination. This review aims to summarize studies in the field that highlight the importance of nuclear hormone receptors in the promotion and maintenance of myelination and the relevance of nuclear hormone receptors as potential therapeutic targets for demyelinating diseases.These nuclear hormone receptors include the estrogen receptor, progesterone receptor, androgen receptor, vitamin D receptor, thyroid hormone receptor, peroxisome proliferator-activated receptor, liver X receptor, and retinoid X receptor. Pre-clinical studies in well-established animal models of demyelination have shown a prominent role of these nuclear hormone receptors in myelination through their promotion of oligodendrocyte maturation and development. The activation of the nuclear hormone receptors by their ligands also promotes the synthesis of myelin proteins and lipids in mouse models of demyelination. There are limited clinical studies that focus on how the activation of these nuclear hormone receptors could alleviate demyelination in patients with diseases such as multiple sclerosis (MS). However, the completed clinical trials have reported improved clinical outcome in MS patients treated with the ligands of some of these nuclear hormone receptors. Together, the positive results from both clinical and pre-clinical studies point to nuclear hormone receptors as promising therapeutic targets to counter demyelination.

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Sex hormones and proteins involved in brain plasticity

Cited by 11 publications

References 108 publications

Sex-specific genetic and transcriptomic liability to neuroticism

Sex-specific genetic and transcriptomic liability to neuroticism

Effect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety

Nuclear hormone receptors in demyelinating diseases

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