When steroids, such as pregnenolone, progesterone and oestrogen, are synthesised de novo in neural tissues, they are more specifically referred to as neurosteroids. These neurosteroids bind specific ...receptors to promote essential brain functions. Pregnenolone supports cognition and protects mouse hippocampal cells against glutamate and amyloid peptide‐induced cell death. Progesterone promotes myelination, spinogenesis, synaptogenesis, neuronal survival and dendritic growth. Allopregnanolone increases hippocampal neurogenesis, neuronal survival and cognitive functions. Oestrogens, such as oestradiol, regulate synaptic plasticity, reproductive behaviour, aggressive behaviour and learning. In addition, neurosteroids are neuroprotective in animal models of Alzheimer's disease, Parkinson's disease, brain injury and ageing. Using in situ hybridisation and/or immunohistochemistry, steroidogenic enzymes, including cytochrome P450 side‐chain cleavage, 3β‐hydroxysteroid dehydrogenase/Δ5‐Δ4 isomerase, cytochrome P450arom, steroid 5α‐reductase and 3α‐hydroxysteroid dehydrogenase, have been detected in numerous brain regions, including the hippocampus, hypothalamus and cerebral cortex. In the present review, we summarise some of the studies related to the synthesis and function of oestrogens and progestagens in the central nervous system.
Unique structural and optical properties of atomically thin two-dimensional semiconducting transition metal dichalcogenides enable in principle their efficient coupling to photonic cavities having ...the optical mode volume close to or below the diffraction limit. Recently, it has become possible to make all-dielectric nano-cavities with reduced mode volumes and negligible non-radiative losses. Here, we realise low-loss high-refractive-index dielectric gallium phosphide (GaP) nano-antennas with small mode volumes coupled to atomic mono- and bilayers of WSeFormula: see text. We observe a photoluminescence enhancement exceeding 10Formula: see text compared with WSeFormula: see text placed on planar GaP, and trace its origin to a combination of enhancement of the spontaneous emission rate, favourable modification of the photoluminescence directionality and enhanced optical excitation efficiency. A further effect of the coupling is observed in the photoluminescence polarisation dependence and in the Raman scattering signal enhancement exceeding 10Formula: see text. Our findings reveal dielectric nano-antennas as a promising platform for engineering light-matter coupling in two-dimensional semiconductors.
Abstract
Sodium appetite is a motivational state involving homeostatic behavior, seeking the ingest of salty substances after sodium loss. There is a temporal dissociation between sodium depletion ...(SD) and the appearance of sodium appetite. However, the responsible mechanisms for this delay remain poorly elucidated. In the present study, we measured the temporal changes at two and 24 h after SD in the gene expression of key elements within excitatory, inhibitory, and sensory areas implicated in the signaling pathways involved in the onset of sodium appetite. In SD rats, we observed that the expression of critical components within the brain control circuit of sodium appetite, including Angiotensin-type-1 receptor (Agtr1a), Oxytocin-(OXT-NP)-neurophysin-I, and serotonergic-(5HT)-type-2c receptor (Htr2c) were modulated by SD, regardless of time. However, we observed reduced phosphorylation of mitogen-activated protein kinases (MAPK) at the paraventricular nucleus (PVN) and increased oxytocin receptor (Oxtr) mRNA expression at the anteroventral of the third ventricle area (AV3V), at two hours after SD, when sodium appetite is inapparent. At twenty-four hours after SD, when sodium appetite is released, we observed a reduction in the mRNA expression of the transient receptor potential channel 1gene (Trpv1) and Oxtr in the AV3V and the dorsal raphe nucleus, respectively. The results indicate that SD exerts a coordinated timing effect, promoting the appearance of sodium appetite through changes in MAPK activity and lower Trpv1 channel and Oxtr expression that trigger sodium consumption to reestablish the hydroelectrolytic homeostasis.
Aromatase, which converts testosterone in estradiol, is involved in the generation of brain sex dimorphisms. Here we used the “four core genotypes” mouse model, in which the effect of gonadal sex and ...sex chromosome complement is dissociated, to determine if sex chromosomes influence the expression of brain aromatase. The brain of 16 days old XY mouse embryos showed higher aromatase expression in the stria terminalis and the anterior amygdaloid area than the brain of XX embryos, independent of gonadal sex. Furthermore, estradiol or dihydrotestosterone increased aromatase expression in cultures of anterior amygdala neurons derived from XX embryos, but not in those derived from XY embryos. This effect was also independent of gonadal sex. The expression of other steroidogenic molecules, estrogen receptor-α and androgen receptor was not influenced by sex chromosomes. In conclusion, sex chromosomes determine sex dimorphisms in aromatase expression and regulation in the developing mouse brain.
•XY and XX embryos showed different aromatase expression in the brain areas studied.•E2 or DHT increase aromatase in amygdala neuronal cultures from XX embryos only.•Gonadal sex, rather than sex chromosomes, influences the expression of ER-α and AR.•Sex chromosomes and gonadal factors interact in brain sex differentiation.
Previous studies indicate a sex chromosome complement (SCC) effect on the angiotensin II-sexually dimorphic hypertensive and bradycardic baroreflex responses. We sought to evaluate whether SCC may ...differentially modulate sexually dimorphic-induced sodium appetite and specific brain activity due to physiological stimulation of the rennin angiotensin system. For this purpose, we used the "four core genotype" mouse model, in which the effect of gonadal sex and SCC is dissociated, allowing comparisons of sexually dimorphic traits between XX and XY females as well as in XX and XY males. Gonadectomized mice were sodium depleted by furosemide (50 mg/kg) and low-sodium diet treatment; control groups were administered with vehicle and maintained on normal sodium diet. Twenty-one hours later, the mice were divided into two groups: one group was submitted to the water-2% NaCl choice intake test, while the other group was perfused and their brains subjected to the Fos-immunoreactivity (FOS-ir) procedure. Sodium depletion, regardless of SCC (XX or XY), induced a significantly lower sodium and water intake in females than in males, confirming the existence in mice of sexual dimorphism in sodium appetite and the organizational involvement of gonadal steroids. Moreover, our results demonstrate a SCC effect on induced brain FOS-ir, showing increased brain activity in XX-SCC mice at the paraventricular nucleus, nucleus of the solitary tract, and lateral parabrachial nucleus, as well as an XX-SCC augmented effect on sodium depletion-induced brain activity at two circumventricular organs, the subfornical organ and area postrema, nuclei closely involved in fluid and blood pressure homeostasis.
Abstract Although the biological activity of estrogen is generally mediated through nuclear estrogen receptors, a large body of evidence indicates that estrogen may also affect target cells upon ...binding to putative membrane estrogen receptors (mER) coupled to intracellular signaling cascades; however, no agreement has been reached on the nature and precise location of the putative estrogen receptor (ER) responsible for these rapid effects. In the present report we show that the expression of ERα is associated with the plasma membrane fraction of rat hypothalamic tissue at embryonic day 16. Moreover, our experiments extend these results to rat hypothalamic neurons in vitro showing that ERα can be detected from the cell exterior as a biotinylated cell-surface protein. We have also shown that the mERα is under regulation of estradiol, and the ERα agonist, 4,4′,4″-(4-propyl-1 H -pyrazole-1,3,5-triyl) tris phenol, induced extracellular-signal-regulated kinase signaling in a dose-dependent manner and in a time-course not compatible with genomic actions, supporting the notion of a membrane-initiated phenomenon.
GABAA receptor activation exerts trophic actions in immature neurons through depolarization of resting membrane potential. The switch to its classical hyperpolarizing role is developmentally ...regulated. Previous results suggest that a hormonally biased sex difference exists at the onset of the switch in hypothalamic neurons. The aim of this work was to evaluate sex differences in GABAA receptor function of hypothalamic neurons before brain masculinization by gonadal hormones. Hypothalamic cells were obtained from embryonic day 16 male and female rat foetuses, 2 days before the peak of testosterone production by the foetal testis, and grown in vitro for 9 days. Whole‐cell and perforated patch‐clamp recordings were carried out in order to measure several electrophysiological parameters. Our results show that there are more male than female neurons responding with depolarization to muscimol. Additionally, among cells with depolarizing responses, males have higher and longer lasting responses than females. These results highlight the relevance of differences in neural cell sex irrespective of exposure to sex hormones.
There are more male than female hypothalamic neurons responding with depolarization to muscimol at 9 days in vitro. In neurons with depolarizing responses, males have larger voltage changes and longer lasting responses than females. These sex differences in GABAAR function are independent of gonadal hormones because hypothalamic tissue has been taken from male and female embryos at E16, two days before neurons would be exposed to gonadal steroids in utero.
This study aimed to define whether sex chromosome complement (SCC) may differentially modulate sex differences in relative gene expression of basal Agtr1a, Agtr2, and Mas1 receptors at fore/hindbrain ...nuclei and at medulla/cortical kidney.
Samples were collected from gonadectomized male (XX and XY) and female (XX and XY) mice of the “four core genotypes” model. At brain level, a SCC effect at the area postrema was demonstrated. An increase in mRNA level of Agtr1a and Agtr1a/Agtr2 ratio in XY-SCC mice was associated with a decrease in Mas1 compared to XX-SCC mice. In the renal cortex, a SCC effect for Agtr2 and Mas1 was observed. Regardless of sex (male or female), XX-SCC mice expressed higher levels of mRNA Agtr2 and Mas1 than XY-SCC mice {F(1,12) = 6,126,p < 0.05; F(1,21) = 5,143,p < 0.05}. Furthermore, XX-female mice showed a significant increase in Mas1 expression compared to XY-female mice.
These results reveal a SCC modulatory effect at central and kidney level on angiotensin receptor expression, with an enhancement of the vasodilatory arm in XX-mice and an increase in the vasoconstriction arm in XY-mice, which may underlie sex differences in the regulation of arterial pressure.
•Sex chromomose complement modulates brain and kidney Angiotensin receptor gene expression.•The AP of XX-SCC mice shows an increase in the RAS vasodilatory arm expression.•The AP of XY-SCC mice shows an increase in the RAS vasoconstrictor arm expression.•The renal cortex of XX-SCC mice shows a shift of the RAS balance to the depressor arm.•SCCs induces a shift in RAS vasoconstrictor/vasodilator ratio at brain and kidney level.
The organizational action of testosterone during critical periods of development is the cause of numerous sex differences in the brain. However, sex differences in neuritogenesis have been detected ...in primary neuronal hypothalamic cultures prepared before the peak of testosterone production by fetal testis. In the present study we assessed the hypothesis of that cell-autonomous action of sex chromosomes can differentially regulate the expression of the neuritogenic gene neurogenin 3 (Ngn3) in male and female hypothalamic neurons, generating sex differences in neuronal development. Neuronal cultures were prepared from male and female E14 mouse hypothalami, before the fetal peak of testosterone. Female neurons showed enhanced neuritogenesis and higher expression of Ngn3 than male neurons. The silencing of Ngn3 abolished sex differences in neuritogenesis, decreasing the differentiation of female neurons. The sex difference in Ngn3 expression was determined by sex chromosomes, as demonstrated using the four core genotypes mouse model, in which a spontaneous deletion of the testis-determining gene Sry from the Y chromosome was combined with the insertion of the Sry gene onto an autosome. In addition, the expression of Ngn3, which is also known to mediate the neuritogenic actions of estradiol, was increased in the cultures treated with the hormone, but only in those from male embryos. Furthermore, the hormone reversed the sex differences in neuritogenesis promoting the differentiation of male neurons. These findings indicate that Ngn3 mediates both cell-autonomous actions of sex chromosomes and hormonal effects on neuritogenesis.
We demonstrate the emission of photons from a single molecule into a hybrid gap plasmon waveguide. Crystals of anthracene, doped with dibenzoterrylene (DBT), are grown on top of the waveguides. We ...investigate a single DBT molecule coupled to the plasmonic region of one of the guides and determine its in-plane orientation, excited state lifetime, and saturation intensity. The molecule emits light into the guide, which is remotely out-coupled by a grating. The second-order autocorrelation and cross-correlation functions show that the emitter is a single molecule and that the light emerging from the grating comes from that molecule. The coupling efficiency is found to be βWG = 11.6(1.5)%. This type of structure is promising for building new functionality into quantum-photonic circuits, where localized regions of strong emitter-guide coupling can be interconnected by low-loss dielectric guides.
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