Search Results (84)

Prolactin is a hormone with demonstrated roles in the brain, including neurogenesis, neuroprotection, learning, stress response or memory consolidation. To determine the prolactin expression in the rat hippocampus during aging and to resolve some controversies related to the presence of prolactin in the hippocampus, the aim of this study was to analyze whether changes occur in the expression of prolactin during different stages of life. To determine this, we designed an experimental study in which we analyzed the expression and location of prolactin in the rat hippocampus, Ammon’s horn and Dentate Gyrus, during different stages of life (prepubertal, postpubertal, young adult, adult and old) and checked if there are differences related to sex. Overall, the results obtained show that prolactin is present in the rat hippocampus and that prolactin is synthesized, as deduced from the findings obtained via ELISA, immunohistochemistry, qPCR and in situ hybridization. After analyzing the correlation between serum and hippocampal prolactin levels and comparing the amounts of Prl mRNA and the hormone, the results obtained suggest that hippocampal prolactin has a dual origin: local synthesis of the hormone and its passage from the blood. On the other hand, the amounts of prolactin and its mRNA in the hippocampus vary with sex and age, suggesting the existence of age-related sexual dimorphism. The results obtained suggest that hippocampal aging is related to a decrease in the hippocampal prolactin system, which helps to better understand brain aging. Full article

Since the initial report indicating that LPA₁ signaling plays a key role in initiating nerve injury-induced neuropathic pain (NeuP), subsequent studies using knockout mice and LPA_1/3 antagonists have demonstrated that LPA₁ and LPA₃ signaling impact NeuP and fibromyalgia (FM) models. In the present study, we identified hyperalgesia sexual dimorphism involving LPA_1/3 signaling in the intermittent psychological stress induced-related FM-like model called intermittent psychological stress (IPS)-induced generalized pain (IPGP) model where the hyperalgesia in IPGP mice was abolished in LPA₁- and LPA₃-knock-out mice. Pharmacological intervention by intraperitoneal (i.p.) treatments with the LPA_1/3 antagonist Ki16425 consistently prevented hyperalgesia. However, intracerebroventricular treatments with Ki16425 abolished hyperalgesia in male, but not female, mice. Notably, intrathecal treatments of Ki16425 did not prevent hyperalgesia. Further studies revealed that splenocytes derived from female IPGP mice could initiate hyperalgesia via adoptive transfer in naïve mice, and this effect was abolished when donor mice were pre-treated with Ki16425 (i.p.). Thus, these studies identify male-specific LPA_1/3-mediated mechanisms in the brain underlying IPGP, as well as distinct LPA-LPA_1/3-mediated peripheral immune mechanisms. Full article

Malaria, the deadliest parasitic disease in the world, is sexually dimorphic, inflammatory, and oxidative. Males experience more severe symptoms and mortality than females do; therefore, the roles of 17β-estradiol and testosterone in this phenomenon have been studied. Both hormones affect oxidative stress, the primary mechanism of Plasmodium elimination. Estradiol has antioxidant activity, but the role of testosterone is controversial. Testosterone increases oxidative stress by reducing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities, which increase lipoperoxidation in the testis. However, the antioxidant properties of testosterone in prostate and nervous tissue have also been reported. The discrepancies are probably because when testosterone levels increase, the aromatase enzyme transforms testosterone into estrogens that possess antioxidant activity, which masks the results. Therefore, it is unknown whether testosterone is involved in the sexual dimorphism that occurs in oxidative stress in malaria. In this work, we administered testosterone and simultaneously inhibited aromatase with letrozole to evaluate the role of testosterone in the sexually dimorphic pattern of oxidative stress that occurs in the blood, spleen, and brain of male and female CBA/Ca mice infected with Plasmodium berghei ANKA (P. berghei ANKA). Testosterone triggers parasitemia in males, who also display more oxidative stress than females in the absence of infection, leading to sexually dimorphic patterns. Interestingly, increasing testosterone levels in infected mice reduced oxidative stress in males and increased oxidative stress in females, reversing or eliminating the dimorphic patterns observed. Oxidative stress varies in each tissue; the brain was the most protected, while the blood was the greatest damaged. Our findings highlight the role of testosterone as a regulator of oxidative stress in a tissue and sex-specific manner; therefore, understanding the role of testosterone in malaria may contribute to the development of sex-specific personalized antimalarial therapies. Full article

Sleepy cod (Oxyeleotris lineolata) is native to Australia and is now an economically valuable fish cultured in China and Southern Asian countries. Its growth rate exhibits as sexually dimorphic, with males generally growing more rapidly and attaining a larger body size compared to females. Thus, the effective development of sex control breeding can significantly contribute to increased yields and output value. Nevertheless, due to the lack of genomic and transcriptomic data, the molecular mechanisms underlying sex determination and gonadal differentiation in sleepy cod remain poorly understood. In this study, long-read PacBio isoform sequencing (Iso-Seq) was performed to obtain a full-length transcriptome from a pooled sample of eight tissues (kidney, brain, liver, muscle, heart, spleen, ovary and testis). A total of 30.41 G subread bases were generated and 49,113 non-redundant full-length transcripts with an average length of 2948 bp were produced. Using the full-length transcriptome as a reference, short-read Illumina sequencing was performed to investigate the differences in gene expression at the transcriptome level between ovaries and testes from 12-month-old individuals. A total of 19,102 differentially expressed transcripts (DETs) were identified, of which 8510 (44.55%) were up-regulated in the ovary and 10,592 (55.45%) were up-regulated in the testis. The DETs were mainly clustered into 241 KEGG pathways, in which oocyte meiosis and arachidonic acid metabolism were the most relevant pathways involved in gonadal differentiation. To verify the validity of the transcriptomic data, 20 DETs were selected to investigate the gonad expression profiles based on qPCR. The expression levels of all 20 screened genes were consistent with the transcriptome sequencing results. The present study provides new genetic resources—including full-length transcriptome sequences and annotation information—as a coding genomic-level reference for sleepy cod—yielding valuable insights into the genetic mechanisms of sex determination and gonadal differentiation in this economically important species. Full article

Prenatal alcohol exposure (PAE) affects around 40,000 newborns every year and poses a significant health risk. Although much is already known about the neurotoxic mechanisms of PAE, new findings continue to emerge. Studies with mouse models show that PAE leads to overexpression of proinflammatory cytokines and chemokines in the brain, which disrupts important neurodevelopmental processes such as cell migration, survival and proliferation of neurons. The chemokine CXCL16 is overexpressed in the brain following various impairments, including PAE. This study shows that CXCL16 expression varies by developmental stage and sex, consistent with known sexual dimorphism in immune responses. In females, CXCL16 expression may be influenced by estrogen-related mechanisms, possibly related to the alcohol-mediated rebound effect described here. In contrast, the male hippocampus shows greater resilience to PAE-induced CXCL16 changes. Furthermore, the presence of CXCL16 in neuronal nuclei suggests a role in gene regulation, similar to other chemokines such as CCL5 and CXCL4. These findings shed light on the role of chemokines in hippocampal neuroplasticity and may pave the way for better treatment of fetal alcohol spectrum disorder (FASD). Full article

The Chinese tongue sole (Cynoglossus semilaevis) is a marine flatfish of significant economic value, characterized by pronounced female-biased sexual size dimorphism (SSD). Sexual differences of cell number and gene expression within the PIT-1 lineage of the pituitary gland may be crucial for interpreting the female-biased SSD of C. semilaevis. Among hormones secreted by PIT-1 cell lineage, growth hormone (gh), prolactin (prl), prolactin 2 (prl2), and somatolactin (sl) comprise a gene family within the extensive superfamily of class-1 helical cytokines. To better understand the function of the gh/prl/sl in teleost SSD, we firstly identified five genes of the gh/prl/sl family (gh, sl, prl, prl2a, and prl2b) and their receptors (ghra, ghrb, prlra, prlrb, and prlr-like) from C. semilaevis at the genome-wide level. Phylogenetic analyses revealed that the gh/prl/sl family and their receptors were each clustered into five distinct groups. More microsatellites were revealed in the intron 2 of gh gene of female rather than the male and pseudo-male individuals, which is positively correlated with its sexual expression pattern. Interaction network prediction indicated that gh, prl, and sl may collectively contribute to individual growth and development. A FRET experiment showed that ghra can act as a receptor for sl. Additionally, the transcripts of the gh/prl/sl family and their receptors exhibited varying abundances in the pituitary, brain, gonad, and liver of both female and male C. semilaevis, with most ligands showing the highest abundance in the female pituitary. Furthermore, gh and sl were found to be maternally expressed. The knock-down of gh, prl, and sl in the pituitary cells could lead to the expression change of igf1, c-fos, and sos2. This study provided a foundation for further functional characterization of the gh/prl/sl gene family, contributing to a deeper understanding of the growth and reproductive mechanisms in C. semilaevis. Full article

Sex differences in the neurobiology of responses to chronic stress have been widely discussed but remain poorly understood. We found that chronic unpredictable mild stress (CUMS) experienced during adolescence induced different behavioral patterns in adult males and females. Immunohistochemical analysis of the CA1 field of the dorsal and ventral hippocampus revealed no quantitative or morphological changes in astrocytes in the long term after CUMS. Real-time PCR analysis showed no increase in the expression level of SigmaR1 after CUMS relative to individual housekeeping genes. Analysis of mouse cerebral cortex homogenates showed that IL-1β levels only decreased after CUMS in males. However, the SigmaR1 levels were significantly higher in the CUMS groups than in the control groups in both sexes. It can be concluded that biological sex and age influence the response to CUMS, although not in all cases. Further studies are needed to understand the effects of chronic stress on males and females. This is important because men and women have different risks for stress and mental disorders. Full article

The ORA (olfactory receptor class A) gene family in teleosts is related to the V1R (vomeronasal 1 receptors) family in mammals and plays a key role in odor detection. Although ORA genes have been identified in several teleosts, their characteristics in mandarin fish (Siniperca chuatsi) have not been explored. In this study, we conducted a comprehensive genomic analysis of the mandarin fish and discovered a complete ORA gene family consisting of five members located on chromosome 2 (ORA1, ORA2, ORA3, ORA4) and chromosome 16 (ORA6). Phylogenetic, synteny, and gene structure analyses revealed typical exon–intron conservation with strong evidence of purifying selection. Tissue expression analysis showed distinct expression profiles for each ORA gene, with some showing sexual dimorphism in specific tissues. The expression of ORA1 and ORA2 in the olfactory epithelium exhibits sexual dimorphism, while ORA3 shows sexual dimorphism in the brain. In situ hybridization confirmed that ORA1, ORA2, ORA3, and ORA6 are expressed in the microvillar sensory neurons of the olfactory epithelium, while ORA4 is expressed in crypt cells. Additionally, molecular docking simulations indicated that the five ORA proteins have a high binding affinity with seven bile acids (LAC, GLAC, CA, TLCA, 3-KLCA, 7-KLCA, and 12-KLCA), with ORAs showing stronger binding affinity with LCA and CA. This study comprehensively characterizes the ORA gene family in mandarin fish, examining its phylogeny, synteny, gene structure, and selection pressure. Furthermore, we found that each ORA displays a distinct expression pattern across multiple tissues, with notable sexual dimorphism, and shows potential binding interactions with specific bile acids and pheromones. Our findings provide valuable insights that enhance the overall understanding of fish ORAs and their potential functions. Full article

Despite the presentation of similar psychological symptoms, psychological dysfunction secondary to brain injury exhibits markedly lower treatment efficacy compared to injury-independent psychological dysfunction. This gap remains evident, despite extensive research efforts. This review integrates clinical and preclinical evidence to provide a comprehensive overview of the neurobiological mechanisms underlying neuropsychological disorders, focusing on the role of key brain regions in emotional regulation across various forms of brain injuries. It examines therapeutic interventions and mechanistic targets, with the primary goal of identifying pathways for targeted treatments. The review highlights promising therapeutic avenues for addressing injury-associated psychological dysfunction, emphasizing Nrf2, neuropeptides, and nonpharmacological therapies as multi-mechanistic interventions capable of modulating upstream mediators to address the complex interplay of factors underlying psychological dysfunction in brain injury. Additionally, it identifies sexually dimorphic factors as potential areas for further exploration and advocates for detailed investigations into sex-specific patterns to uncover additional contributors to these disorders. Furthermore, it underscores significant gaps, particularly the inadequate consideration of interactions among causal factors, environmental influences, and individual susceptibilities. By addressing these gaps, this review provides new insights and calls for a paradigm shift toward a more context-specific and integrative approach to developing targeted therapies for psychological dysfunction following brain injuries. Full article

Although effects of stress-induced anxiety on the gastrointestinal tract and enteric nervous system (ENS) are well studied, how ENS dysfunction impacts behaviour is not well understood. We investigated whether ENS modulation alters anxiety-related behaviour in rats. We used loperamide, a potent μ-opioid receptor agonist that does not cross the blood–brain barrier, to manipulate ENS function and assess changes in behaviour, gut and brain gene expression, and microbiota profile. Sprague Dawley (male/female) rats were acutely dosed with loperamide (subcutaneous) or control solution, and their behavioural phenotype was examined using open field and elevated plus maze tests. Gene expression in the proximal colon, prefrontal cortex, hippocampus, and amygdala was assessed by RNA-seq and caecal microbiota composition determined by shotgun metagenome sequencing. In female rats, loperamide treatment decreased distance moved and frequency of supported rearing, indicating decreased exploratory behaviour and increased anxiety, which was associated with altered hippocampal gene expression. Loperamide altered proximal colon gene expression and microbiome composition in both male and female rats. Our results demonstrate the importance of the ENS for communication between gut and brain for normo-anxious states in female rats and implicate corticotropin-releasing hormone and gamma-aminobutyric acid gene signalling pathways in the hippocampus. This study also sheds light on sexually dimorphic communication between the gut and the brain. Microbiome and colonic gene expression changes likely reflect localised effects of loperamide related to gut dysmotility. These results suggest possible ENS pharmacological targets to alter gut to brain signalling for modulating mood. Full article

The Chinese soft-shelled turtle (Pelodiscus sinensis) is an economically important species in aquaculture, and its growth pattern is characterized by significant sexual dimorphism. However, the underlying molecular mechanisms of this phenomenon have mostly been investigated in the gonadal tissues of P. sinensis, and there are no articles on sex differentiation from the brain of P. sinensis. Here, we analyzed transcriptomes of the brains of adult male and female P. sinensis using high-throughput Illumina sequencing technology, establishing a set of differential genes and differential transcription factors. The data showed that there were 908 genes with significant differences in expression, of which 357 genes were up-regulated and 551 genes were down-regulated. We annotated using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and screened some genes and pathways related to growth. There were 282 growth-related differential genes and 181 sex-related differential genes. We screened the genes’ growth hormone receptor (GHR) and vascular endothelial growth factor A (VEGFA), which may be related to the growth of P. sinensis. The pathways related to the growth and development of P. sinensis are the growth hormone synthesis, secretion, and action pathway; the MAPK (mitogen-activated protein kinase) pathway; and the calcium signaling pathway. In addition, through gene set enrichment analysis (GSEA), we screened out two genes, LIM homeobox protein 1 (LHX1) and fibroblast growth factor 7 (FGF7), which are related to both growth and sex differentiation, and through protein interaction analysis of these genes, we screened out eight genes, including LHX1, FGF7, GHR, fibroblast growth factor 4 (FGF4), EGFR, BMP3, GLI family zinc finger 2 (GLI2), and neuronal differentiation 1 (NEUROD1), and verified the expression levels of these eight genes in the brain of the P. sinensis by real-time quantitative PCR (qRT-PCR), which supported the reliability and accuracy of our transcriptome analysis. Our study provides a solid foundation for analyzing the mechanisms of sexual-dimorphic growth of P. sinensis and even other turtles. Full article

Background/Objectives: Pregnant women have limited information on the impact of prenatal cannabis exposure (PCE) alone. Our aim was to determine if PCE, without alcohol, tobacco, or illicit drug use, is associated with altered birth outcome measures in obstetrically low-risk women. Methods: In this observational cohort study, pregnant women were recruited between 2019 and 2022 from communities in Washington and Oregon, USA, and enrolled following their first trimester. PCE eligibility required a minimum of three days/week of cannabis use during the first trimester with no required minimum use thereafter. For all participants, illicit drug, nicotine, or alcohol use was exclusionary throughout pregnancy and monitored via urine toxicology at multiple time points. Cannabis use was quantified into delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) mg/day using product weight and potency. Outcome measures included gestational age, weight, length, head circumference, and Apgar scores. Results: Study participants included 37 people in the PCE cohort and 35 controls. Average cannabis use for the PCE cohort was 198.0 mg of THC (SD = 221.2 mg)/day and 3.5 mg of CBD (SD = 4.3)/day. PCE newborns weighed less (38th vs. 52nd percentile, p = 0.04) and were shorter (40th vs. 55th percentile, p = 0.03) for their gestational age than controls. Female PCE newborns had smaller head circumference for gestational age (28th percentile; SD = 23), compared to male PCE newborns (55th percentile; SD = 32; p = 0.02). Conclusions: PCE is associated with reduced birth weight and shorter length for gestational age. The effect of PCE on brain growth may be sexually dimorphic. Future PCE studies should include sex as a biological variable and longitudinally evaluate long-term developmental and physiological outcomes. Full article

Corticotropin-releasing hormone (CRH) neurons within the paraventricular hypothalamic nucleus (PVH) play a crucial role in initiating the neuroendocrine response to stress and are also pivotal in coordination of autonomic, metabolic, and behavioral stress reactions. Although the role of parvocellular CRH^PVH neurons in activation of the hypothalamic–pituitary–adrenal (HPA) axis is well established, the distribution and function of CRH-expressing neurons across the whole central nervous system are less understood. Stress responses activate complex neural networks, which differ depending on the type of stressor and on the sex of the individual. Because of the technical difficulties of localizing CRH neurons throughout the rodent brain, several CRH reporter mouse lines have recently been developed. In this study, we used Crh-IRES-Cre;Ai9 reporter mice to examine whether CRH neurons are recruited in a stressor- or sex-specific manner, both within and outside the hypothalamus. In contrast to the clear sexual dimorphism of CRH-mRNA-expressing neurons, quantification of CRH-reporting, tdTomato-positive neurons in different stress-related brain areas revealed only subtle differences between male and female subjects. These results strongly imply that sex differences in CRH mRNA expression occur later in development under the influence of sex steroids and reflects the limitations of using genetic reporter constructs to reveal the current physiological/transcriptional status of a specific neuron population. Next, we compared the recruitment of stress-related, tdTomato-expressing (putative CRH) neurons in male and female Crh-IRES-Cre;Ai9 reporter mice that had been exposed to predator odor. In male mice, fox odor triggered more c-Fos in the CRH neurons of the paraventricular hypothalamic nucleus, central amygdala, and anterolateral bed nucleus of the stria terminalis compared to females. These results indicate that male mice are more sensitive to predator exposure due to a combination of hormonal, environmental, and behavioral factors. Full article

Background: Helminth infections are associated with cognitive deficits, especially in school-age children. Deworming treatment in heavily infected children improves their short- and long-term memory recall. In mice, intraperitoneal helminth infection with Taenia crassiceps (T. crassiceps) shows sexual dimorphism in terms of the parasite load, immune response, hormone levels, and behavioral changes. We have previously shown poorer short-term memory performance and changes in the concentrations of cytokines and neurotransmitters in the hippocampus, which were replicated in this study. The molecular changes in other brain structures, such as those related to reproduction, are unknown. Methods: Male and female Balb/cAnN mice were chronically infected with T. crassiceps larvae. We determined the peritoneal parasite load and established the presence of cytokines and neurotransmitters in the hippocampus, olfactory bulb, and hypothalamus. Results: The parasite load was higher in female than male infected mice, as expected. In the hippocampus, the neurotransmitters norepinephrine and serotonin increased in males but decreased in females. In contrast, in the olfactory bulb and hypothalamus, the neurotransmitters assessed showed no statistical differences. The cytokine profiles were different in each brain structure. The TNF-α levels in the olfactory bulb and the IL-4 levels in the hippocampus of infected mice were dimorphic; IFN-γ was augmented in both male and female infected animals, although the increase was higher in infected males. Conclusions: The brain responds to peripheral infection with cytokine levels that vary from structure to structure. This could be a partial explanation for the dimorphic behavioral alterations associated with infection, it also demonstrates the synergic interaction between the immune, the endocrine, and the nervous systems. Full article

The endocannabinoid system (ECS) is a lipid signaling system involved in numerous physiological processes, such as endocrine homeostasis, appetite control, energy balance, and metabolism. The ECS comprises endocannabinoids, their cognate receptors, and the enzymatic machinery that tightly regulates their levels within tissues. This system has been identified in various organs, including the brain and liver, in multiple mammalian and non-mammalian species. However, information regarding the sex-specific regulation of the ECS remains limited, even though increasing evidence suggests that interactions between sex steroid hormones and the ECS may ultimately modulate hepatic metabolism and energy homeostasis. Within this framework, we will review the sexual dimorphism of the ECS in various animal models, providing evidence of the crosstalk between endocannabinoids and sex hormones via different metabolic pathways. Additionally, we will underscore the importance of understanding how endocrine-disrupting chemicals and exogenous cannabinoids influence ECS-dependent metabolic pathways in a sex-specific manner. Full article