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Olfaction is fundamental in many species of mammals. In rodents, the integrity of this system is required for the expression of parental and sexual behavior, mate recognition, identification of predators, and finding food. Different anatomical and physiological evidence initially indicated the existence of two anatomically distinct chemosensory systems: The main olfactory system (MOS) and the accessory olfactory system (AOS). It was originally conceived that the MOS detected volatile odorants related to food, giving the animal information about the environment. The AOS, on the other hand, detected non-volatile sexually relevant olfactory cues that influence reproductive behaviors and neuroendocrine functions such as intermale aggression, sexual preference, maternal aggression, pregnancy block (Bruce effect), puberty acceleration (Vandenbergh effect), induction of estrous (Whitten effect) and sexual behavior. Over the last decade, several lines of evidence have demonstrated that although these systems could be anatomically separated, there are neuronal areas in which they are interconnected. Moreover, it is now clear that both the MOS and the AOS process both volatile and no-volatile odorants, indicating that they are also functionally interconnected. In the first part of the review, we will describe the behavioral evidence. In the second part, we will summarize data from our laboratory and other research groups demonstrating that sexual behavior in male and female rodents induces the formation of new neurons that reach the main and accessory olfactory bulbs from the subventricular zone. Three factors are essential for the neurons to reach the AOS and the MOS: The stimulation frequency, the stimulus's temporal presentation, and the release of opioids induced by sexual behavior. We propose that the AOS and the MOS are part of a large olfactory system with a high plastic capability, which favors the adaptation of species to different environmental signals. [ABSTRACT FROM AUTHOR]

Maternal care is crucial for the survival and development of offspring. Oxytocin modulates maternal behavior by binding to oxytocin receptors (OXTRs) in various parts of the brain. Previously, we showed that OXTRs are expressed in the anteroventral periventricular nucleus (AVPV) of female, but not male mice. Because the AVPV is involved in the regulation of maternal behavior and oxytocin enhances its induction, this finding leads to the hypothesis that the female specific population of OXTR neurons in the AVPV regulates maternal behavior. To address this hypothesis, OXTR‐Venus reporter mice were used to assess if expression levels of OXTR in the AVPV are changed during the postpartum period. The total number of OXTR‐Venus neurons was significantly greater in postpartum dams compared to virgin females. To assess efferent projections of the AVPV‐OXTR neurons, a Cre‐dependent fluorescent protein (tdTomato) expressing a viral vector was injected into one side of the AVPV of female OXTR‐Cre mice. Fibers expressing tdTomato were found in hypothalamic areas containing oxytocin neurons (the supraoptic and paraventricular nuclei) and the midbrain areas (the ventral tegmental area and periaqueductal gray) that are involved in the regulation of maternal motivation. To assess if activity of the AVPV‐OXTR neurons is involved in the regulation of maternal behaviors, a chemogenetic approach was employed. Specific inhibition of activity of AVPV‐OXTR neurons completely abolished pup retrieval and nest building behaviors. Collectively, these findings demonstrate that AVPV‐OXTR neurons in postpartum female mice constitute an important node in the neural circuitry that regulates maternal behavior. [ABSTRACT FROM AUTHOR]

Sexually dimorphic behaviours, such as parental care, have long been thought to be mainly driven by gonadal hormones. In the past two decades, a few studies have challenged this view, highlighting the direct influence of the sex chromosome complement (XX versus XY or ZZ versus ZW). The African pygmy mouse, Mus minutoides, is a wild mouse species with naturally occurring XY sex reversal induced by a third, feminizing X* chromosome, leading to three female genotypes: XX, XX* and X*Y. Here, we show that sex reversal in X*Y females shapes a divergent maternal care strategy (maternal aggression, pup retrieval and nesting behaviours) from both XX and XX* females. Although neuroanatomical investigations were inconclusive, we show that the dopaminergic system in the anteroventral periventricular nucleus of the hypothalamus is worth investigating further as it may support differences in pup retrieval behaviour between females. Combining behaviours and neurobiology in a rodent subject to natural selection, we evaluate potential candidates for the neural basis of maternal behaviours and strengthen the underestimated role of the sex chromosomes in shaping sex differences in brain and behaviours. All things considered, we further highlight the emergence of a third sexual phenotype, challenging the binary view of phenotypic sexes. [ABSTRACT FROM AUTHOR]

The mammalian preoptic area (POA) has large populations of calbindin (CB), calretinin (CR) and parvalbumin (PV) neurons, but phenotypes of these cells are unknown. Therefore, the question is whether neurons expressing CB, CR, and/or PV are GABAergic or glutamatergic. Double-immunofluorescence staining followed by epifluorescence and confocal microscopy was used to determine the coexpression patterns of CB, CR and PV expressing neurons with vesicular GABA transporters (VGAT) as specific markers of GABAergic neurons and vesicular glutamate transporters (VGLUT 2) as specific markers of glutamatergic neurons. The guinea pig was adopted as, like humans, it has a reproductive cycle with a true luteal phase and a long gestation period. The results demonstrated that in the guinea pig POA of both sexes, ~80% of CB+ and ~90% of CR+ neurons coexpress VGAT; however, one-fifth of CB+ neurons and one-third of CR+ cells coexpress VGLUT. About two-thirds of PV+ neurons express VGAT, and similar proportion of them coexpress VGLUT. Thus, many CB+, CR+ and PV+ neurons may be exclusively GABAergic (VGAT-expressing cells) or glutamatergic (VGLUT-expressing cells); however, at least a small fraction of CR+ cells and at least one-third of PV+ cells are likely neurons with a dual GABA/glutamate phenotype that may coexpress both transporters. [ABSTRACT FROM AUTHOR]

Sex differences in the rates of affective disorders have been recognized for decades. Studies of physiologic sex-related differences in animals and humans, however, have generally yielded little in terms of explaining these differences. Furthermore, the significance of these findings is difficult to interpret given the dynamic, integrative, and highly context-dependent nature of human physiology. In this article, we provide an overview of the current literature on sex differences as they relate to mood disorders, organizing existing findings into five levels at which sex differences conceivably influence physiology relevant to affective states. These levels include the following: brain structure, network connectivity, signal transduction, transcription/translation, and epigenesis. We then evaluate the importance and limitations of this body of work, as well as offer perspectives on the future of research into sex differences. In creating this overview, we attempt to bring perspective to a body of research that is complex, poorly synthesized, and far from complete, as well as provide a theoretical framework for thinking about the role that sex differences ultimately play in affective regulation. Despite the overall gaps regarding both the underlying pathogenesis of affective illness and the role of sex-related factors in the development of affective disorders, it is evident that sex should be considered as an important contributor to alterations in neural function giving rise to susceptibility to and expression of depression. [ABSTRACT FROM AUTHOR]

Background: Hypothalamus is an integral part of the hypothalamo-hypophyseal ovarian axis. It contains several small nuclei that have been implicated in several specialized functions. It is the master endocrine gland because it regulates the activity of the pituitary. The present investigation was planned to elucidate the histomorphological details of different nuclei in the hypothalamus of Indian buffaloes. Methods: The hypothalami of buffaloes (n =52) were collected from local abattoirs and Teaching Veterinary Clinical Complex, GADVASU, Ludhiana. The tissue samples were collected from three levels i.e. the supraoptic, tuberal and the mamillary region of the hypothalamus and processed for paraffin sectioning and the sections were stained with various stains for histomorphological studies. Result: The well-defined cell groups or nuclei were identified both in the coronal and sagittal sections of the hypothalamus in all the reproductive phases. Eight nuclei were distinctly recognized in buffalo hypothalamus at three levels in the coronal sections of the hypothalamus. At the level of optic chiasma, the nuclei were paraventricular nucleus (PVN), supraoptic nucleus (SON) and preopticnucleus (PON); at the tuberal region, there were arcuate nucleus (AN) and ventromedial nucleus (VMN) and at the mammillary region, the lateral mammillary nucleus (LMN), medial mammillary nucleus (MMN) and posterior hypothalamic nucleus (PHN) were identified. Most of the nuclei consisted of a loose or compact heterogeneous collection of neurons. The neurons of the different nuclei were of variable shape. The cytoplasm contained a varied amount of Nissl material. The neurosecretory substance was peripheral in position. Small to large-sized blood vessels were observed in between the neuronal substance. The size of the neurons varied during different stages of reproduction. [ABSTRACT FROM AUTHOR]

Testicular androgens during the perinatal period play an important role in the sexual differentiation of the brain of rodents. Testicular androgens transported into the brain act via androgen receptors or are the substrate of aromatase, which synthesizes neuroestrogens that act via estrogen receptors. The latter that occurs in the perinatal period significantly contributes to the sexual differentiation of the brain. The preoptic area (POA) and the bed nucleus of the stria terminalis (BNST) are sexually dimorphic brain regions that are involved in the regulation of sex-specific social behaviors and the reproductive neuroendocrine system. Here, we discuss how neuroestrogens of testicular origin act in the perinatal period to organize the sexually dimorphic structures of the POA and BNST. Accumulating data from rodent studies suggest that neuroestrogens induce the sex differences in glial and immune cells, which play an important role in the sexually dimorphic formation of the dendritic synapse patterning in the POA, and induce the sex differences in the cell number of specific neuronal cell groups in the POA and BNST, which may be established by controlling the number of cells dying by apoptosis or the phenotypic organization of living cells. Testicular androgens in the peripubertal period also contribute to the sexual differentiation of the POA and BNST, and thus their aromatization to estrogens may be unnecessary. Additionally, we discuss the notion that testicular androgens that do not aromatize to estrogens can also induce significant effects on the sexually dimorphic formation of the POA and BNST. [ABSTRACT FROM AUTHOR]

Ovulation is an essential phenomenon for reproduction in mammalian females along with follicular growth. It is well established that gonadal function is controlled by the neuroendocrine system called the hypothalamus‐pituitary‐gonadal (HPG) axis. Gonadotropin‐releasing hormone (GnRH) neurons, localized in the hypothalamus, had been considered to be the head in governing the HPG axis for a long time until the discovery of kisspeptin. In females, induction of ovulation and folliculogenesis has been linked to a surge mode and pulse mode of GnRH releases, respectively. The mechanisms of how the two modes of GnRH are differently regulated had long remained elusive. The discovery of kisspeptin neurons, distributed in two hypothalamic nuclei, such as the arcuate nucleus in the caudal hypothalamus and preoptic area or the anteroventral periventricular nucleus in the rostral hypothalamic regions, and analyses of the detailed functions of kisspeptin neurons have led marked progress on the understanding of different mechanisms regulating GnRH surges (ovulation) and GnRH pulses (folliculogenesis). The present review will focus on the role of kisspeptin neurons as the GnRH surge generator, including the sexual differentiation of the surge generation system and factors that regulate the surge generator. Comparative aspects between mammalian species are especially focused on. [ABSTRACT FROM AUTHOR]

Prolactin (PRL) is a pleiotropic hormone that was identified in the context of maternal care and its release from the anterior pituitary is primarily controlled by neuroendocrine dopaminergic (NEDA) neurones of the arcuate nucleus of the hypothalamus. The sexually dimorphic nature of PRL physiology and associated behaviours is evident in mammals, even though the number and density of NEDA neurones is reported as not being sexually dimorphic in rats. However, the underlying circuits controlling NEDA neuronal activity and subsequent PRL release are largely uncharacterised. Thus, we mapped whole‐brain monosynaptic NEDA inputs in male and female mice. Accordingly, we employed a rabies virus based monosynaptic tracing system capable of retrogradely mapping inputs into genetically defined neuronal populations. To gain genetic access to NEDA neurones, we used the dopamine transporter promoter. Here, we unravel 59 brain regions that synapse onto NEDA neurones and reveal that male and female mice, despite monomorphic distribution of NEDA neurones in the arcuate nucleus of the hypothalamus, receive sexually dimorphic amount of inputs from the anterior hypothalamic nucleus, anteroventral periventricular nucleus, medial preoptic nucleus, paraventricular hypothalamic nucleus, posterior periventricular nucleus, supraoptic nucleus, suprachiasmatic nucleus, lateral supramammillary nucleus, tuberal nucleus and periaqueductal grey. Beyond highlighting the importance of considering sex as a biological variable when evaluating connectivity in the brain, these results illustrate a case where a neuronal population with similar anatomical distribution has a subjacent sexually dimorphic connectivity pattern, potentially capable of contributing to the sexually dimorphic nature of PRL release and function. [ABSTRACT FROM AUTHOR]

In an effort to systematically describe the neurochemical anatomy of the bovine anterior hypothalamus, we used a series of immunocytochemical markers such as acetylcholine esterase (AChE), arginine–vasopressin (AVP), calbindin (Calb), galanin (Gal), neuropeptide‐Y (NPY), oxytocin (OXT), somatostatin (SST), and vasoactive intestinal peptide (VIP). We also investigated the potential sex difference present in the suprachiasmatic nucleus (SCN) and the vasopressin–oxytocin containing nucleus (VON) of six male and six female Bos taurus. Our study revealed that the cytochemical structure of the cattle anterior hypothalamus follows the blueprint of other mammals. The VON, which was never described before in cattle, showed a sex difference with a 33.7% smaller volume and 23.2% fewer magnocellular neurons (approximately 20–30 μm) in the male. The SCN also did show a sex difference in VIP neurons and volume with a 36.1% larger female nucleus with 28.1% more cells. Additionally, we included five heifers with freemartin syndrome as a new animal model relevant to sexual differentiation in the brain. This is, to the best of our knowledge, the first freemartin study in relation to the brain. Surprisingly, the SCN of freemartin heifers was 32.5% larger than its control male and female counterparts with 29% more VIP cells. Conversely, the freemartin VON had an intermediary size between male and female. To analyze our data, a classical statistical analysis and a novel multivariate and multi‐aspect approach were applied. These findings shed new light on sexual dimorphism in the bovine brain and present this species with freemartins as a valuable animal model in neuroscience. The bovine vasopressin–oxytocin containing nucleus is situated in the hypothalamus between the supraoptic nucleus and the periventricular nucleus. It contains very densely packed magnocellular neurons secreting either vasopressin or oxytocin. We found sex differences between male, female and intersex freemartins not only in the VON but also in the suprachiasmatic nucleus. [ABSTRACT FROM AUTHOR]

HIGD1A (hypoxia-induced gene domain protein-1a), a mitochondrial inner membrane protein present in various cell types, has been mainly associated with anti-apoptotic processes in response to stressors. Our previous findings have shown that Higd1a mRNA is widely expressed across the central nervous system (CNS), exhibiting an increasing expression in the spinal cord from postnatal day 1 (P1) to 15 (P15) and changes in the distribution pattern from P1 to P90. During the first weeks of postnatal life, the great plasticity of the CNS is accompanied by cell death/survival decisions. So we first describe HIGD1A expression throughout the brain during early postnatal life in female and male pups. Secondly, based on the fact that in some areas this process is influenced by the sex of individuals, we explore HIGD1A expression in the sexual dimorphic nucleus (SDN) of the medial preoptic area, a region that is several folds larger in male than in female rats, partly due to sex differences in the process of apoptosis during this period. Immunohistochemical analysis revealed that HIGD1A is widely but unevenly expressed throughout the brain. Quantitative Western blot analysis of the parietal cortex, diencephalon, and spinal cord from both sexes at P1, P5, P8, and P15 showed that the expression of this protein is predominantly high and changes with age but not sex. Similarly, in the sexual dimorphic nucleus, the expression of HIGD1A varied according to age, but we were not able to detect significant differences in its expression according to sex. Altogether, these results suggest that HIGD1A protein is expressed in several areas of the central nervous system following a pattern that quantitatively changes with age but does not seem to change according to sex. [ABSTRACT FROM AUTHOR]

Sex steroids play a major role in sexually dimorphic brain development during not only the perinatal period but also the pubertal period. We previously showed that, in male mice, the estrogen receptor-α (Esr1) and aromatase (Cyp19a1) genes are essential to the sexually dimorphic formation of the anteroventral periventricular nucleus (AVPV) and the principal nucleus of the bed nucleus of the stria terminalis (BNSTp), but the estrogen receptor-β (Esr2) gene is not necessary. We also showed that the androgen receptor (Ar) gene is essential to the sexually dimorphic formation of the BNSTp. These genes are expressed in the AVPV and BNSTp of perinatal mice. However, it remains unknown whether these genes are expressed in the AVPV and BNSTp during puberty, and whether the expression, if any, differs by sex, age, and brain region. Here, we dissected the AVPV and BNSTp from Nissl-stained brain sections of male and female mice on postnatal day (PD) 20 (prepuberty), PD30 (puberty onset in females), PD40 (puberty onset in males), and PD60 (young adult) using a laser microdissection system. We then examined the mRNA levels of Esr1, Esr2, Cyp19a1, and Ar in these brain regions. In the AVPV, Esr1 mRNA levels were greater in females than males during PD20-60. Esr2 and Ar mRNA expressions did not differ between sexes. Ar mRNA levels were higher at PD30 than PD20. Cyp19a1 mRNA was not detected in the AVPV at PD20-60. In the BNSTp, Esr1 and Esr2 mRNA levels were higher in females than in males during PD20-60, although the mRNA levels of Cyp19a1 and Ar did not differ between sexes. Additionally, we revealed that orchiectomy at PD20 induced a failure of normal formation of the male BNSTp and testosterone replacement in the prepubertal period rescued the effect of orchiectomy at PD20. Taken together, it is suggested that pubertal testosterone transported to the AVPV is not converted to estradiol there and does not act via ESR1 and ESR2. By contrast, the formation of the male BNSTp may be affected by testicular testosterone during puberty via AR and/or via ESR1 after conversion to estradiol by CYP19A1. [ABSTRACT FROM AUTHOR]

The overall bauplan of the tetrapod brain is highly conserved, yet significant variations exist among species in terms of brain size, structural composition and cellular diversity. Understanding processes underlying neural and behavioral development in a wide range of species is important both from an evolutionary developmental perspective as well as for the identification of cell sources with postdevelopmental neurogenic potential. Here, we characterize germinal processes in the brain of Notophthalmus viridescens and Pleurodeles waltl during both development and adulthood. Using a combination of cell tracking tools, including clonal analyses in new transgenic salamander lines, we examine the origin of neural stem and progenitor cells found in the adult brain, determine regional variability in cell cycle length of progenitor cells, and show spatiotemporally orchestrated neurogenesis. We analyze how maturation of different brain regions and neuronal subpopulations are linked to the acquisition of complex behaviors, and how these behaviors are altered upon chemical ablation of dopamine neurons. Our data analyzed from an evolutionary perspective reveal both common and species-specific processes in tetrapod brain formation and function. [ABSTRACT FROM AUTHOR]

In mammals, biological rhythms are driven by a master circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Recently, we have demonstrated that in the camel, the daily cycle of environmental temperature is able to entrain the master clock. This raises several questions about the structure and function of the SCN in this species. The current work is the first neuroanatomical investigation of the camel SCN. We carried out a cartography and cytoarchitectural study of the nucleus and then studied its cell types and chemical neuroanatomy. Relevant neuropeptides involved in the circadian system were investigated, including arginine-vasopressin (AVP), vasoactive intestinal polypeptide (VIP), met-enkephalin (Met-Enk), neuropeptide Y (NPY), as well as oxytocin (OT). The neurotransmitter serotonin (5-HT) and the enzymes tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) were also studied. The camel SCN is a large and elongated nucleus, extending rostrocaudally for 9.55 ± 0.10 mm. Based on histological and immunofluorescence findings, we subdivided the camel SCN into rostral/preoptic (rSCN), middle/main body (mSCN) and caudal/retrochiasmatic (cSCN) divisions. Among mammals, the rSCN is unusual and appears as an assembly of neurons that protrudes from the main mass of the hypothalamus. The mSCN exhibits the triangular shape described in rodents, while the cSCN is located in the retrochiasmatic area. As expected, VIP-immunoreactive (ir) neurons were observed in the ventral part of mSCN. AVP-ir neurons were located in the rSCN and mSCN. Results also showed the presence of OT-ir and TH-ir neurons which seem to be a peculiarity of the camel SCN. OT-ir neurons were either scattered or gathered in one isolated cluster, while TH-ir neurons constituted two defined populations, dorsal parvicellular and ventral magnocellular neurons, respectively. TH colocalized with VIP in some rSCN neurons. Moreover, a high density of Met-Enk-ir, 5-HT-ir and NPY-ir fibers were observed within the SCN. Both the cytoarchitecture and the distribution of neuropeptides are unusual in the camel SCN as compared to other mammals. The presence of OT and TH in the camel SCN suggests their role in the modulation of circadian rhythms and the adaptation to photic and non-photic cues under desert conditions. [ABSTRACT FROM AUTHOR]

Parental care is found in species across the animal kingdom, from small insects to large mammals, with a conserved purpose of increasing offspring survival. Yet enormous variability exists between different species and between the sexes in the pattern and level of parental investment. Here, we review the literature on the neurobiological mechanisms underlying maternal and paternal care, especially in rodents, and discuss the relationship between sex differences in behavior and sexual dimorphism in the brain. We argue that although several brain regions and circuits regulating parental care are shared by both sexes, some of the fundamental components comprising the maternal brain are innate and sex specific. Moreover, we suggest that a more comprehensive understanding of the underlying mechanisms can be achieved by expanding the methodological toolbox, applying ethologically relevant approaches such as nontraditional wild-derived animal models and complex seminatural experimental set-ups. [ABSTRACT FROM AUTHOR]

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Sex differences are widespread across vertebrate nervous systems. Such differences are sometimes reflected in the neural substrate via neuroanatomical differences in brain region volume. One brain region that displays sex differences in its associated functions and pathologies is the striatum, including the caudate-putamen (dorsal striatum), nucleus accumbens core and shell (ventral striatum). The extent to which these differences can be attributed to alterations in volume is unclear. We thus tested whether the volumes of the caudate-putamen, nucleus accumbens core, and nucleus accumbens shell differed by region, sex, and hemisphere in adult Sprague-Dawley rats. As a positive control for detecting sex differences in brain region volume, we measured the sexually dimorphic nucleus of the medial preoptic area (SDN-POA). As expected, SDN-POA volume was larger in males than in females. No sex differences were detected in the volumes of the caudate-putamen, nucleus accumbens core or shell. Nucleus accumbens core volume was larger in the right than left hemisphere across males and females. These findings complement previous reports of lateralized nucleus accumbens volume in humans, and suggest that this may possibly be driven via hemispheric differences in nucleus accumbens core volume. In contrast, striatal sex differences seem to be mediated by factors other than striatal region volume. This conclusion is presented within the context of a detailed review of studies addressing sex differences and similarities in striatal neuroanatomy. [ABSTRACT FROM AUTHOR]

Although considerable progress has been made in our understanding of brain function, many questions remain unanswered. The ultimate goal of studying the brain is to understand the connection between brain structure and function and behavioural outcomes. Since sex differences in brain morphology were first observed, subsequent studies suggest different functional organization of the male and female brains in humans. Sex and gender have been identified as being a significant factor in understanding human physiology, health and disease, and the biological differences between the sexes is not limited to the gonads and secondary sexual characteristics, but also affects the structure and, more crucially, the function of the brain and other organs. Significant variability in brain structures between individuals, in addition to between the sexes, is factor that complicates the study of sex differences in the brain. In this review, we explore the current understanding of sex differences in the brain, mostly focusing on preclinical animal studies. [ABSTRACT FROM AUTHOR]

Steroid hormones intervene in the structural and functional regulation of neuronal processes during development and thus determine brain differentiation. The effects of estrogens are mediated by two transcription factors, namely estrogen receptor α (ER-α) and estrogen receptor β (ER-β), that regulate the expression of target genes through their binding to specific DNA target sequences. We describe the mRNA expression of ER-α and ER-β in the hypothalamus of developing male and female bovines as revealed by quantitative real-time polymerase chain reaction, and the distribution of the two ERs in hypothalamic sections of all fetal stages as shown by immunohistochemistry. The expression profiles of the mRNAs of both ERs are mutually correlated throughout the gestation period, and their levels increase significantly in the last stages of gestation. No sexual differences in the mRNA expression of either ER-α or ER-β have been found in our fetal specimens. The use of specific antisera against ER-α and ER-β has allowed us to characterize and confirm the distribution of these receptors in the hypothalami of all fetal stages considered. Our results offer detailed information concerning the distribution of ER-α and ER-β in the developing bovine hypothalamus and provide additional insights into the processes involved in the hypothalamic development of a mammal with a long gestation and a highly gyrencephalic brain. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is one of the most serious threats in modern medicine which requires the constant monitoring of emerging trends amongst clinical isolates. However, very limited surveillance data is available in the Latvian context. In the present study, we conducted a retrospective analysis of microbiological data from one of the largest public multispecialty hospitals in Latvia from 2017 to 2020. AMR trends for 19 gram-negative bacterial (GNB) genera were investigated. During the study period, 11,437 isolates were analyzed with Escherichia spp. (34.71%), Klebsiella spp. (19.22%) and Acinetobacter spp. (10.05%) being the most isolated. Carbapenems like Meropenem and Ertapenem were the most effective against GNBs (3% and 5.4% resistance rates, respectively) while high resistance rates (>50%) were noted against both Ampicillin and Amoxicillin/Clavulanic acid. Enterobacter spp. and Klebsiella spp. showed a significant increase in resistance rate against Ertapenem (p = 0.000) and Trimethoprim-Sulfamethoxazole (p = 0.000), respectively. A decrease in the prevalence of Extended-Spectrum Beta-Lactamase positive (ESBL+) Enterobacterales was noted. Despite the lower prescription levels of the penicillin group antimicrobials than the European average (as reported in ESAC-Net Surveillance reports), GNBs showed high average resistant rates, indicating the role of ESBL+ isolates in driving the resistance rates. Constant and careful vigilance along with proper infection control measures are required to track the emerging trends in AMR in GNBs. [ABSTRACT FROM AUTHOR]

Prenatal exposure to bisphenol A (BPA) influences the development of sex differences neurologically and behaviorally across many species of vertebrates. These effects are a consequence of BPA's estrogenic activity and its ability to act as an endocrine disrupter even, at very low doses. When exposure to BPA occurs during critical periods of development, it can interfere with the normal activity of sex steroids, impacting the fate of neurons, neural connectivity and the development of brain regions sensitive to steroid activity. Among the most sensitive behavioral targets of BPA action are behaviors that are characterized by a sexual dimorphism, especially emotion and anxiety related behaviors, such as the amount of time spent investigating a novel environment, locomotive activity and arousal. Moreover, in some species of rodents, BPA exposure affected males' sexual behaviors. Interestingly, these behaviors are at least in part modulated by the catecholaminergic system, which has been reported to be a target of BPA action. In the present study we investigated the influence of prenatal exposure of mice to a very low single dose of BPA on emotional and sexual behaviors and on the density and binding characteristics of alpha2 adrenergic receptors. Alpha2 adrenergic receptors are widespread in the central nervous system and they can act as autoreceptors, inhibiting the release of noradrenaline and other neurotransmitters from presynaptic terminals. BPA exposure disrupted sex differences in behavioral responses to a novel environment, but did not affect male mice sexual behavior. Importantly, BPA exposure caused a change in the binding affinity of alpha2 adrenergic receptors in the locus coeruleus and medial preoptic area (mPOA) and it eliminated the sexual dimorphism in the density of the receptors in the mPOA. [ABSTRACT FROM AUTHOR]