Maternal immune activation by toll-like receptor 7 agonist during mid-gestation increases susceptibility to blood-brain barrier leakage after puberty.

Maternal immune activation (MIA), a maternal stressor, increases risk for neuropsychiatric diseases, such as Major Depressive Disorder in offspring. MIA of toll-like receptor 7 (TLR7) initiates an immune response in mother and fetuses in a sex-selective manner. The paraventricular nucleus of the hypothalamus (PVN), a brain region that is sexually dimorphic and regulates hypothalamic-pituitary-adrenal (HPA) stress responses, have been tied to stress-related behaviors (i.

Prenatal Dexamethasone Programs Autonomic Dysregulation in Female Rats.

Autonomic dysfunction is associated with cardiovascular and neurological disease, including hypertension, heart failure, anxiety, and stress-related disorders. Prior studies demonstrated that late gestation exposure to dexamethasone (DEX) resulted in female-biased increases in stress-responsive mean arterial pressure (MAP) and heart rate (HR), suggesting a role for glucocorticoid-mediated programming of autonomic dysfunction. The present study investigated the influence of sympathetic (SYM) or parasympathetic (PS) blockade on cardiovascular function in male and female rat offspring of mothers injected with DEX (gestation days [GD]18-21).

Sex specific effects of environmental toxin-derived alpha synuclein on enteric neuronal-epithelial interactions.

Background: Parkinson's Disease (PD) is a neurodegenerative disorder with prodromal gastrointestinal (GI) issues often emerging decades before motor symptoms. Pathologically, PD can be driven by accumulation of misfolded alpha synuclein (aSyn) protein in the brain and periphery, including the GI tract. Disease epidemiology differs by sex, with men twice as likely to develop PD.

Maternal immune activation with toll-like receptor 7 agonist during mid-gestation alters juvenile and adult developmental milestones and behavior.

Infections during pregnancy are associated with increased risk for adult neuropsychiatric disease, such as major depressive disorder, schizophrenia, and autism spectrum disorder. In mouse models of maternal immune activation (MIA), different toll-like receptors (TLRs) are stimulated to initiate inflammatory responses in mother and fetus. The goal of this study was to determine sex-dependent aspects of MIA using a TLR7/8 agonist, Resiquimod (RQ), on neurodevelopment.

A Microphysiological System for Studying Barrier Health of Live Tissues in Real Time.

Epithelial cells create barriers that protect many different components in the body from their external environment. The gut in particular carries bacteria and other infectious agents. A healthy gut epithelial barrier prevents unwanted substances from accessing the underlying lamina propria while maintaining the ability to digest and absorb nutrients.

Evaluating different models of maternal stress on stress-responsive systems in prepubertal mice.

Introduction: Maternal adversity during pregnancy influences neurodevelopment in human and model animal offspring. Adversity can result from stressors coming from many different directions ranging from environmental to nutritional and physiological to immune (e.g.

Microfluidic organotypic device to test intestinal mucosal barrier permeability .

To protect the body from external pathogens, the intestines have sophisticated epithelial and mucosal barriers. Disruptions to barrier integrity are associated with a variety of disorders such as irritable bowel disease, Crohn's disease, and celiac disease. One critical component of all barriers are collagens in the extracellular matrix.

H-NMR Profiling of Short-Chain Fatty Acid Content from a Physiologically Accurate Gut-on-a-Chip Device.

It has been shown that short-chain fatty acids (SCFAs) produced by the gut microbiome are of importance to host tissue health; however, measuring such compounds in biological samples is often limited to using hours to days old fecal and blood plasma samples. Organ-on-a-chip models have been created to simplify the complexity but struggle to reproduce the full biology of the gut specifically. We recently reported a tissue-in-a-chip gut model that incorporates gut explanted tissue into a microfluidic device.

Sex differences in anatomic plasticity of gut neuronal-mast cell interactions.

The gut wall houses mast cells that are anatomically situated near enteric neuronal fibers. Roles of specific neuropeptides in modulating function of immune components like mast cells in response to challenge with bacterial components are relatively unknown. Investigating such interactions requires models that include diverse cellular elements in native anatomic arrangements.

Vasoactive intestinal peptide regulates ileal goblet cell production in mice.

Innervation of the intestinal mucosa has gained more attention with demonstrations of tuft and enteroendocrine cell innervation. However, the role(s) these fibers play in maintaining the epithelial and mucus barriers are still poorly understood. This study therefore examines the proximity of mouse ileal goblet cells to neuronal fibers, and the regulation of goblet cell production by vasoactive intestinal peptide (VIP).

Human colon function ex vivo: Dependence on oxygen and sensitivity to antibiotic.

Background: Human intestines contain a heterogeneous collection of cells that include immune, neural and epithelial elements interacting in a highly complex physiology that is challenging to maintain ex vivo. There is an extreme oxygen gradient across the intestinal wall due in part to microbiota in the lumen and close to the gut wall, which complicates the design of tissue culture systems. The current study established the use of an organotypic slice model of human intestinal tissue derived from colonoscopy biopsies to study host-microbial interactions after antibiotic treatment, and the influence of oxygen concentration on gut wall function.

From organotypic culture to body-on-a-chip: A neuroendocrine perspective.

The methods used to study neuroendocrinology have been as diverse as the discoveries to come out of the field. Maintaining live neurones outside of a body in vitro was important from the beginning, building on methods that dated back to at least the first decade of the 20th Century. Neurosecretion defines an essential foundation of neuroendocrinology based on work that began in the 1920s and 1930s.

Sex differences in major depression and comorbidity of cardiometabolic disorders: impact of prenatal stress and immune exposures.

Major depressive disorder topped ischemic heart disease as the number one cause of disability worldwide in 2012, and women have twice the risk of men. Further, the comorbidity of depression and cardiometabolic disorders will be one of the primary causes of disability worldwide by 2020, with women at twice the risk. Thus, understanding the sex-dependent comorbidities has public health consequences worldwide.

Powering ex vivo tissue models in microfluidic systems.

This Frontiers review analyzes the rapidly growing microfluidic strategies that have been employed in attempts to create physio relevant 'organ-on-chip' models using primary tissue removed from a body (human or animal). Tissue harvested immediately from an organism, and cultured under artificial conditions is referred to as ex vivo tissue. The use of primary (organotypic) tissue offers unique benefits over traditional cell culture experiments, and microfluidic technology can be used to further exploit these advantages.

Embryonic Exposure to Dexamethasone Affects Nonneuronal Cells in the Adult Paraventricular Nucleus of the Hypothalamus.

Neurons in the paraventricular nucleus of the hypothalamus (PVN) integrate peripheral signals and coordinate responses that maintain numerous homeostatic functions. An excess of glucocorticoids during fetal development results in long-lasting consequences tied to disrupted PVN development. The PVN contains a distinct neuronal population and a threefold greater vascular density than the surrounding brain regions that prepubertally is reduced in offspring exposed to excess glucocorticoids .

An organotypic slice model for ex vivo study of neural, immune, and microbial interactions of mouse intestine.

Organotypic tissue slices provide seminatural, three-dimensional microenvironments for use in ex vivo study of specific organs and have advanced investigative capabilities compared with isolated cell cultures. Several characteristics of the gastrointestinal tract have made in vitro models for studying the intestine challenging, such as maintaining the intricate structure of microvilli, the intrinsic enteric nervous system, Peyer's patches, the microbiome, and the active contraction of gut muscles. In the present study, an organotypic intestinal slice model was developed that allows for functional investigation across regions of the intestine.

GnRH Neuron-Specific Ablation of Gαq/11 Results in Only Partial Inactivation of the Neuroendocrine-Reproductive Axis in Both Male and Female Mice: In Vivo Evidence for Kiss1r-Coupled Gαq/11-Independent GnRH Secretion.

Unlabelled: The gonadotropin-releasing hormone (GnRH) is the master regulator of fertility and kisspeptin (KP) is a potent trigger of GnRH secretion from GnRH neurons. KP signals via KISS1R, a Gαq/11-coupled receptor, and mice bearing a global deletion of Kiss1r (Kiss1r(-/-)) or a GnRH neuron-specific deletion of Kiss1r (Kiss1r(d/d)) display hypogonadotropic hypogonadism and infertility. KISS1R also signals via β-arrestin, and in mice lacking β-arrestin-1 or -2, KP-triggered GnRH secretion is significantly diminished.

The Influence of Gonadal Steroid Hormones on Immunoreactive Kisspeptin in the Preoptic Area and Arcuate Nucleus of Developing Agonadal Mice with a Genetic Disruption of Steroidogenic Factor 1.

Kisspeptin, a regulator of reproductive function and puberty in mammals, is expressed in the rostral (anteroventral) periventricular nucleus (AVPV) and arcuate nucleus (Arc), and its expression is at least partially regulated by estradiol in rodents. The aim of the present study was to determine contributions of genetic factors and gonadal steroid hormones to the sexual differentiation of kisspeptin-immunoreactive (kisspeptin-ir) cell populations in the AVPV and Arc during postnatal development using agonadal steroidogenic factor 1 (SF-1) knockout (KO) mice. To examine the effects of gonadal hormones on pubertal development of kisspeptin neurons, SF-1 KO mice were treated with estradiol benzoate (EB) from postnatal day (P)25 to P36, and their brains were examined at P36.

Social isolation during puberty affects female sexual behavior in mice.

Exposure to stress during puberty can lead to long-term behavioral alterations in adult rodents coincident with sex steroid hormone-dependent brain remodeling and reorganization. Social isolation is a stress for social animals like mice, but little is known about the effects of such stress during adolescence on later reproductive behaviors. The present study examined sexual behavior of ovariectomized, estradiol and progesterone primed female mice that were individually housed from 25 days of age until testing at approximately 95 days, or individually housed from day 25 until day 60 (during puberty), followed by housing in social groups.

Gonadectomy prior to puberty decreases normal parental behavior in adult mice.

Sex steroid hormones secreted by gonads influence development and expression of many behaviors including parental behaviors. The capacity to display many behaviors develops under the influence of sex steroid hormones; it begins with gonadal differentiation and lasts through puberty. The timing of gonadectomy may have important and long lasting effects on the organization and activation of neural circuits regulating the expression of different behaviors.

Embryonic GABA(B) receptor blockade alters cell migration, adult hypothalamic structure, and anxiety- and depression-like behaviors sex specifically in mice.

Neurons of the paraventricular nucleus of the hypothalamus (PVN) regulate the hypothalamic- pituitary-adrenal (HPA) axis and the autonomic nervous system. Females lacking functional GABA(B) receptors because of a genetic disruption of the R1 subunit have altered cellular characteristics in and around the PVN at birth. The genetic disruption precluded appropriate assessments of physiology or behavior in adulthood.

KISS1R signals independently of Gαq/11 and triggers LH secretion via the β-arrestin pathway in the male mouse.

Hypothalamic GnRH is the master regulator of the neuroendocrine reproductive axis, and its secretion is regulated by many factors. Among these is kisspeptin (Kp), a potent trigger of GnRH secretion. Kp signals via the Kp receptor (KISS1R), a Gαq/11-coupled 7-transmembrane-spanning receptor.