Offspring behavioral outcomes following maternal allergic asthma in the IL-4-deficient mouse.

Maternal allergic asthma (MAA) during pregnancy has been associated with increased risk of neurodevelopmental disorders in humans, and rodent studies have demonstrated that inducing a T helper-2-mediated allergic response during pregnancy leads to an offspring behavioral phenotype characterized by decreased social interaction and increased stereotypies. The interleukin (IL)-4 cytokine is hypothesized to mediate the neurobehavioral impact of MAA on offspring. Utilizing IL-4 knockout mice, this study assessed whether MAA without IL-4 signaling would still impart behavioral deficits.

Memory deficits and hippocampal cytokine expression in a rat model of ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a complex behavioral disorder characterized by hyperactivity, impulsivity, inattention, and deficits in working memory and time perception. While animal models have advanced our neurobiological understanding of this condition, there are limited and inconsistent data on working and elapsed time memory function. Inflammatory signaling has been identified as a key factor in memory and cognitive impairments, but its role in ADHD remains unclear.

The influence of asthma on neuroinflammation and neurodevelopment: From epidemiology to basic models.

Asthma is a highly heterogeneous inflammatory disease that can have a significant effect on both the respiratory system and central nervous system. Population based studies and animal models have found asthma to be comorbid with a number of neurological conditions, including depression, anxiety, and neurodevelopmental disorders. In addition, maternal asthma during pregnancy has been associated with neurodevelopmental disorders in the offspring, such as autism spectrum disorders and attention deficit hyperactivity disorder.

Characterizing the neuroimmune environment of offspring in a novel model of maternal allergic asthma and particulate matter exposure.

Inflammation during pregnancy is associated with an increased risk for neurodevelopmental disorders (NDD). Increased gestational inflammation can be a result of an immune condition/disease, exposure to infection, and/or environmental factors. Epidemiology studies suggest that cases of NDD are on the rise.

Characterizing the Neuroimmune Environment of Offspring in a Novel Model of Maternal Allergic Asthma and Particulate Matter Exposure.

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by the presence of decreased social interactions and an increase in stereotyped and repetitive behaviors. Epidemiology studies suggest that cases of ASD are on the rise. Similarly, rates of asthma are increasing, and the presence of maternal asthma during pregnancy increases the likelihood of a child being later diagnosed with ASD.

Serum short chain fatty acids mediate hippocampal BDNF and correlate with decreasing neuroinflammation following high pectin fiber diet in mice.

Introduction: Dietary components, such as prebiotic fiber, are known to impact brain chemistry the gut-brain axis. In particular, short chain fatty acids (SCFAs) generated from excessive soluble fiber consumption are thought to impact neuroimmune signaling and brain function through increased production of neurotropic factors. Given reports that high dietary fiber intake is associated with increased mental health and improved quality of life scores, we set out to identify whether changes in SCFA levels as a result of a high soluble fiber diet mediate hippocampal neuroinflammation and brain derived neurotrophic factor (BDNF) in mice.

Maternal Allergic Asthma Induces Prenatal Neuroinflammation.

Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders characterized by impaired social interactions and communication skills and repetitive or stereotyped behaviors. Rates of ASD diagnosis continue to rise, with current estimates at 1 in 44 children in the US (Maenner 2021). Epidemiological studies have suggested a link between maternal allergic asthma and an increased likelihood of having a child diagnosed with ASD.

Allopregnanolone Improves Locomotor Activity and Arousal in the Aged CGG Knock-in Mouse Model of Fragile X-Associated Tremor/Ataxia Syndrome.

Carriers of the fragile X premutation (PM) can develop a variety of early neurological symptoms, including depression, anxiety and cognitive impairment as well as being at risk for developing the late-onset fragile X-associated tremor/ataxia syndrome (FXTAS). The absence of effective treatments for FXTAS underscores the importance of developing efficacious therapies to reduce the neurological symptoms in elderly PM carriers and FXTAS patients. A recent preliminary study reported that weekly infusions of Allopregnanolone (Allop) may improve deficits in executive function, learning and memory in FXTAS patients.

Ten-week high fat and high sugar diets in mice alter gut-brain axis cytokines in a sex-dependent manner.

Diets high in fat and sugar induce inflammation throughout the body, particularly along the gut-brain axis; however, the way these changes in immune signaling mediate one another remains unknown. We investigated cytokine changes in the brain and colon following prolonged high fat or sugar diet in female and male adult C57BL/6 mice. Ten weeks of high fat diet increased levels of TNFα, IL-1β, IL-6, IFNγ, and IL-10 in the female hippocampus and altered cytokines in the frontal cortex of both sexes.

Repeated allergic asthma in early versus late pregnancy differentially impacts offspring brain and behavior development.

Background: Stress during pregnancy and maternal inflammation are two common prenatal factors that impact offspring development. Asthma is the leading chronic condition complicating pregnancy and a common source of prenatal stress and inflammation.

Objective: The goal of this study was to characterize the developmental impact of repeated allergic asthma inflammation during pregnancy on offspring behavioral outcomes and brain inflammation.

Neuroinflammatory and Behavioral Outcomes Measured in Adult Offspring of Mice Exposed Prenatally to E-Cigarette Aerosols.

Background: In an effort to decrease the rates of smoking conventional tobacco cigarettes, electronic cigarettes (e-cigarettes) have been proposed as an effective smoking cessation tool. However, little is known about their toxicological impacts. This is concerning given that e-cigarette use is perceived as less harmful than conventional tobacco cigarettes during pregnancy for both the mother and fetus.

Astroglial-targeted expression of the fragile X CGG repeat premutation in mice yields RAN translation, motor deficits and possible evidence for cell-to-cell propagation of FXTAS pathology.

The fragile X premutation is a CGG trinucleotide repeat expansion between 55 and 200 repeats in the 5'-untranslated region of the fragile X mental retardation 1 (FMR1) gene. Human carriers of the premutation allele are at risk of developing the late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). Characteristic neuropathology associated with FXTAS includes intranuclear inclusions in neurons and astroglia.

Behavioral impact of maternal allergic-asthma in two genetically distinct mouse strains.

Recent population-based studies of expecting mothers identified a unique profile of immune markers that are associated with an increased risk of having a child diagnosed with autism spectrum disorder (ASD). This immune profile, including increased levels of maternal and placental interleukin (IL)-4 and IL-5, is consistent with an immune response found in an allergic-asthma phenotype. Allergies and asthma reflect an imbalance in immune responses including polarization towards T-helper type 2 (T2) responses, with both genetic susceptibility and environmental factors affecting this T-cell polarization.

C57BL/6J bone marrow transplant increases sociability in BTBR T Itpr3/J mice.

Associative studies across a range of neurodevelopmental disorders have revealed a relationship between immune system function and behavioral deficits. These correlations are particularly evident in individuals with autism spectrum disorders (ASD), a developmental disorder characterized by social behavior deficits and noted for its high instances of immune system dysfunction. Mouse models provide a unique opportunity to explore causal links between immune and nervous system function and reveal how changes in these systems alter behavioral profiles.

Maternal immune activation leads to activated inflammatory macrophages in offspring.

Several epidemiological studies have shown an association between infection or inflammation during pregnancy and increased risk of autism in the child. In addition, animal models have illustrated that maternal inflammation during gestation can cause autism-relevant behaviors in the offspring; so called maternal immune activation (MIA) models. More recently, permanent changes in T cell cytokine responses were reported in children with autism and in offspring of MIA mice; however, the cytokine responses of other immune cell populations have not been thoroughly investigated in these MIA models.

Inflammatory macrophage phenotype in BTBR T+tf/J mice.

Although autism is a behaviorally defined disorder, many studies report an association with increased pro-inflammatory cytokine production. Recent characterization of the BTBR T+tf/J (BTBR) inbred mouse strain has revealed several behavioral characteristics including social deficits, repetitive behavior, and atypical vocalizations which may be relevant to autism. We therefore hypothesized that, asocial BTBR mice, which exhibit autism-like behaviors, may have an inflammatory immune profile similar to that observed in children with autism.

Prior fighting experience increases aggression in Syrian hamsters: implications for a role of dopamine in the winner effect.

Winning an aggressive encounter enhances the probability of winning future contests. This phenomenon, known as the winner effect, has been well studied across vertebrate species. While numerous animal models have been developed to study the winner effect in the laboratory setting, large variation in experimental design, choice of species, and housing conditions have resulted in conflicting reports on the behavioral outcomes.

Using mouse models of autism spectrum disorders to study the neurotoxicology of gene-environment interactions.

To better study the role of genetics in autism, mouse models have been developed which mimic the genetics of specific autism spectrum and related disorders. These models have facilitated research on the role genetic susceptibility factors in the pathogenesis of autism in the absence of environmental factors. Inbred mouse strains have been similarly studied to assess the role of environmental agents on neurodevelopment, typically without the complications of genetic heterogeneity of the human population.

Dopamine activity in the lateral anterior hypothalamus modulates AAS-induced aggression through D2 but not D5 receptors.

Treatment with anabolic-androgenic steroids (AAS) throughout adolescence facilitates offensive aggression in Syrian hamsters. In the anterior hypothalamus (AH), the dopaminergic neural system undergoes alterations after repeated exposure to AAS, producing elevated aggression. Previously, systemic administration of selective dopamine receptor antagonists has been shown to reduce aggression in various species and animal models.

Anterior hypothalamic dopamine D2 receptors modulate adolescent anabolic/androgenic steroid-induced offensive aggression in the Syrian hamster.

In the Syrian hamster, treatment with anabolic/androgenic steroids (AAS) throughout adolescence increases dopamine and D2 receptor expression in the anterior hypothalamus (AH), a brain region implicated in the control of aggression. D2 receptor antagonists have reduced aggression in various species and animal models. However, these studies used systemic administration of drugs and reported concomitant changes in mobility.

Immunohistochemical characterization of 5-HT(3A) receptors in the Syrian hamster forebrain.

The Syrian hamster (Mesocricetus auratus) has been extensively used as an animal model to investigate neuronal networks underlying various behaviors where 5-HT(3A) receptors have been found to play a critical role. To date, however, there is no comprehensive description of the distribution of 5-HT(3A) receptors in the Syrian hamster brain. The current study examined the localization of 5-HT(3A) receptors across the neuraxis of the Syrian hamster forebrain using immunohistochemistry.

Interactions between the dopaminergic and GABAergic neural systems in the lateral anterior hypothalamus of aggressive AAS-treated hamsters.

Adolescent exposure to anabolic-androgenic steroids (AAS) produces alterations to various neurochemical systems resulting in an elevated aggressive response. Both the GABAergic and dopaminergic neural systems are implicated in aggression control and are altered in the presence of AAS. The present studies provide a detailed report of the interaction between D2 receptors and GABAergic neurons in the lateral subdivision of the anterior hypothalamus (LAH), a brain region at the center of aggression control.

Adolescent anabolic-androgenic steroid exposure alters lateral anterior hypothalamic serotonin-2A receptors in aggressive male hamsters.

Chronic anabolic-androgenic steroid (AAS) treatment during adolescence facilitates offensive aggression in male Syrian hamsters (Mesocricetus auratus). Serotonin (5-HT) modulates aggressive behavior and has been shown to be altered after chronic treatment with AAS. Furthermore, 5-HT type 2 receptors have been implicated in the control of aggression.

Paliperidone suppresses the development of the aggressive phenotype in a developmentally sensitive animal model of escalated aggression.

Rationale: Atypical antipsychotics are commonly prescribed to clinically referred youngsters for treatment of heightened aggressive behavior associated with various psychiatric disorders. Previously, we demonstrated risperidone's anti-aggressive effects using a well-validated animal model of offensive aggression. Paliperidone, the main active metabolite of risperidone, is a potent serotonin-2A and dopamine-2 receptor antagonist with slightly different pharmacodynamic properties compared to risperidone.