The medulla oblongata shows a sex-specific inflammatory response to systemic neonatal lipopolysaccharide.

Early life inflammation has been linked to long-term modulation of behavioural outcomes due to the central nervous system, but it is now becoming apparent it is also linked to dysfunction of visceral physiology. The medulla oblongata contains a number of nuclei critical for homeostasis, therefore we utilised the well-established model of neonatal lipopolysaccharide (LPS) exposure to examine the immediate and long-term impacts of systemic inflammation on the medulla oblongata. Wistar rats were injected with LPS or saline on postnatal days 3 and 5, with tissues collected on postnatal days 7 or 90 in order to assess expression of inflammatory mediators and microglial morphology in autonomic regions of the medulla oblongata. We observed a distinct sex-specific response of all measured inflammatory mediators at both ages, as well as significant neonatal sex differences in inflammatory mediators within saline groups. At both ages, microglial morphology had significant changes in branch length and soma size in a sex-specific manner in response to LPS exposure. This data not only highlights the strong sex-specific response of neonates to LPS administration, but also the significant life-long impact on the medulla oblongata and the potential altered control of visceral organs.

TRAV26-2 T-Cell Receptor Expression Is Associated With Mucosal Lymphocyte Response to Wheat Proteins in Patients With Functional Dyspepsia.

INTRODUCTION: An association between functional dyspepsia (FD) and wheat-containing foods has been reported in observational studies; however, an adaptive response has not been demonstrated. We examined whether antigens present in wheat could provoke a response from FD duodenal lymphocytes. METHODS: Lamina propria mononuclear cells (LPMCs) were isolated from duodenal biopsies from 50 patients with FD and 23 controls. LPMCs were exposed to gluten (0.2 mg/mL) or gliadin (0.2 mg/mL) for 24 hours. Flow cytometry was performed to phenotype lymphocytes. Quantitative PCR was used to measure the expression of gliadin-associated T-cell receptor alpha variant ( TRAV ) 26-2. RESULTS: In response to gliadin (but not gluten) stimulation, the effector Th2-like population was increased in FD LPMCs compared with that in controls and unstimulated FD LPMCs. Duodenal gene expression of TRAV26- 2 was decreased in patients with FD compared with that in controls. We identified a positive association between gene expression of this T-cell receptor variant and LPMC effector Th17-like cell populations in patients with FD, but not controls after exposure to gluten, but not gliadin. DISCUSSION: Our findings suggest that gliadin exposure provokes a duodenal effector Th2-like response in patients with FD, supporting the notion that food antigens drive responses in some patients. Furthermore, these findings suggest that altered lymphocyte responses to wheat proteins play a role in FD pathogenesis.

Maternal probiotic intake attenuates ileal Crh receptor gene expression in maternally separated rat offspring.

Corticotropin-releasing hormone (Crh) and its receptors (Crhr) mediate stress-induced gastrointestinal dysfunctions. Neonatal maternal separation (MS) increased ileal Crhr1 transcript quantities in young rat offspring. Exposure to either MS or adulthood restraint stress increased ileal Crhr1 and Crhr2 transcript quantities only in adult female offspring. Maternal probiotic intervention reversed Crhr overexpression, suggesting a potential early prophylaxis against stress-induced gut dysfunctions.

Investigating the gut-brain axis in a neurodevelopmental rodent model of schizophrenia.

BACKGROUND: Although the aetiology of schizophrenia remains unknown, it has been suggested that it might occur in response to alterations in the gut-brain axis (GBA), the bi-directional communication system between the gut and the brain. The current study aimed to determine whether the "two-hit" animal model of neuropsychopathology (maternal immune activation combined with adolescent cannabinoid exposure), produced abnormalities in the GBA. METHOD: Pregnant Wistar rats were administered the viral mimetic polyI:C on gestational day 19 and offspring were administered the synthetic cannabinoid HU210 from postnatal days 35-48. Evidence of GBA activation was assessed in the hypothalamus, colon and fecal samples from male and female offspring at adolescence and adulthood. RESULTS: Findings were sex-specific with adolescent female offspring exhibiting an increased hypothalamic inflammatory profile, increased hypothalamic CRHR1 mRNA, and decreased fecal expression of Bifidobacterium longum, however, no changes were detected in colonic inflammation or integrity. CONCLUSION: These results indicate that the rat two-hit model, documented to produce behavioural and neuroanatomical abnormalities, also produces hypothalamic and microbiota abnormalities. The results also demonstrate significant sex differences, suggesting that this model may be useful for investigating the role of the GBA in the aetiology of neurodevelopmental disorders such as schizophrenia.