Long-term effects of prophylactic MgSO4 in maternal immune activation rodent model at adolescence and adulthood.

The effects of MgSO4 as an anti-inflammatory agent in pregnant women have been investigated in the last few years. Infections can cause an inflammatory reaction involving the placenta membranes and amniotic cavity. They may have short-term effects on the mother and her fetuses, like preterm birth, cerebral palsy, and developmental delay. Despite the alleged advantages of MgSO4 as a neuroprotective agent in the preterm brain, the long-term molecular and behavioral function of MgSO4 has not been fully elucidated. Here, we investigated the long-term effect of antenatal MgSO4 , during late gestation, on offspring's behavior focusing on cognitive function, motor activity, and social cognition in adolescence and adulthood, and explored its influence on brain gene expression (e.g., ErbB signaling, pro-inflammatory, and dopaminergic markers) in adulthood. A significant abnormal exploratory behavior of offspring of MgSO4 -treated dams was found compared to the control group in both adolescence and adulthood. Furthermore, we found that adult females exposed to MgSO4 under inflammation displayed working and recognition memory impairment. A reduction in IL-6 expression was detected in the prefrontal cortex, and hippocampus specimens derived from LPS-Mg-treated group. In contrast, an imbalanced expression of dopamine 1 and 2 receptors was detected only in prefrontal cortex specimens. Besides, we found that MgSO4 ameliorated the overexpression of the Nrg1 and Erbb4 receptors induced by LPS in the hippocampus. Thus, MgSO4 treatment for preventing brain injuries can adversely affect offspring cognition behavior later in life, depending on the sex and age of the offspring.

Beneficial Effect of Vitamin D on Non-Alcoholic Fatty Liver Disease (NAFLD) Progression in the Zebrafish Model.

A major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma, non-alcoholic fatty liver disease (NAFLD) results from excessive liver fat accumulation. Vitamin D (VitD) plays multiple important roles in diverse physiologic processes. Here, we describe the role of VitD in the complex pathogenesis of NAFLD and explore the possible therapeutic role of VitD supplementation in NAFLD therapy. To compare the effect of VitD to other interventions such as low-calorie diet, we induced NAFLD in young adult zebrafish (Danio rerio, AB strain) and monitored the effects of VitD supplementation on the disease course. The zebrafish administered with high-dose VitD (1.25 µg) had significantly reduced liver fat compared to those that received low-dose VitD (0.049 µg) or caloric restriction. Gene expression analysis revealed that VitD downregulated several pathways that may play a role in NAFLD etiology, which affected fatty acid metabolism, vitamins and their cofactors, ethanol oxidation, and glycolysis. The pathway analysis revealed that the cholesterol biosynthesis pathway and the isoprenoid biosynthetic process pathway were significantly upregulated whereas the small molecule catabolic process pathway significantly downregulated following the exposure of NAFLD zebrafish model to high VitD dose. Therefore, our findings suggest the association of novel biochemical pathways with NAFLD and highlight the potential of VitD supplementation to reverse the severity of NAFLD, especially in younger people.

What we know about the role of corticosteroids in psychiatric disorders; evidence from animal and clinical studies.

Corticosteroids, often known as steroids, are anti-inflammatory medicine prescribed for various conditions. There is accumulating evidence of immune dysregulation in major psychiatric disorders. Significant changes in concentrations of inflammatory biomarkers (i.e., IL-6 and TNF-a) have been previously reported in individuals with schizophrenia, autistic individuals, and depressive patients. Thus, systemic corticosteroids can be used as an adjuvant treatment to reduce inflammation in major psychiatric disorders. However, despite their well-known potent anti-inflammatory and immunosuppressant properties, this treatment is often associated with increased severity of several psychiatric symptoms and relapse. This article reviews the available literature on psychiatric and cognitive changes during corticosteroid therapy. Specifically, we will provide data on the good and the bad of corticosteroid therapy in autism, schizophrenia, mood disorders, and PTSD. This review will summarize the vital role of corticosteroid therapy in social and cognitive behavior.

Short-Term Effect of MgSO4 on the Expression of NRG-ErbB, Dopamine, GABA, and Glutamate Systems in the Fetal Rat Brain.

MgSO4 has been used for the past two decades as neuroprotective treatment in a variety of preterm conditions. Despite the putative advantages of MgSO4 as a neuroprotective agent in the preterm brain, the short- and long-term molecular function of MgSO4 as a neuroprotective agent has not been fully elucidated. Neuregulin (NRG1)-ErbB4 signaling plays a critical role in embryonic brain development, in the biology of dopaminergic, GABAergic, and glutamatergic systems. We hypothesize that this pathway may be associated with the neuroprotective role of MgSO4. The current study aims to investigate the ability of MgSO4 to modulate the normal developing expression pattern of selected genes related to the NRG1-ErbB, dopaminergic, GABAergic, and glutamatergic systems. We demonstrate that overall short-term treatment of dam rats with MgSO4 affects the expression of fetal brain NRG1, NRG3, ErbB4, GAD67, tyrosine hydroxylase (TH), dopamine D2 and D1 receptors, GluN1, and GluN2B. More specifically, the administration of MgSO4 alters the expression of NRG-ErbB, GAD67, TH, and D2R at early gestation day 16 (GD16) regardless of the activation of the maternal immune system by lipopolysaccharide (LPS). Our data suggest that MgSO4 treatment may affect the expression of major neuronal systems and pathways mostly at an early gestation day. These changes might be an initial clue (foundation stone) in the molecular mechanism that underlies the beneficial effect of MgSO4 as a neuroprotective agent for the developmental brain.

Progesterone Attenuates Brain Inflammatory Response and Inflammation-Induced Increase in Immature Myeloid Cells in a Mouse Model.

Progesterone has been shown to regulate immunity during pregnancy, and progesterone administration may reduce inflammation-induced preterm labor. We sought to determine the maternal brain immune response to LPS-induced inflammation in pregnant and non-pregnant mice and whether additional progesterone supplementation attenuates this response. Pregnant (P: n = 9) and non-pregnant mice (NP: n = 9) were randomized to pretreatment with vaginal progesterone/carrier (Replens), daily from days 13 to 16. On days 15 and 16, LPS/saline was administered by intraperitoneal injection (Replens + saline n = 3; Replens + LPS n = 3; progesterone + LPS n = 3). Mice were sacrificed on day 16 and maternal serum analyzed for IL-6 levels and brains analyzed for nNOS, NF-kB, IL-6 protein levels and for immature myeloid cells (IMCs) and microglial activity. LPS significantly increased brain nNOS, NF-kB, and IL-6 in both NP and P mice, with significantly greater responses in P mice. In both NP and P groups, progesterone significantly attenuated LPS-induced increase of nNOS and NF-kB, however with no effect on serum IL-6. In the NP brains, LPS significantly increased IMC population and progesterone reduced the IMC phenotype to levels similar to controls. In P mice, neither LPS nor LPS + progesterone altered the brain IMC population. LPS significantly increased the microglial activity in both NP and P groups, which was attenuated by progesterone. Progesterone attenuates brain inflammatory response to LPS in both NP and P mice although it has no effect on systemic inflammation. In NP mice, progesterone attenuated the increase in brain IMC following LPS administration. Our results suggest that endogenous progesterone during pregnancy may protect the brain from LPS-induced inflammation.