Behavioral effects of toll-like receptor-4 antagonist 'eritoran' in an experimental model of depression: role of prefrontal and hippocampal neurogenesis and γ-aminobutyric acid/glutamate balance.

Depression is the disease of the modern era. The lack of response to the available antidepressants, which were developed on the basis of the monoaminergic deficit hypothesis of depression, has encouraged scientists to think about new mechanisms explaining the pathogenesis of depression. In this context, the inflammatory theory has emerged to clarify many aspects of depression that the previous theories have failed to explain. Toll-like receptor-4 (TLR-4) has a regulatory role in the brain's immune response to stress, and its activation is suggested to play a pivotal role in the pathophysiology of depression. In this study, we tested eritoran (ERI), a TLR-4 receptor-4 antagonist, as a potential antidepressant. We investigated the effect of long-term administration of ERI in three different doses on behavioral changes, hippocampal and prefrontal cortex (PFC) neurogenesis, and γ-aminobutyric acid (GABA)/glutamate balance in male Wistar rats exposed to chronic restraint stress (CRS). Long-term administration of ERI ameliorated CRS-induced depressive-like symptoms and hypothalamic-pituitary-adrenal axis hyperactivity alongside reducing levels of hippocampal and PFC inflammatory cytokines, restoring GABA and glutamate balance, and enhancing PFC and hippocampal neurogenesis, by increasing BDNF gene and protein expression in a dose-dependent manner. The results demonstrate an antidepressant-like activity of ERI in Wistar rats exposed to CRS, which may be largely mediated by its ability to reduce neuroinflammation, increase BDNF, and restore GABA/glutamate balance in prefrontal cortex and hippocampus. Nonetheless, further studies are needed to characterize the mechanism of the antidepressant effect of ERI.

Elucidating the Environmental and Health Risks of Trace Element Pollution in Red Sea Fish from Nuweiba City, Aqaba Gulf, Egypt.

Trace element bioaccumulation in marine organisms is a rising international issue due to possible health concerns for humans. Thirteen trace elements were analyzed in the sediment, water, and muscular tissue of Red Sea fish. Additionally, the average daily intake (EDI), the cancer risk (CR), the hazard index (HI), and the target hazard quotient (THQ) of those elements have been taken into consideration when evaluating any possible health concerns related to their consumption. All species presented quantifiable values in muscle for all the analyzed elements (arsenic (As), lead (Pb), copper (Cu), aluminum (Al), boron (B), iron (Fe), barium (Ba), manganese (Mn), nickel (Ni), cadmium (Cd), chromium (Cr), zinc (Zn), and mercury (Hg), except for Cd and Hg, being Fe and Zn the most accumulated elements in all species. Conversely, in water samples, most elements were undeleted except for aluminum, boron, iron, and zinc. All Red Sea fish, however, had concentrations of Zn, Ni, Fe, Cu, and Mn below the upper limit allowed, although most species had higher levels of As, Cr, and Pb (0.48 ± 0.83-5.10 ± 0.79, 1.97 ± 0.46-5.25 ± 0.67 and 2.12 ± 1.01-6.83 ± 0.93 µg/g, respectively).The studied Red Sea fish showed contamination degrees (CD) of Mn, Cu, Fe, Ni, Zn, and Pb were ≤ 1, indicating minimal contamination, with As and Cr showing higher contamination degrees. However, the pollution index values (MPI-elements) can be represented according to ascending order: Lethrinus ramak < Cephalopholis hemistiktos < Pagellus affinis < Trachurus japonicus < Cheilinus lunulatus < Siganus luridus < Parupeneus forsskali < Caesio suevica. The study found that edible tissues are safe for human consumption, with HI values for children and adults less than ten, indicating negligible non-cancer hazards. However, fish consumption presents health risks due to chromium, lead, and arsenic, with THQ values several times greater than 1, and CR-Ni, CR-Cr, and CR-As values exceeding the acceptable 10-4 value in all studied species. This study provides critical insights into trace element contamination in marine fish species, highlighting the need for ongoing monitoring and proactive measures to ensure safe marine fish consumption in the Aqaba Gulf.

Evaluation of Branched-Chain Amino Acids in Children with Autism Spectrum Disorder and Epilepsy.

Autism spectrum disorder (ASD) and epilepsy run hand-to-hand in their pathophysiology. Epilepsy is not an uncommon finding in patients with ASD. The aim of the present study was to identify the metabolic abnormalities of BCAAs (leucine, isoleucine, and valine) in children with ASD with and without seizures in comparison with neurotypical controls. Also, this study aimed to investigate the presence of epileptiform discharges on electroencephalography (EEG) in ASD patients and to describe the types and frequency of seizures observed. The study included 90 children aged 2-7 years, 30 of whom were diagnosed with both ASD and epilepsy. The other 30 children were diagnosed as ASD without epilepsy, and a comparable 30 normally developed children served as a control group. The groups were matched by age and gender. All patients were referred to the Autism Disorders Clinic for interviews and examinations. The Childhood Autism Rating Scale (CARS) was applied to all study participants to assess the degree of autism. The present study results show that all types of seizures may be identified in ASD children. The median serum levels of BCAAs were lower in ASD children with and without epilepsy than in neurotypical controls. This opens the door for discussion about new etiologies and better categorizations of ASD based on genotype and genetic abnormalities detected. More studies with larger samples are needed to understand ASD better and to more reliable evaluate the association between ASD, EEG changes, seizures, and BCAAs.