Neurotoxicity Research最新文献

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social impairments, and repetitive and aggressive behaviors. The pathophysiology of ASD still remains unclear, while the population with ASD is 1/36 in children in the USA in 2024. Evidence suggests a wide range of inconsistent changes in brain-derived neurotrophic factor (BDNF), the most important neurotrophin in the central nervous system, in ASD. The present systematic review investigated studies that examined BDNF levels in three main ASD-like models in rodents [induced by valproic acid (VPA) and propionic acid (PPA), and in the BTBR mouse strain] in accord with PRISMA guidelines and in PubMed database. Forty-two studies were included. Most studies used male rats/mice. The results showed ASD model induced by VPA often leads to decreased BDNF, although unchanged or increased BDNF levels were also reported. ASD model induced by PPA leads to both increased and decreased BDNF. BDNF changes in BTBR mouse strain were also inconsistent. We found that the type of molecular assay appears to be important in evaluating BDNF. Also, few evidence showed a role for postnatal day and sex difference in BDNF changes in ASD-like rodent models. In addition, some studies have shown the potential role of the brain region in BDNF changes in different ASD-like models. In conclusion, it was suggested that inconsistencies in BDNF changes in rodent models of ASD may be related to the type of the molecular assay, the brain region, ASD model, sex, or even the postnatal day. However, evidence is still insufficient.

Arsenic is a prevalent and significant cause of poisoning worldwide, leading to both acute and chronic toxicity. The life-threatening nature of arsenic toxicity is evident in its link to fatal health conditions in different parts and systems of the body. We aimed to conduct a systematic review of the existing literature on long-term health outcomes following arsenic poisoning during infancy. Following the PRISMA 2020 guidelines, we systematically searched the PubMed, Embase, Scopus, Cochrane, and Web of Science databases from their inception up to May 2025. The final selection included seven studies that met the inclusion criteria, with a total of 15,701 participants. A risk assessment of arsenic exposure through powdered milk was done, and a quality assessment was performed. Seven studies were included. Arsenic poisoning due to contaminated milk powder has many effects on multiple organs. This review synthesizes evidence demonstrating that arsenic poisoning during infancy is associated with increased all-cause mortality, primarily attributable to malignancies, neurological disorders, and persistent alterations in somatic development. Exposed individuals exhibited reduced adult height, elevated serum alkaline phosphatase concentrations, and an increased incidence of malignancy. Dental sequelae comprised enamel hypoplasia and gingivitis; dermatological manifestations included persistent punctate hypomelanosis and other cutaneous abnormalities enduring decades. This systematic review delineates the multifaceted long-term health consequences of infantile arsenic poisoning from contaminated milk powder, encompassing malignancies, genitourinary, respiratory, cardiovascular, and neurological diseases. These findings establish arsenic exposure during critical developmental windows as a lifelong health determinant that requires specialized, multidisciplinary medical surveillance protocols. Regulatory standards for arsenic in infant nutrition products need to be reevaluated to prevent similar tragedies from occurring.

Cerebral ischemia-reperfusion (I/R) injury is the main cause of early complications and adverse outcomes after treatment such as myocardial infarction and acute ischemic stroke. In this study, we aimed to explore the functions of insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) and tripartite motif-containing 45 (TRIM45) in neuron injury after cerebral I/R injury. HMC3 cells were exposed to oxygen-glucose deprivation and reoxygenation (OGD/R) to mimic cerebral I/R injury in vitro. Western blot and qRT-PCR were conducted for gene expression. NLR family pyrin domain containing 3 (NLRP3) inflammasome activity was analyzed by western blot. ELISA kits were utilized to determine the concentrations of inflammatory cytokines. Flow cytometry was used to analyze iNOS⁺ cells, CD206⁺ cells and neuron apoptosis. Methylated RNA Immunoprecipitation (meRIP) assay and RIP assay were adopted to analyze the relation between TRIM45 and IGF2BP1. CCK-8 assay and TUNEL assay were adopted for the viability and death of neurons. Mice model of middle cerebral artery occlusion (MCAO) was used to explore the function of IGF2BP2 in cerebral I/R injury. IGF2BP1 level was upregulated in HMC3 cells. IGF2BP1 overexpression promoted NLRP3 inflammasome activation and pro-inflammatory phenotype in OGD/R-stimulated HMC3 cells. Mechanically, IGF2BP1 modulated TRIM45 expression through m6A methylation modification. IGF2BP1 knockdown inhibited NLRP3 inflammasome activation and pro-inflammatory phenotype in OGD/R-stimulated HMC3 cells by m6A methylation modification of TRIM45. Inhibition of IGF2BP1 improved the viability and suppressed the death and apoptosis of neurons in the co-culture system of microglia-like and neurons by regulating TRIM45 expression. Inhibition of IGF2BP1 improved the neurotoxicity of proinflammatory HMC3 cells in co-cultured neurons via reducing the m6A methylation of TRIM45. However, the number of biological replicate samples was relatively small (n = 3) and the results in this study were preliminary study.

Background: Observational studies have shown that exposure to per- and polyfluoroalkyl substances can lead to neurotoxicity. We focus on whether perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) affect brain morphology and the potential molecular mechanisms of toxicity.

Methods: Causal relationship between exposure to both PFOA and PFOS and brain morphology was explored based on Mendelian randomization (MR), and the toxic molecular mechanism was investigated using network toxicology.

Results: MR analysis indicated PFOA exposure reduced brain volume in left parahippocampal (p = 0.018) and right rostral anterior cingulate (p = 0.007), while PFOS exposure decreased volume in left middle temporal (p = 0.036), paracentral (p = 0.022), postcentral (p = 0.014), posterior cingulate (p = 0.002), rostral middle frontal (p = 0.040), superior frontal (p = 0.027), superior parietal (p = 0.033), and in the right hemisphere: inferior parietal (p = 0.017), superior frontal (p = 0.030), superior parietal (p = 0.025), and caudal middle frontal (p = 0.041). GO/KEGG analyses revealed 161 targets linked to the neurotoxicity of PFOA and PFOS, primarily associated with fatty acid metabolism, GABA signaling, neurotransmitter receptor activity, ferroptosis, and PPAR pathways. Molecular docking verified key targets (PPARG, FASN, SCD, CD36, GOT2) underlying the toxicity mechanism.

Conclusions: Exposure to PFOA and PFOS leads to reduced brain volume - neurotoxicity at the macroscopic level. At the molecular level, we identified PPARG, FASN, SCD, CD36, and GOT2 as key targets implicated in the pathology of brain damage induced by PFOA and PFOS.