Mouse nerve growth factor suppresses neuronal apoptosis in valproic acid-induced autism spectrum disorder rats by regulating the phosphoinositide-3-kinase/serine/threonine kinase signaling pathway.

BACKGROUND: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by deficits in social communication and restrictive behaviors. Mouse nerve growth factor (mNGF), a neurotrophic factor, is critical for neuronal growth and survival, and the mNGF treatment is considered a promising therapy for neurodegeneration. In light of this, we aimed to evaluate the effect of mNGF on neurological function in ASD. METHODS: An ASD rat model was established by intraperitoneal injection of valproic acid (VPA). Social behavior, learning, and memory of the rats were measured. TdT-mediated dUTP Nick-end labeling and Nissl assays were performed to detect neuronal apoptosis and survival in the hippocampus and prefrontal cortex. Apoptosis-related proteins and oxidative stress markers were detected. RESULTS: mNGF improved locomotor activity, exploratory behavior, social interaction, and spatial learning and memory in VPA-induced ASD rats. In the hippocampus and prefrontal cortex, mNGF suppressed neuronal apoptosis, increased the number of neurons, superoxide dismutase, and glutathione levels, and decreased reactive oxygen species, nitric oxide, TNF-α, and IL-1ß levels compared with the VPA group. In addition, mNGF increased the levels of Bcl-2, p-phosphoinositide-3-kinase (PI3K), and p-serine/threonine kinase (Akt), and decreased the levels of Bax and cleaved caspase-3, while the PI3K inhibitor LY294002 reversed these effects. CONCLUSION: These data suggest that mNGF suppressed neuronal apoptosis and ameliorated the abnormal behaviors in VPA-induced ASD rats, in part, by activating the PI3K/Akt signaling pathway.

A Meta-Analysis on the Impact of Prenatal and Early Childhood Antimicrobial Use on Autism Spectrum Disorders.

OBJECTIVE: To investigate the impact of prenatal and early childhood antimicrobial use on autism spectrum disorders (ASD). DATA SOURCES: We searched PubMed and Embase databases for relevant studies from inception to August 2022. STUDY SELECTION AND DATA EXTRACTION: Peer-reviewed, observational studies were all acceptable. Raw data were extracted into a predefined worksheet and quality analysis was performed using the Newcastle-Ottawa Scale. DATA SYNTHESIS: Nineteen studies were identified in the meta-analysis. Prenatal antimicrobial exposure was not associated with ASD (P = 0.06 > 0.05), whereas early childhood antimicrobial exposure was associated with an increased odds ratio of ASD (OR = 1.17, 95% CI = [1.08-1.27], P value < 0.001). The sibling-matched analysis, with a very limited sample size, suggested that neither prenatal (P = 0.47 > 0.05) nor early childhood (P = 0.13 > 0.05) antimicrobial exposure was associated with ASD. Medical professionals may need to take the possible association into consideration when prescribing an antimicrobial in children. CONCLUSIONS: Early childhood antimicrobial exposure could increase the incidence of ASD. In future studies, it would be necessary to control for confounding factors, such as genetic factors, parenteral age at birth, or low birthweight, to further validate the association.

TCHis mitigate oxidative stress and improve abnormal behavior in a prenatal valproic acid-exposed rat model of autism.

Troxerutin is known for its anti-inflammatory and antioxidative effects in nerve impairment. The purpose of this study is to investigate the effect of troxerutin and cerebroprotein hydrolysate injections (TCHis) on prenatal valproic acid (VPA)-exposed rats. The VPA was administered to pregnant rats on gestational day 12.5 to induce a model of autism. The offspring were given the treatment of TCHis on postnatal day (PND) 21-50. On PND 43-50, the behavioral analysis of offspring was performed after the treatment of TCHis for 1 h. On PND 50, the offspring were harvested and the brains were collected. The hippocampus and prefrontal cortex were isolated for relevant biochemical detections. The administration of TCHis increased pain sensitivity and improved abnormal social behaviors in prenatal VPA-exposed rats. Prenatal exposure of VPA induced neuronal loss and apoptosis, enhanced reactive oxygen species (ROS) production, and promoted oxidative stress in hippocampus and prefrontal cortex, whereas these effects were reversed by the postnatal treatment of TCHis. In addition, postnatal administration of TCHis ameliorated mitochondrial function in hippocampus and prefrontal cortex of prenatal VPA-exposed rats. This study concluded that postnatal treatment of TCHis reduced oxidative stress and ameliorated abnormal behavior in a prenatal VPA-induced rat model of autism.

Electroacupuncture at Zusanli ameliorates the autistic-like behaviors of rats through activating the Nrf2-mediated antioxidant responses.

OBJECTIVE: Emerging evidence suggests that acupuncture plays a neuroprotective role in autism. This study aimed to explore the effect of electroacupuncture at Zusanli (ST36) on autistic-like behaviors and the underlying mechanism. METHOD: Pregnant rats were administered with valproic acid (VPA) on gestational day 12.5 to induce an autism spectrum disorder (ASD) model. The pups were given electroacupuncture at ST36 daily from postnatal day (PND) 28-48. On PND28, the adenoviral vector containing small interfering RNA Nrf2 (Ad-siRNA-Nrf2) was injected into the prefrontal cortex of rats. The behavioral analysis was performed on PND 44-48. On PND48, the animals were euthanized and the brains were collected for further detection. Nissl staining was performed to detect neuronal viability. The biochemical markers of oxidative stress were subsequently measured. RESULT: Electroacupuncture at ST36 ameliorated the locomotor activity, social behavior, spatial learning and memory and repetitive behavior compared with ASD rats. It was notable that the electroacupuncture decreased oxidative stress markers in the tissues of prefrontal cortex, enhanced translocation of nuclear factor erythroid2-related factor2 (Nrf2) from cytoplasm to nucleus, and up-regulated the levels of NADP(H) quinone oxidoreductase (NQO1) and heme oxygenase (HO-1). However, these effects induced by electroacupuncture at ST36 were abolished after injection of Ad-siRNA-Nrf2. CONCLUSION: These data suggested that electroacupuncture at ST36 protected nerve function in ASD rats through Nrf2 activation and the antioxidant response.

Vitamin B1 and B12 mitigates neuron apoptosis in cerebral palsy by augmenting BDNF expression through MALAT1/miR-1 axis.

Through the roles of vitamin B1 and B12 in neuroprotection and in improving cerebral palsy symptoms have been previously noticed, the action mechanism is still unclear. This study aims to investigate the protective effect of vitamin B1 and B12 on neuron injury in cerebral palsy and to clarify the mechanism of vitamin B1 and B12 inhibiting neurons apoptosis, and to focus on the role of lncRNA MALAT1 in this process. In order to investigate the effect of vitamin B1 and B12 on neurons injury in vivo and on neuron apoptosis in vitro, we, respectively, introduced vitamin B1 and B12 into cerebral palsy rat and in apoptosis-induced N2A neurons by Oxygen Glucose Deprivation/reoxygenation (OGD/R). Our results demonstrated that vitamin B1 and B12 treatment improved the motor and memory functions and ameliorated the neurons injury in cerebral palsy rats. OGD/R treatment repressed the expression of MALAT1 and BDNF and the phosphorylation of PI3K and Akt, and enhanced the miR-1 expression, which were all reversed by vitamin B1 and B12 treatment in N2A neurons. Vitamin B1 and B12 inhibited miR-1 expression through MALAT1, promoted BDNF expression and activated PI3K/Akt signaling through the MALAT1/miR-1 axis. Vitamin B1 and B12 suppressed neuron apoptosis by up-regulating BDNF via MALAT1/miR-1 pathway. MALAT1 interference abolished the neuroprotective effect of vitamin B1 and B12 in cerebral palsy rats. Collectively, vitamin B1 and B12 up-regulates BDNF and its downstream PI3K/Akt signaling through MALAT1/miR-1 axis, thus suppressing neuron apoptosis and mitigating nerve injury in cerebral palsy rats.

[Correlation between gut microbiota and behavior symptoms in children with autism spectrum disorder].

OBJECTIVE: To investigate the composition of gut microbiota and its correlation with the severity of behavior symptoms in children with autism spectrum disorder (ASD). METHODS: A total of 30 children with ASD were enrolled as the ASD group, and 20 healthy children matched for age and sex were enrolled as the healthy control group. Related clinical data were analyzed. The V3-V4 hypervariable regions of the bacterial 16S rRNA gene in fecal samples were sequenced. The severity of behavior symptoms in children with ASD was assessed using the autism behavior checklist. The Spearman's correlation analysis was used to investigate the correlation between gut microbiota and the severity of behavior symptoms in children with ASD. RESULTS: There was a significant difference in the composition of gut microbiota between the two groups. Compared with the healthy control group, the ASD group had significant reductions in Shannon index and Shannoneven index (P<0.05), as well as a significant reduction in the percentage of Firmicutes and a significant increase in the percentage of Acidobacteria in feces (P<0.05). In the ASD group, the dominant bacteria were Megamonas, Megasphaera, and Barnesiella, while in the healthy control group, the dominant bacteria were Eubacterium_rectale_group, Ezakiella, and Streptococcus. In the children with ASD, the abundance of Megamonas was positively correlated with the scores of health/physical/behavior and language communication (P<0.05). CONCLUSIONS: The development of ASD and the severity of behavior symptoms are closely associated with the composition of gut microbiota.

LncRNA MIAT overexpression reduced neuron apoptosis in a neonatal rat model of hypoxic-ischemic injury through miR-211/GDNF.

OBJECTIVE: To investigate the underlying mechanism of lncRNA myocardial infarction-associated transcript (MIAT) in hypoxic-ischemic (HI)-induced neonatal cerebral palsy. MATERIALS AND METHODS: Neonatal rat model of HI injury was established to detect the motor function. LncRNA MIAT, miR-211, glial cell line-derived neurotrophic factor (GDNF) and caspase-3 expressions were measured by qRT-PCR or western blot. The apoptosis of Neuro2A cells was detected by flow cytometry. RNA immunoprecipitation (RIP) and RNA pull-down assays were performed to confirm the interaction between MIAT and miR-211. RESULTS: Compared with control group, lncRNA MIAT and GDNF were downregulated in striatal tissues of neonatal rats in HI group and oxygen glucose deprivation (OGD)-induced ischemic injury of Neuro2A cells, whereas miR-211 was up-regulated in striatal tissues of HI group and OGD-induced ischemic injury of Neuro2A cells. LncRNA MIAT interacted with miR-211, and lncRNA MIAT overexpression reduced neuron apoptosis through miR-211. Besides, GDNF expression was positively regulated by lncRNA MIAT and negatively regulated by miR-211 in Neuro2A cells. In vivo experiment proved MIAT promoted motor function and relieved HI injury. CONCLUSION: MIAT overexpression reduced apoptosis of Neuro2A cells through miR-211/GDNF, which relieved HI injury of neonatal rats.