Introduction: This study aimed to explore the impact and mechanism of Scutellariae radix (SR), dried root of Scutellaria baicalensis Georgi of Labiatae, on prenatal stress (PS)-induced anxiety-like and depression-like behavior in the offspring in a mouse prenatal stress model.
Methods: The open field test (OFT), tail suspension test (TST), and forced swimming test (FST) were utilized to assess the behavior of the offspring. Histological changes were evaluated using HE staining and Nissl staining. ELISA was employed to detect the levels of related factors in the serum and fetal brains of offspring mice. Immunohistochemistry was used to determine the expressions of doublecortin and neurotrophic factors in the hippocampus, and RT-PCR reflected the expression of factors in the hippocampus and placenta of offspring mice. These various techniques collectively provided insight into the neurodevelopmental status by detecting indicators related to neurodevelopmental status. LC-MS/MS and molecular docking were used to clarify the chemical constituents and the pharmacodynamic components in S. radix.
Results: S. radix ameliorated prenatal stress-induced anxiety-like and depression-like behavior in the offspring. It also alleviated hippocampal neurogenesis impairment caused by prenatal stress and restored abnormal expression of hippocampal glutamate (Glu) and brain-derived neurotrophic factor in the offspring. Additionally, S. radix maintained normal 11β-HSD1 expression in the placenta of prenatal stress mice, ensuring a normal level of glucocorticoids (GCs) and glucocorticoid receptors (GRs) in the fetus. Furthermore, S. radix increased the mRNA expression of GR and 11β-HSD2 while decreasing the mRNA expression of 11β-HSD1, thereby normalizing levels of serum CRH, ACTH, and GC in the offspring. Finally, docking results indicated that baicalein, wogonin, wogonoside, and baicalin exhibited stronger binding ability with the target.
Conclusion: The results of our study indicate that S. radix may have the potential to alleviate prenatal stress-induced anxiety-like and depression-like behaviors in offspring, at least partially through protecting placental barrier function, reversing HPA axis hyperfunction, and ameliorating neurodevelopmental dysfunction.
Introduction: Acute onset of severe psychiatric symptoms or regression may occur in children with premorbid neurodevelopmental disorders, although typically developing children can also be affected. Infections or other stressors are likely triggers. The underlying causes are unclear, but a current hypothesis suggests the convergence of genes that influence neuronal and immunological function. We previously identified 11 genes in pediatric acute-onset neuropsychiatric syndrome (PANS), in which two classes of genes related to either synaptic function or the immune system were found. Among the latter, three affect the DNA damage response (DDR): PPM1D, CHK2, and RAG1. We now report an additional 17 cases with mutations in PPM1D and other DDR genes in patients with acute onset of psychiatric symptoms and/or regression that their clinicians classified as PANS or another inflammatory brain condition.
Methods: We analyzed genetic findings obtained from parents and carried out whole-exome sequencing on a total of 17 cases, which included 3 sibling pairs and a family with 4 affected children.
Results: The DDR genes include clusters affecting p53 DNA repair (PPM1D, ATM, ATR, 53BP1, and RMRP), and the Fanconi Anemia Complex (FANCE, SLX4/FANCP, FANCA, FANCI, and FANCC). We hypothesize that defects in DNA repair genes, in the context of infection or other stressors, could contribute to decompensated states through an increase in genomic instability with a concomitant accumulation of cytosolic DNA in immune cells triggering DNA sensors, such as cGAS-STING and AIM2 inflammasomes, as well as central deficits on neuroplasticity. In addition, increased senescence and defective apoptosis affecting immunological responses could be playing a role.
Conclusion: These compelling preliminary findings motivate further genetic and functional characterization as the downstream impact of DDR deficits may point to novel treatment strategies.
.Introduction: Birth asphyxia-induced encephalopathy is a major cause of long-term neurological morbidity, including cognitive and motor deficits. A proposed treatment is maternal creatine supplementation for prophylactic neuroprotection. This study examined how maternal creatine supplementation with or without birth asphyxia affected the behaviour of spiny mice offspring.
Methods: On day 20 of gestation (mid-gestation; term = 39 days), dams were randomly allocated to either a daily diet containing 5% w/w creatine monohydrate or remained on standard rodent chow. On gestational day 38, dams underwent either control caesarean section where offspring were delivered and recovered immediately, or birth asphyxia whereby the pregnant uterus was excised and placed in a saline bath for 7.5 min, inducing global hypoxia. All offspring were then cross-fostered to a lactating dam. Behavioural assessments were then completed on recovered offspring from neonatal to adolescent/adult ages (postnatal day [PND] 3-41) using the open-field, elevated plus maze, and novel object recognition test.
Results: Offspring that underwent birth asphyxia displayed locomotor deficits and increased anxiety-like behaviour at PND 3-7 in the open-field test (p < 0.05) and impaired novel object discrimination at PND 18 (p < 0.05). Antenatal creatine exposure reduced anxiety-like behaviour irrespective of asphyxia in pups at PND 3, indicating an amelioration of the asphyxia-induced anxiety-like behaviour. In adolescence/adulthood, creatine and asphyxia-exposed offspring showed reduced object exploration (p < 0.0001). Antenatal creatine led to sustained reductions in anxiety-like behaviour in the elevated plus maze at adolescence and increased body weight, regardless of birth asphyxia exposure (p < 0.05).
Conclusion: Antenatal creatine exposure following maternal dietary creatine supplementation decreased anxiety-like behaviour in spiny mice offspring. This change negated behavioural abnormalities caused by birth asphyxia in the neonatal period, though it may have broader influences on long-term emotional and information processing in offspring which warrants further investigation.
Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits, cognitive dysfunction, and stereotyped repetitive behaviors. Regional volume changes are commonly observed in individuals with ASD. To examine volumetric dysregulation across adolescence, the valproic acid (VPA) model was used to induce ASD-like phenotypes in rats.
Method: Regional volumes were obtained via magnetic resonance imaging at either postnatal day 28 or postnatal day 40 (P40), which correspond to early and late adolescence, respectively.
Results: Consistent with prior research, VPA animals had reduced total brain volume compared to control animals. A novel outcome was that VPA animals had overgrown right hippocampi at P40. Differences in the pattern of development of the anterior cingulate cortex were also observed in VPA animals. Differences for the posterior cingulate were only observed in males, but not females.
Conclusion: These results demonstrate differences in region-specific developmental trajectories between control and VPA animals and suggest that the VPA model may capture regional volume changes consistent with human ASD.
Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits, cognitive dysfunction, and stereotyped repetitive behaviors. Regional volume changes are commonly observed in individuals with ASD. To examine volumetric dysregulation across adolescence, the valproic acid (VPA) model was used to induce ASD-like phenotypes in rats.
Method: Regional volumes were obtained via magnetic resonance imaging at either postnatal day 28 or postnatal day 40 (P40), which correspond to early and late adolescence, respectively.
Results: Consistent with prior research, VPA animals had reduced total brain volume compared to control animals. A novel outcome was that VPA animals had overgrown right hippocampi at P40. Differences in the pattern of development of the anterior cingulate cortex were also observed in VPA animals. Differences for the posterior cingulate were only observed in males, but not females.
Conclusion: These results demonstrate differences in region-specific developmental trajectories between control and VPA animals and suggest that the VPA model may capture regional volume changes consistent with human ASD.
Introduction: Neuropsychiatric symptoms following SARS-CoV-2 infection have been described in a substantial proportion of patients, acute, subacute, and chronic. Understanding of the neurological and neuropsychiatric sequelae of this virus is an emerging field of study with rapidly evolving descriptions of its impact on the central and peripheral nervous system.
Case presentation: Here, we report a series of 8 pediatric patients presenting with acute onset neuropsychiatric symptoms following SARS-CoV-2 infection who received comprehensive medical and psychiatric evaluation and treatment in our research-based Neuroimmune Psychiatric Disorders Program. We provide a review of the research available to date regarding potential mechanisms underlying neuroinflammatory consequences of this endemic infection. Opportunities for further investigations of mechanisms, evaluations and impactful treatments following SARS-CoV-2 infection are described.
Conclusion: The pediatric cases presented share acute onset of obsessive-compulsive disorder, psychosis, tics, neurobehavioral and physiological symptoms, with significant response to treatments targeting inflammation in combination with psychiatric and psychological interventions. Ongoing study and identification of this phenomenon of abrupt neuropsychiatric changes following SARS-CoV-2 infection may lead to more effective treatments with potential application to broader populations.
Introduction: Homeobox genes are highly conserved and play critical roles in brain development. Recently, we have found that mammals have an additional fragment of approximately 20 amino acids in Emx1 and a poly-(AL)6-7 in Emx2, compared to other amniotes. It has been shown that Emx1 and Emx2 have synergistic actions in the brain development. These reports raise an interesting issue whether the differences of Emx1 and Emx2 between mammals and non-mammals are concerned with the organization and evolution of amniote pallium.
Methods: Lentiviruses expressing mouse Emx1 and Emx2 (mEmx1/2) with additional fragments were injected into the ventricle of the chick telencephalon at embryonic day 3 to study the effects of mEmx1/2 on the development of chick pallium, whereas injections of lentiviruses containing chick Emx1 and Emx2 (cEmx1/2), no targeted gene insert or saline were as controls. The expressions of reelin, vimentin, GABA and MAP2, neurogenesis patterns for calbindin (CB) and parvalbumin (PV) neurons and the sizes of anterior commissure (AC) were then studied by immuohistochemical staining, and open-field tests were performed to assess locomotor activities and curious or exploratory behaviors of the chicks.
Results: Following the injections of lentiviruses expressing mEmx1/2, the expressions of reelin, vimentin, GABA, and MAP2 increased in most parts of Wulst (W) and mesopallium (M), but not most of nidopallium (N). Neurogenesis patterns for CB and PV neurons changed toward mammalian inside-out one, and the sizes of AC staining for neurofilament were significantly larger. In addition, post-hatchling chicks showed higher rates of passive avoidance after training, but no significant differences in the total distance traveled and the percentage of time spent in the central rectangle, compared to those in the control groups.
Conclusion: The present study indicated that mEmx1/2 had effects on the development of chick pallium, suggesting that they are probably involved in the organization and evolution of amniote pallium.
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