Developmental Neurobiology最新文献

The detrimental effects of prenatal stress (PS) on offspring's neurological and behavioral outcomes are well documented. However, strategies to mitigate these effects are underexplored. This study examines whether prenatal zinc supplementation and treadmill exercise can modulate PS-induced cognitive impairments and neurobiological markers in young and adult male rat offspring, leveraging the established neuroprotective potential of both physical activity and zinc. Pregnant rats were divided into five groups: control, stress, stress + exercise, stress + zinc, and stress + exercise + zinc, with all rats except the control group subjected to restraint stress (gestational days 15–19). Pregnant rats in the exercise groups underwent forced exercise, whereas those in the zinc groups received oral zinc sulfate throughout the pregnancy. At postnatal days 30 and 90, the cognitive function of male offspring was evaluated using the Morris water maze (MWM) test, and the hippocampal gene expression levels of caspase-3, brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) were measured using reverse transcription–polymerase chain reaction (RT-PCR). PS impaired cognitive functions, increased caspase-3 expression, and decreased BDNF and GFAP expression levels in adult rats. Prenatal exercise was found to mitigate PS-induced cognitive deficits primarily through enhancing GFAP expression, whereas prenatal zinc improved PS-induced cognitive impairments mainly through reduced caspase-3 and increased BDNF expression. The combined effect of exercise and zinc was not additive on cognitive functions and biomarkers. Physical activity may alleviate PS-induced cognitive deficits by modulating astrocytic factors, whereas zinc may exert its effects by inhibiting apoptosis via a BDNF-dependent pathway. Further targeted research is necessary to confirm these relationships.

Epilepsy refers to a diverse group of neurological pathologies, coupled with a significant worldwide impact. Azilsartan, an angiotensin receptor blocker, is broadly applied as an antihypertensive medication. Considering that the neuroprotective potential of Azilsartan has been newly documented, our work was committed to characterizing the association of Azilsartan with epilepsy and its possible mechanism. First, mice hippocampal neuron (HT-22) cells were exposed to kainic acid (KA) with or without Azilsartan treatment. Cell Counting Kit 8 (CCK8) method assessed the viability of KA-treated HT-22 cells. Flow cytometry assay was employed to detect cellular apoptotic capacity. DCF-DA fluorescent staining, JC-1 probe, and related assay kits were used to estimate mitochondrial oxidative stress. Western blotting examined the expression of Sirtuin 3 (Sirt3), superoxide dismutase 2 (Sod2), and apoptosis-related proteins. Additionally, Sirt3 was silenced to analyze whether the protective effect of Azilsartan on KA-induced damage of HT-22 cell damage was achieved by regulating Sirt3. Results indicated that KA intervention concentration-dependently triggered the viability loss, apoptosis, and mitochondrial damage in HT-22 cells. Azilsartan treatment protected against KA-induced HT-22 cell injury by elevating the viability, reducing the apoptosis, and attenuating mitochondrial damage. Besides, Azilsartan administration activated Sirt3 and Sod2 expression in KA-stimulated HT-22 cells, and Sirt3 depletion partially blocked the impacts of Azilsartan on Sirt3/Sod2 pathway, mitochondrial damage, viability, and apoptosis in HT-22 cells exposed to KA. Collectively, Azilsartan might act as a neuroprotective agent in treating epilepsy through the activation of Sirt3/Sod2 pathway.

Hypoxia, or low oxygen levels, is linked to several pathological disorders, including retinopathies. Retina being a metabolically active tissue, low oxygen levels resulted in retinal degradation. The developmental perspective of hypobaric hypoxia (HBH)-induced eye development remains elusive. Drosophila is used as our model organism to investigate the impact of HBH on eye development and alpha-tocopherol as a potential inhibitor. To induce the hypoxic condition, we exposed the Drosophila to hypobaric pressure (120 mbar). Hypoxia induces eye defects in different developmental stages of Drosophila as revealed by histological staining. Biochemical estimation disclosed the presence of reactive oxygen species (ROS) during hypoxia, which led to cellular injury and DNA damage. Quantitative PCR reveals the upregulation of Puf, Wge, and Twr genes and the downregulation of Rh1 and Rh6 involved in eye development. All these defects are brought back to normal levels after treatment with alpha-tocopherol. This research provides a foundation for understanding ocular developmental problems caused by oxygen deprivation and alpha-tocopherol as a crucial therapeutic approach to the treatment of HBH.

The term “neurodiversity” refers to the natural heterogeneity in human neurological functioning, which includes neurodevelopmental differences and other mental health conditions (e.g., autism spectrum disorder [ASD], attention-deficit hyperactivity disorder [ADHD], dyslexia, bipolar disorder, schizophrenia, and depression). This new viewpoint has significant consequences for the future of medicine, specifically in psychiatry, neurology, and neurodevelopmental medicine, as it undermines established notions of these conditions as disorders/diseases that may be healed or corrected. The neurodiversity approach, on the other hand, acknowledges these divergences as natural variations, calling for tailored support and interventions that accommodate individual needs. Neurodiversity could impact current medical perspectives by supporting a shift from pathology to identity. Rather than focusing on the difficulties associated with a specific ailment, the neurodiversity approach stresses the strengths and distinct perspectives that come with neurodivergent identities. This shift has significant consequences for research and therapy by fostering the development of innovative treatments aimed at increasing quality of life and improving functional results. This new perspective advocates including neurodivergent people in all sectors of society, including research, clinical practice, and policymaking, by recognizing, accepting, and integrating natural variances in brain functioning. In this article, we review the development of the neurodiversity movement and propose “The Neurodiversity Framework in Medicine,” which challenges traditional views by recognizing neurological differences as natural variations, advocating for inclusive, person-centered approaches in healthcare.

Owing to the high prevalence of gastrointestinal dysfunction in patients, the gut–brain axis is considered to play a vital role in neurodevelopment diseases. Recent pieces of evidence have pointed to the usage of antibiotics at an early developmental stage to be a causative factor in autism due to its ability to induce critical changes in the gut microbiota. The purpose of the study is to determine the neuroprotective effect of capric acid (CA) on autism in antibiotic-induced gut dysbiosis in rodents. In this study, the effect of CA was observed in penicillin V (31 mg/kg, p.o.) exposed animals by evaluating their autism-like behavioral and biochemical parameters. The establishment of gut dysbiosis was confirmed by 16 RNA sequencing, and behavioral tests were performed. Subsequently, oxidative stress, cytokine levels, and mitochondrial complex activities in the hippocampus and prefrontal cortex were analyzed. It was observed that the administration of penicillin V during the perinatal period produced gut dysbiosis and long-lasting changes in social behavior with symptoms of anxiety and depression and impaired learning and memory. Treatment with penicillin V also produced oxidative stress, mitochondrial dysfunction, and inflammation in the hippocampus and prefrontal cortex. Treatment with CA produced a positive effect on the alterations with maximum effects evident at 400 mg/kg, p.o. through amelioration of behavioral as well as biochemical changes. The current study concluded that CA could act as a likely candidate for the treatment and management of autism via modulation of gut dysbiosis-induced neurobehavioral parameters, oxidative stress, mitochondrial dysfunction, and inflammatory markers.

Observational studies have found that elevated serum homocysteine (Hcy) levels during pregnancy may be associated with the occurrence of neural tube defects (NTDs). However, the effect of Hcy on fetal neural development and its underlying molecular mechanisms remains unclear. To uncover the molecular mechanism, we analyzed the serum Hcy concentration in pregnant women with normal and abnormal pregnancy outcomes and treated zebrafish model embryos with high Hcy. Our findings indicate that elevated serum Hcy levels during pregnancy are associated with adverse pregnancy outcomes. Using the zebrafish model and transcriptome analysis, we found that high Hcy levels led to developmental neural malformations in embryos and affected the expression of key genes at various stages of neural development. Interestingly, deep transcriptome analysis showed that dysregulated heat shock proteins (HSP) might play a key role in high Hcy-mediated alterations in neural development. Importantly, the inhibition of HSP significantly restored the embryonic neuroteratogenic effects induced by high Hcy levels in the zebrafish model. In summary, our findings provide a novel molecular pathogenic mechanism in which ectopic HSP is associated with neural development defects caused by high Hcy levels, suggesting potential prevention and targeted therapies for high Hcy level-related NTDs during pregnancy.