Neuroscience最新文献

Genetic studies have revealed that ARID1B haploinsufficiency leads to autism spectrum disorder (ASD). Given the dynamic development of the brain and behavior, understanding the critical developmental window that influences the onset and severity of ASD-like behavior linked to ARID1B haploinsufficiency is important. Using an Arid1b haploinsufficient mouse model of ASD, we investigated age-dependent ASD-like behaviors at postnatal days 30, 60, and 120. We found that while wild type mice exhibited maturation of social and anxiety-like behaviors over the developmental window, Arid1b haploinsufficient mice showed no progression in the maturation of these behaviors. We also examined oxytocin expression in various brain regions across different developmental stages. Oxytocin mRNA levels in different brain regions were downregulated in Arid1b haploinsufficient mice throughout development and remained reduced with age. Finally, we explored corticosterone expression in Arid1b haploinsufficient mice to determine whether the allostatic regulation between oxytocin and corticosterone is altered in the context of social threat. Both wild type and Arid1b haploinsufficient mice displayed elevated corticosterone levels after social threat. However, Arid1b haploinsufficient mice showed significantly higher corticosterone and lower oxytocin levels than controls, suggesting disrupted allostatic regulation between oxytocin and corticosterone in Arid1b haploinsufficient mice. Our results show that the Arid1b haploinsufficient condition impairs the maturation of social and anxiety-like behaviors associated with ASD, with molecular alterations preceding behavioral deficits in this condition.

Socioeconomic disadvantage shapes brain-mind health by intensifying exposures, resource scarcity, nutritional insecurity, violence, and weak social support, which dysregulate stress and immune systems. These conditions promote allostatic overload, whereby adaptive stress responses become maladaptive, degrading neural circuits for cognitive control and emotion regulation. In parallel, the microbiota-gut-brain axis links contextual adversity and diet quality to inflammation, barrier dysfunction, and neuroendocrine perturbations that further compromise resilience. Converging evidence connects these biological disruptions to structural and functional brain differences and higher risks of depression, anxiety, stress-related syndromes, and later neurodegeneration. While some sociocultural adaptations may bolster cooperation and communal coping, chronic physiological strain undermines durable resilience. This integrative review advances a combined framework, contextual & physiological markers for Individual distress, nested within a brain-mind health perspective, to organise how socioeconomic disadvantage-related exposures are embedded biologically via allostatic and microbiota-gut-brain axis pathways and manifest as social-cognitive difficulties and affective symptoms. We synthesise evidence across behaviour, neural systems, and systemic physiology to identify leverage points for intervention. Priorities include early multi-domain strategies that reduce chronic stressors; strengthen sleep, nutrition, and social cohesion; and test mechanistic interventions (e.g., allostatic regulation, psychobiotic or dietary modulation) within equity-focused, life-course designs. Understanding how contextual and physiological markers interact is essential for designing effective, scalable policies and clinical approaches that mitigate adversity's neurobiological impact and reduce long-term disparities in brain-mind health.

Prior neuroimaging work has shown that people with cerebral palsy (CP) often have visual processing impairments that impact their motor actions. We evaluated if a physical therapy gait training paradigm that incorporated visuomotor tasks has the potential to improve mobility and result in training-related changes in the entrainment of the occipital cortices of people with CP. People with CP (N = 29; Age = 19.9 ± 7.3 years; Gross Motor Classification Score Levels I-III) underwent 24 gait training sessions and completed a comprehensive battery of clinical assessments to quantify their mobility improvements. Magnetoencephalography (MEG) was used to image the cortical activity induced by viewing a 15 Hz flashing stimulus before and after therapy. Neurotypical controls (N = 34; Age = 23.1 ± 3.7 years) were used to gauge the extent of the cortical aberrations and the direction of treatment effects. The group with CP exhibited significantly weaker neural activity in the occipital cortices relative to the neurotypical controls prior to therapy. However, the strength of this event-related synchronization (ERS) increased following therapy. Furthermore, those with a larger change in the strength of the ERS tended to have the greatest improvements in preferred walking speed after therapy. Gait training paradigms that incorporate visuomotor tasks might have the potential to improve mobility, as well as occipital cortical activity in people with CP.

Cerebral infarction (CI) is characterised by a high incidence, significant disability, and increased mortality. Tongqiao Huoxue Decoction (TQHXD), a classical formula, is designed to promote blood circulation and eliminate stasis. We investigated the effects of TQHXD on PC12 cells subjected to oxygen-glucose deprivation (OGD). The results demonstrated that during the early phase of OGD, TQHXD enhanced anaerobic glycolytic flux and increased ATP production, thereby compensating for energy deficits. Concurrently, lactate acts as a signalling molecule that binds to hydroxycarboxylic acid receptor 1 (HCAR1) and activates brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB), which protect PC12 cells from OGD-induced damage and reduce neuronal apoptosis. In the late phase of OGD, TQHXD facilitated the utilisation of lactate as an energy substrate in PC12 cells, generating ATP via lactate dehydrogenase B (LDHB), maintaining cellular energy homeostasis, protecting neurones, and reducing apoptosis. TQHXD modulates glycolysis and lactate metabolism, offering a potential therapeutic strategy for cerebral infarction and a possible sequential intervention approach for targeted therapy.

The prefrontal cortex in primates has a diverse evolutionary history, characterized by distinct phases of development. Granular regions of the orbital prefrontal cortex (PFo) emerged early in primate evolution, while other granular areas, such as the dorsolateral (PFdl) and polar (PFp) regions, evolved later during anthropoid development. This study explored the functional differences among PFp, PFdl, and PFo, focusing on their coding mechanisms, specifically regarding robustness and efficiency. Efficiency was estimated using the 'contrast entropy', defined as the entropy of the neuronal spiking activity normalized by the expected theoretical maximum, whereas robustness was estimated as the synchrony of activity between neurons within the same area. Our investigation revealed that PFp and PFdl show superior information capacity, reflecting efficient coding compared to PFo. Conversely, PFo exhibited higher robustness, suggesting a trade-off relationship between efficiency and robustness consistent with distinct evolutionary stages. The newly incorporated granular prefrontal cortex regions, namely PFp and PFdl, appear to employ a more highly efficient neural code at the expense of reliability, as evidenced by lower robustness.

According to the Pan American Health Organization, more than 300 million people suffer from depression worldwide. Despite the alarming numbers, current drug treatments produce partial results, as they focus on only one pillar of depression: neurotransmitters. Most current medications for depression focus only on stimulating increased levels of neurotransmitters related to feelings of well-being and happiness, such as serotonin and norepinephrine, which, despite providing relief, do not produce such impressive results for patients. A significant and scientifically endorsed point regarding depression is neuroinflammation. The relationship between inflammation in the body and the development or worsening of depression has been strongly reinforced by neuroscientific studies. Studies have also shown that depressed patients have increased levels of inflammatory cytokines. Antidepressants have already demonstrated anti-inflammatory activity, stimulating the production of anti-inflammatory cytokines and reducing the production of oxidative radicals, as in the case of fluoxetine and paroxetine. In depression, P2X7 receptor expression is increased. This receptor is activated, and greater expression produces a depressive phenotype, while its blockade has antidepressant effects. Therefore, we evaluated the in-silico interaction between antidepressants and the allosteric site of the P2X7 receptor. This finding reinforces the functional data in the literature that point to the inhibition of the P2X7 receptor. The molecular docking results showed that drugs containing the amino acids TYR295 and PHE95 are essential for a good interaction with the P2X7 receptor at its allosteric site. Furthermore, this study demonstrated that combining antidepressants with p2x7 receptor antagonists can attenuate neuroinflammation.