Journal of Neuroscience Research最新文献

The prolonged survival of traumatic spinal cord injury (TSCI) patients underscores the need to customize rehabilitative treatment plans according to patients' characteristics, aiming to restore motor function. We conducted a cross-sectional study of two groups with chronic TSCI (short-term group: 11 patients with an injury time of 1–2 years; long-term group: 10 patients with an injury time > 2 years) and 16 controls. Quantitative MRI was used to evaluate structural changes in the upper spinal cord and brain. Compared to controls, both groups exhibited decreased fractional anisotropy (close relationship of the decreased) in the spinal cord, and the long-term group showed reduced spinal cord cross-sectional areas. The short-term group presented increased gray matter volumes (GMVs) in the paracentral lobule, postcentral gyrus, and supplementary motor area, indicating compensatory neural changes, whereas the long-term group exhibited decreased GMV in cerebellar lobule VI, suggesting weakening of the signal received by the cerebellum. Track-based spatial statistics revealed the close relationship of the decreased FA was with the increased radial diffusivity in the long-term group, indicating that demyelination mainly altered the white matter. Correlation analysis revealed that the increased GMV was negatively correlated with the sensorimotor score (r = −0.725, p = 0.018). Additionally, the GMV of cerebellar lobule VI was positively correlated with the sensorimotor score (r = 0.671, p = 0.024). In summary, quantitative MRI identifies structural changes in the brain and spinal cord of patients with chronic TSCI that vary with the time since injury and provide imaging evidence for the development of precise targeted therapies.

Neuroinflammation is a hallmark of various neurodegenerative disorders, yet effective treatments remain limited. This study investigates the neuroprotective potential of a cannabidiol (CBD)-Rich Cannabis sativa L. (CS) extract in a lipopolysaccharide (LPS)-induced neuroinflammation mouse model. The effects on anxiety-like behavior, cognitive function, and locomotor activity were assessed using behavioral tests (open field, elevated plus maze, novel object recognition, and Morris water maze). Antioxidant activity was measured by assaying glutathione (GSH) levels and lipid peroxidation by-products (TBARs). Anti-inflammatory properties were evaluated using quantitative reverse transcription polymerase chain reaction (QRt-PCR) for proinflammatory cytokines (IL-6 and TNF-α), glial fibrillary acidic protein (GFAP), and cannabinoid receptor 1 (CB1) mRNAs in the prefrontal cortex (PFC). Astrocytic bioenergetics were analyzed using extracellular flux assays. Additionally, computational inference with a deep learning approach was conducted to evaluate the synergistic interactions among CS phytocompounds on the CB1 receptors. Compared with synthetic CBD, the CS extract (20.0 mg/kg) demonstrated superior efficacy in mitigating LPS-induced anxiety-like behavior, cognitive deficits, and locomotor impairments. It also significantly mitigated oxidative stress (increased GSH, reduced TBARs) and suppressed proinflammatory cytokines and GFAP mRNAs, indicating potent anti-inflammatory properties. The extract modulated CB1 receptor expression and preserved metabolic homeostasis in cortical astrocytes, preventing their shift from glycolysis to oxidative phosphorylation under neuroinflammatory conditions. Computational modeling highlighted conformational changes in CB1 receptor residues induced by Delta-9-THC that enhanced CBD binding. These findings underscore the potential of CS extract as a therapeutic candidate for managing neuroinflammation and its associated neurodegenerative consequences, warranting further clinical exploration.

Early life stress exposure exerts detrimental effects in adulthood and is a risk factor for psychiatric disorders. Studies addressing the molecular mechanisms of early life stress have primarily focused on hormones and stress circuits. However, little is known on how mitochondria and mitochondrial dynamics (i.e., the orchestration of mitochondrial fission, fusion, mitophagy, and biogenesis) modulate early life stress responses. Here, we used a maternal separation with early weaning (MSEW) paradigm to investigate the behavioral and molecular early life stress-elicited effects in male and female C57BL/6 mice in adulthood. We first applied a behavioral test battery to assess MSEW-driven, anxiety-related and stress-coping alterations. We then looked for MSEW-induced, mitochondria-centered changes in cingulate cortex, hippocampus and cerebellum, as well as in plasma by combining protein, mRNA, mitochondrial DNA copy number (mtDNAcn) and metabolomics analyses. We found that MSEW mice are more anxious, show decreased antioxidant capacity in the cingulate cortex and have higher mRNA levels of the fission regulator Fis1 and the mitophagy activator Pink1 in the hippocampus, indicating a shift towards mitochondrial degradation. Hippocampal mRNA level alterations of apoptotic markers further suggest an MSEW-driven activation of apoptosis accompanied by a dysregulation of purine catabolism in the cerebellum in MSEW mice. Sex-specific analysis revealed distinct MSEW-induced changes in male and female mice at the molecular level. Our work reveals a previously unexplored role of mitochondrial dynamics in regulating early life stress effects and highlights a mitochondria-centered dysregulation as a persistent outcome of early life stress in adulthood.

Central nervous system (CNS) disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and migraines, rank among the most prevalent and concerning conditions worldwide. Despite ongoing research, the pathophysiology of these disorders remains incompletely understood, primarily due to their complex etiology. Current pharmacological treatments mainly focus on alleviating symptoms rather than addressing the underlying causes of these diseases. CNS disorders are marked by impairments in neurocognitive and neuromuscular functions, and cognitive processes like learning and memory. This deterioration not only impacts the quality of life of affected individuals but also places a significant burden on their families. Neuroplasticity is a key property of the nervous system that enables brain repair and functional recovery. However, in CNS disorders, neuroplasticity is often compromised. Neuroplasticity, which is regulated by gene expression, is also modulated by environmental factors and epigenetic mechanisms, thereby reshaping neuronal networks in response to various biological and environmental stimuli and brain function. Importantly, neuroplasticity plays a critical role in repairing the brain, especially in the context of neurodegenerative diseases, where damaged neurons can reorganize and re-establish lost functions. Targeting neuroplasticity mechanisms holds significant potential for developing therapeutic interventions to improve treatment outcomes and prevent CNS disorders. A deeper understanding of neuroplasticity in neurological diseases could open new avenues for enhancing patient quality of life. This review aims to provide a comprehensive overview of synaptic function and the neuroplasticity mechanisms that are disrupted in neurological disorders.

Traumatic brain injury (TBI) is an insult to the brain that impacts neuronal and non-neuronal cells/tissues. The study aimed to understand TBI-induced early changes in the brain and systemic physiology. The male rats were subjected to mild and moderate TBI, where serum and urine metabolic fingerprints of mild TBI rats showed a hypermetabolic response with increased energy metabolites, amino acids, and gut metabolites in serum and increased TCA cycle intermediates in urine. In contrast, the moderate TBI rats showed decreased lactate, pyruvate, amino acids (glycine and leucine) and gut metabolites [trimethylamine N OXIDE (TMAO), choline and acetate] in serum. The urine showed increased pyruvate, creatinine, and allantoin levels. To understand the brain's role in altered metabolic physiology, hypothalamus structure was assessed using diffusion tensor imaging (DTI) and stress levels were observed using serum corticosterone. The injured rats exhibited changes in DTI metrics in the hypothalamus, suggesting a potential disruption in the regulation of the hypothalamus-pituitary–adrenal axis (HPA) axis. These alterations were accompanied by increased TNF-α levels after moderate TBI. The injury induced allostatic overload, accompanied by impaired hypothalamic structure, and metabolic physiology also showed gut microbiome dysbiosis. The gut microbiome showed an increased Firmicutes: Bacteroidetes ratio after injury, with variable gut composition after both injuries. Therefore, the present study provides insight into an interplay between the HPA axis, metabolism, and gut microbiome following TBI. Importantly, this crosstalk between the regulatory systems was different after mild and moderate injury, highlighting the need to assess injury phenotype based on the severity.

Laterality of motor deficits is a hallmark of Parkinson's disease (PD), which is strongly correlated with disease progression. The cerebellum is an important node in the motor-related network in PD. However, the role of the cerebellum in PD lateralization remains unclear. This study enrolled 48 left-dominant-affected PD patients (LPD), 60 right-dominant-affected PD patients (RPD) and 92 age- and sex-matched healthy controls (HCs). We utilized dynamic functional connectivity and co-activation pattern analysis to investigate dynamic alterations of the cerebellum between PD patients and HCs by resting-state fMRI. Pearson partial correlation was used to measure brain-clinical correlations. We revealed two states and five co-activation patterns during the scans. Compared to HCs and RPD, LPD patients more frequently displayed State II and persisted in this state for a more extended period. The mean dwell time (MDT) in State II rose from HCs to RPD and to LPD. The MDT in State II was positively correlated with sleep disturbance in LPD patients. Regarding co-activation patterns (CAPs), LPD and RPD patients were less likely to exhibit CAP2. LPD patients were less likely to demonstrate CAP1 compared to HCs. The CAP1 metrics were positively associated with motor deficits in LPD patients. These results revealed the dynamic alterations of the cerebellum in different dominant-affected PD patients, which were related to motor deficits and sleep disturbances in PD patients. Our findings suggest that the dynamic cerebellar features may be significant factors in the lateralization of PD.

Epilepsy is a common neurological disorder of great importance to patients and society. Sclerosis is associated with neuronal loss and neurodegeneration in specific regions of the hippocampal formation. The hippocampal formation and temporal lobe are not the only regions affected; the chronicity of the disease extends the involvement to other brain regions. Our aim is to investigate the spatial relationship of anatomical structures in both control (CO) and epileptic (EP) subjects using magnetic resonance imaging (MRI) in order to determine changes in epileptic patients compared to healthy anatomical structures. Anatomical landmarks are identified and registered in 3D space to provide a reference for the brain structures; the 3D network is described quantitatively using planar distances, as well as measuring rostrocaudal and Euclidean distances. The planar and rostrocaudal distances are the most remarkable discriminators between CO and EP groups, especially between structures located in and outside the temporal lobe. The study achieves a 100% discrimination between the control group and the epileptic group with the discriminant use of two distances: D_PL, Hpe/Cde and D_RC, As/cae. Finally, discriminates 100% between the three study groups, control group CO, extratemporal lobe epilepsy ETLE and temporal lobe epilepsy TLE, with a total of 12 distances distributed in the three axes of space. This study allows us to hope for a future application, its clinical utility may allow us not only to identify processes (in our case, epilepsy), but also to obtain parameters of the evolution of the disease.