Neuroscience最新文献

Traumatic brain injury (TBI) induces significant neuroinflammation, primarily driven by microglia. Neonatal microglia (NMG) may have therapeutic potential by modulating the inflammatory response of damaged adult microglia (AMG). This study investigates the influence of NMG on AMG function through extracellular matrix (ECM) remodeling and the formation of tunneling nanotubes (TnTs), with a focus on the role of Serpina3n. We established an in vitro TBI model using a 3D Transwell system, co-culturing damaged AMG with NMG. Viral vector transfection was employed to manipulate Serpina3n expression in NMG. Quantitative real-time PCR, Western blotting, and ELISA were utilized to assess inflammatory markers, ECM remodeling proteins, and TnTs-related proteins. Co-culturing with NMG significantly inhibited M1 polarization of AMG and reduced the release of pro-inflammatory cytokines while promoting M2 polarization and increasing the production of anti-inflammatory cytokines. NMG expressed higher levels of Serpina3n, which played a crucial role in reducing Granzyme B, matrix metalloproteinase (MMP) 2 and MMP9 expression, thereby mitigating ECM remodeling. Inhibition of Serpina3n in NMG increased pro-inflammatory markers and decreased TnTs formation proteins, whereas overexpression of M-sec in AMG counteracted these effects. This highlights the importance of TnTs in maintaining microglial function and promoting an anti-inflammatory environment. In conclusion, NMG improve the function of damaged AMG by modulating ECM remodeling and promoting TnTs formation through the action of Serpina3n.

Plethora of research has shed light on the critical role of synaptic dysfunction in various neurodegenerative disorders (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Synapses, the fundamental units for neural communication in the brain, are highly vulnerable to pathological conditions and are central to the progression of neurological diseases. The presynaptic terminal, a key component of synapses responsible for neurotransmitter release and synaptic communication, undergoes structural and functional alterations in these disorders. Understanding synaptic transmission abnormalities is crucial for unravelling the pathophysiological mechanisms underlying neurodegeneration. In the quest to probe synaptic transmission in NDDs, emerging biophysical techniques play a pivotal role. These advanced methods offer insights into the structural and functional changes occurring at nerve terminals in conditions like AD, PD, HD & ALS. By investigating synaptic plasticity and alterations in neurotransmitter release dynamics, researchers can uncover valuable information about disease progression and potential therapeutic targets. The review articles highlighted provide a comprehensive overview of how synaptic vulnerability and pathology are shared mechanisms across a spectrum of neurological disorders. In major neurodegenerative diseases, synaptic dysfunction is a common thread linking these conditions. The intricate molecular machinery involved in neurotransmitter release, synaptic vesicle dynamics, and presynaptic protein regulation are key areas of focus for understanding synaptic alterations in neurodegenerative diseases.

Similar to other brain regions, the neurons in the lateral septum (LS) are of heterogeneous populations. However, their resting membrane potential (RMP) on average is not too far apart. Cells were characterized based on biological markers by using brain slices, as under these in vitro conditions, neurons retain their morphologies. Since the LS neurons are not spontaneously excitable at RMP, the action potentials (APs) were evoked via injections of currents of moderate magnitude. In coronal brain slices of rats, a smaller portion of neurons generated a train of APs of complex nature. In order to define the types of neurons with similar phenotypes, we subsequently used the four lines of td-Tomato transgenic mice. The brains of these mice express the promoter fluorophore td-Tomato and enhanced green fluorescent protein (eGFP). Therefore, recordings were conducted in a targeted manner in neurons expressing glutamic acid decarboxylase (GAD), parvalbumin (PV), somatostatin (SOM), or vasoactive intestinal polypeptide (VIP). Similar spike phenotypes that we refer to as type III, in order to distinguish from AP in principal cells - type I and those in interneurons - type II, also exist in mice, substantiating a similitude among rodents. The type III AP is selectively triggered by Ca²⁺ in GAD and SOM-positive neurons. Conclusions are supported by established pharmacologic tools, nimodipine, TTX, and ZD7288, a selective HCN channel antagonist.Collectively, these observations revitalize our knowledge from pioneering studies with regard to the brain of mammals in general and septal structures in particular.

We investigated proprioceptive acuity for location and motion of a never seen hand-held tool (30 cm long rod) and the accuracy of movements to place tool parts in the location of remembered visual targets. Ten blindfolded right-handed subjects (5 females) reached with the tool held in the right hand to touch the tip and midpoint to the stationary and moving left index-tip, to the right and left ear lobes and to remembered visual target locations. We also tested accuracy of left hand rod reaches to the ear lobes to determine if rod dimensions and control of tool movements experienced during right hand tool use could be used to accurately localize the rod parts when held in the left hand. Errors for right hand-held rod-tip movements to touch the stationary and moving left index-tip averaged only about 1 cm larger than observed previously for right hand movements to touch its index-tip to the left index-tip. The tool-tip was localized with lower mean distance errors (about 1 cm) than the tool-midpoint (5.5-6.5 cm) when reaching to touch the ear lobes with the rod in right and left hands. Right hand reaches to place the tool- tip and midpoint in remembered visual target locations were inaccurate with large overshoots of close targets and undershoots of far targets, similar to previous reports for reaching with the right hand to remembered visual targets. These results support the distalization hypothesis, that tool the tool endpoint becomes the effective upper limb endpoint when using the tool.

Diabetes mellitus is recognized as an important cause of cognitive dysfunction. Ferroptosis plays a key role in diabetic cognitive dysfunction (DCD). Dihydromyricetin (DHM) has promising neuronal protective effects, but it is unclear the mechanism. Here, the effects of DHM on HG-induced neurotoxicity in HT22 cells and its molecular mechanisms were investigated. Our results demonstrated that the viability of HG (125 mmol/L)-induced HT22 cells was significantly decreased. Furthermore, ferroptosis-related indicators, c-Jun N-terminal kinase (JNK)-inflammatory pathway, TNF-α, IL-1β, and mitochondrial morphology were measured. The results show that mitochondria of HT22 cells also showed wrinkled alterations in response to HG treatment. Meanwhile, the levels of glutathione (GSH) and glutathione peroxidase 4 (GPX4) were decreased, accompanied by an up-regulation of malondialdehyde (MDA), Fe²⁺, acyl-CoA synthetase long-chain family member 4 (ACSL4), and reactive oxygen species (ROS), indicating ferroptosis occurred in HG-induced HT22 cells. Furthermore, the levels of p-JNK, TNF-α, and IL-6 were up-regulated in HG-induced HT22 cells. DHM or JNK inhibitor SP600125 reversed these changes in HG-induced HT22 cells indicating that HG-induced neurotoxicity in HT22 cells may be associated with ferroptosis induced by the JNK-inflammatory factor pathway. Meanwhile, JNK agonist Anisomycin could attenuate these effects of DHM. Taken together, our data suggest that DHM can ameliorate HG-induced neurotoxicity in HT22 cells by inhibiting ferroptosis via the JNK-inflammatory signaling pathway. Hence, DHM may represent a novel and promising therapeutic intervention for DCD.

Background: Ischemic stroke represents an urgent need for more efficacious therapies owing to modest effectiveness of current treatment.

Methods: Download data from stroke patients and collect blood samples from clinical patients to analyze phosphatidylinositol-3 kinase catalytic subunit γ (PIK3CG) expression. To establish a brain damage model, oxygen glucose deprivation/reperfusion (OGD/R) was applied to SH-SY5Y cells. Impact of PIK3CG on AMPK/mTOR autophagy pathway was verified treating cells with AMPK activator metformin. Proliferation and apoptosis were identified by CCK8 and flow cytometry.

Results: Differential expression analysis and clinical testing show that PIK3CG is highly expressed in patients. Prolonged ODG/R exposure increased PIK3CG levels, supressed cell proliferation, and induced apoptosis. KEGG pathway analysis implicated PIK3CG in autophagy pathway. Knockdown of PIK3CG supressed OGD/R-induced reductions in cell proliferation and OGD/R-induced increases in apoptosis and expressions of Beclin 1 and LC3 II. Following OGD/R, AMPK phosphorylation was upregulated while mammalian target of rapamycin (mTOR) phosphorylation was downregulated, indicating AMPK/mTOR autophagy activation. Knockdown of PIK3CG opposed metformin-induced rises in Beclin 1, LC3 II and apoptosis along with decreases in proliferation.

Conclusion: PIK3CG knockdown protects neuronal cells by inhibiting AMPK/mTOR autophagy pathway and further inhibiting autophagy.

Heart failure (HF) frequently suffers from brain abnormalities and cognitive impairments. This study aims to investigate brain structure and function alteration in patients with chronic HF. This retrospective study included 49 chronic HF and 49 health controls (HCs). Voxel-based morphometry was conducted on structural MRI to quantify gray matter volume (GMV), and functional connectivity (FC) was assessed with seed-based analysis using resting-state fMRI. White matter microstructure integrity was also evaluated through tract-based spatial statistics employing DTI. Correlations between multimodal MRI features and cognitive performance were further investigated in patients with chronic HF. Patients with chronic HF exhibited significantly reduced regional GMV, white matter microstructure injury (Family wise error correction, p＜0.05), and decreased FC in multiple brain regions involved in cognition, sensorimotor, visual function (Gaussian random field correction, voxel level p＜0.0001 and cluster-level p＜0.01). There was no observed increases in GMV or FC compared with HCs. Decreased GMV showed positive correlations with cognitive performance (r = 0.025-0.577, p = 0.025-0.001), while decreased fractional anisotropy was negatively correlated with anxiety scores (r = -0.339, p = 0.040) in patients with chronic HF. This study revealed that patients with chronic HF exhibited brain structure injury affecting gray matter and white matter, as well as FC abnormalities of brain regions responsible for cognition, sensorimotor and visual function. These findings suggest GMV could serve as a neuroimaging biomarker for cognitive impairments and a potential target for neuroprotective therapies in patients with chronic HF.