Neuroscience最新文献

The nasal microbiome has emerged as a previously underrecognized modulator of neuroinflammation and central nervous system (CNS) homeostasis. Beyond its role in respiratory host defense, this microbial niche is anatomically positioned to directly influence brain physiology through olfactory neuronal pathways, systemic immune signaling, and inter-organ communication within the gut-lung-brain axis. Accumulating evidence indicates that nasal microbiome dysbiosis contributes to blood-brain barrier (BBB) dysfunction, microglial activation, and propagation of neurotoxic protein aggregates, processes implicated in neurodegenerative and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and major depressive disorder. This review synthesizes experimental and clinical studies elucidating key mechanisms by which nasal microbial imbalance may impact CNS pathology, including microbial translocation along olfactory neurons, release of pathogen-associated molecular patterns and inflammatory mediators, extracellular vesicle-mediated signaling, and peripheral immune crosstalk. We further highlight clinical observations linking nasal microbiome signatures with olfactory dysfunction, cognitive decline, and altered inflammatory profiles, particularly in systemic conditions such as sepsis. Despite rapid advances in this field, significant knowledge gaps persist, including the limited availability of longitudinal human cohorts capable of establishing causality, incomplete mechanistic validation in translational models, and insufficient characterization of how environmental exposures and aging reshape the nasal microbiome-brain interface. By integrating current evidence and defining these unmet needs, this review positions the nasal microbiome as a promising source of diagnostic biomarkers and a therapeutic target for modulating neuroinflammation and mitigating neurodegenerative progression.

Beta-thalassemia major (TM) is a severe genetic blood disorder that frequently leads to cognitive impairments in pediatric patients, yet its neurological impact remains insufficiently explored. This study investigates alterations in cerebral gray matter morphology and brain network topology in children with TM and their associations with cognitive performance. High-resolution brain MRI data were processed using FreeSurfer to extract cortical morphological features, from which individual-based Morphological Brain Networks (MBNs) were constructed based on vertex-wise similarity across gray matter regions. A cohort of 27 children with TM and 40 age-matched healthy controls underwent structural network analysis, standardized cognitive assessments, and comprehensive blood testing, including evaluations of hemoglobin and iron concentrations. Results revealed marked structural disruptions in the motor and temporal cortices of TM patients. Network-level analysis further identified topological abnormalities within fronto-parietal regions, suggesting altered structural connectivity patterns that may underlie observed cognitive deficits. Notably, iron overload was significantly correlated with both regional brain changes and impaired network organization, indicating a plausible mechanistic link between systemic iron dysregulation and neural dysfunction. These findings underscore the neurological vulnerability of children with TM and illuminate the structural basis of their cognitive challenges. The study highlights the need to integrate neuroimaging biomarkers with clinical hematological profiles to better understand TM's effects on brain development. Future work should aim to expand these findings through longitudinal designs and larger samples to inform early neurocognitive interventions and optimize treatment strategies for this vulnerable population.

The ability to integrate feedback and flexibly adjust behavior under shifting environmental demands is required to optimize decision-making strategies. Clinical and preclinical data indicate that individuals with stress-related disorders and rodents exposed to chronic stress exhibit impaired behavioral flexibility. The lateral habenula (LHb) has emerged as a key brain region contributing to the effects of stress on cognitive performance. However, the extent to which the LHb is recruited to fine-tune decision-making strategies, as well as the impacts of chronic stress on LHb recruitment during task performance, remain largely unknown. To this end, we used a three-week model of chronic unpredictable stress (CUS) and performed in vivo fiber photometry to investigate Ca²⁺ transients in LHb neurons during an attentional set-shifting task in adult male and female Sprague Dawley rats (n = 7-12/sex/group). We found that CUS exposure did not significantly impair behavioral flexibility. Rather, CUS-exposed rats made fewer omissions and exhibited shorter response latencies compared to controls, suggesting enhanced task engagement. We also observed sex differences in LHb Ca²⁺ activity. In control animals, we found that male rats showed greater inhibition of LHb signal prior to decision making, and greater activation following trial outcome than females. These differences were normalized by CUS, resulting in similar signaling patterns across sexes. Altogether, these findings reveal that chronic stress alters LHb activity in a sex-dependent manner without overtly impairing behavioral flexibility.

Background: Ischemic stroke (IS) is an acute cerebrovascular condition marked by high prevalence, high disability and high mortality rates. Previous studies have indicated that BTB and CNC homology 1 (BACH1) promotes ferroptosis in IS. However, the research on its specific molecular mechanism remains at an early stage.

Methods: To mimic the cell models of IS, SK-N-SH cells were induced by oxygen-glucose deprivation/reoxygenation (OGD/R). Protein levels were tested by Western blot. CCK-8, TUNEL, flow cytometry, and Enzyme-linked Immunosorbent assay were employed to monitor viability, apoptosis, and inflammatory response. Additionally, Fe²⁺, malondialdehyde (MDA), glutathione (GSH) and reactive oxygen species (ROS) levels were detected using relevant kits. Methylated RNA immunoprecipitation (MeRIP) and RIP assays were used to analyze the methylation modification and the binding interactions between molecules. BACH1 mRNA level was examined by qRT-PCR. Finally, an animal model of IS was established using middle cerebral artery occlusion (MCAO) to further validate the in-vitro findings.

Results: Silencing BACH1 alleviated injury in OGD/R-induced SK-N-SH cells. METTL14 and IGF2BP1 cooperatively enhanced BACH1 expression via an m6A-dependent mechanism. Overexpression of BACH1 reversed the protective effects of METTL14 silencing. Moreover, METTL14 inhibited the Nrf2/SLC7A11/GPX4 pathway by stabilizing BACH1. BACH1 downregulation attenuated IS progression in vivo.

Conclusion: The METTL14/IGF2BP1 complex stabilizes BACH1 mRNA through m6A modification. This leads to suppression of the Nrf2/SLC7A11/GPX4 pathway, promotion of ferroptosis, and ultimately exacerbation of IS.

Background: Aging increases vulnerability to cognitive decline, and ultraprocessed diets high in saturated fat may accelerate this trajectory. Although short-term high-fat diet (HFD) exposure is known to impair memory in aged animals, the specific stages of memory most susceptible to short-term HFD remain unclear.

Methods: This study examined how short-term HFD influences anterograde consolidation, retrograde consolidation, and retrieval of long-term fear memory in aged rats. Male F344 × BN F1 rats (22-24 months) consumed chow or three days of HFD provided at distinct times relative to contextual and cued fear conditioning to isolate each memory phase. Importantly, this brief HFD protocol minimizes metabolic disturbances typically produced by longer-term diet manipulation, allowing us to isolate the effects of macronutrient composition on memory processes.

Results: Three days of HFD before or immediately after conditioning significantly impaired contextual and cued fear memory, reflecting disrupted anterograde and retrograde consolidation. In contrast, three days of HFD before retrieval had no effect on memory performance.

Conclusion: These findings demonstrate that short-term consumption of ultraprocessed HFD selectively impairs consolidation while sparing retrieval of hippocampal- and amygdala-dependent memory in aging. These findings are important because identifying the specific memory processes that are disrupted, rather than global memory dysfunction, helps narrow mechanistic targets and informs the development of more precise interventions to mitigate diet-related cognitive decline in aging.

Autonomic dysfunction resulting from damage to the central autonomic network is a common complication of acquired brain injury (ABI). The prefrontal and insular cortices regulate visceromotor autonomic functions, and gastrointestinal dysfunction following ABI may involve impaired autonomic innervation. While repetitive transcranial magnetic stimulation (rTMS) shows potential for studying the top-down control of visceral processes, the mechanisms linking disrupted functional connectivity to autonomic dysfunction and the restorative effects of neuromodulation remain unclear. Sixty-four ABI patients with acute gastrointestinal injury (AGI) were randomized into a control group (CG, n = 32) and an rTMS group (TG, n = 32). Both groups received standard rehabilitation, while the TG additionally underwent 10 Hz rTMS over the left ventrolateral prefrontal cortex (VLPFC-L) (five sessions per week for two weeks). Autonomic function was assessed via heart rate variability (HRV), and whole-brain functional connectivity was measured using 106-channel functional near-infrared spectroscopy (fNIRS). Graph-theoretical network metrics were analyzed. Compared to the CG, the TG showed reduced acute gastrointestinal injury scores, decreased low-frequency (LF) power, a lower low-frequency to high-frequency (LF/HF) ratio, and increased high-frequency (HF) power. Functional connectivity increased in the left ventrolateral prefrontal cortex (VLPFC-L), particularly with the right frontal pole, bilateral premotor cortices, and the left pre-motor/supplementary motor cortex. Global and local network efficiency also improved. These findings indicate that VLPFC-L-targeted rTMS can restore neuroautonomic integration and gastrointestinal function in ABI patients. This study demonstrates the potential of fNIRS and HRV as complementary tools for assessing the effects of neuromodulation on autonomic circuits.

Alzheimer's disease (AD) is a neurodegenerative condition characterised by amyloid-β pathology, neuroinflammation, synaptic dysfunction and cognitive decline. Few pharmacological interventions are available, offering only symptomatic relief, and approval for a number of anti-amyloid biologics is limited, with concerns about safety, cost and efficacy. Here we investigated the effects of 8-10 weeks treatment with liraglutide, NAcGIP[Lys(37)PAL] and Xenin-25[Lys(13)PAL], long-lasting analogues of gut hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and xenin-25, respectively, in the APP/PS1 mouse model of AD. Cognitive function was measured in novel object recognition (NOR) and Morris water maze (MWM) tasks and amyloid burden, gliosis, synapse density and neurogenesis were assessed in brains of APP/PS1 and wild-type mice. AD-associated gene expression analysis was performed to identify potential pathways targeted by treatment. Liraglutide and NAcGIP[Lys(37)PAL] improved cognitive performance in APP/PS1 mice and, along with Xenin-25[Lys(13)PAL], reduced amyloid-β burden in the brain. Liraglutide ameliorated gliosis and all three treatments restored synaptophysin levels. Additionally, Xenin-25[Lys(13)PAL] increased neurogenesis in the dentate gyrus. Numerous AD-associated genes were altered in the brain following treatments. Notably, Serpina3c was upregulated in brains of APP/PS1 mice treated with liraglutide, NAcGIP[Lys(37)PAL] and Xenin-25[Lys(13)PAL], while Map2, Adam9, Lrp8, Casp3, Abca1 and App were downregulated. These results underscore the neuroprotective effects of liraglutide and suggest that NAcGIP[Lys(37)PAL] and Xenin-25[Lys(13)PAL] possess neuroprotective properties. Further investigation of the precise nature of these effects may support development of multi-target therapeutics based on combinations of gut hormone analogues.

Noisy galvanic vestibular stimulation (nGVS) can improve postural stability by delivering subthreshold electrical noise to the vestibular system. However, the frequency-specific effects of nGVS on postural control responses-particularly those involving the center of mass (COM) recovery force and movement strategies-remain unclear. We investigated how different nGVS frequencies affect postural control, estimating COM fluctuations using a rigid pendulum model. Thirty-two healthy adults (mean age, 20.3 ± 1.2 years; 19 females) underwent three interventions: sham nGVS, low-frequency nGVS (LF-nGVS, 0-100 Hz), or high-frequency nGVS (HF-nGVS, 100-640 Hz), each with a 200 µA current (0 µA for the sham). During each 40-s trial, participants stood on a platform with eyes closed and the middle 30 s were analyzed. Inertial measurement units were affixed to the occipital protuberance to capture head kinematics. Postural control was assessed using conventional metrics (e.g., center of foot pressure [COP], COM sway, and head acceleration) and novel indicators of COM recovery force and head acceleration control based on motor strategies. Both LF-nGVS and HF-nGVS significantly reduced several indices, including COP velocity and head angular velocity, compared with sham stimulation. No significant differences were observed between LF-nGVS and HF-nGVS. Head acceleration was significantly correlated with COM recovery force and joint movement strategies in both stimulation conditions. Although the mechanism of neural network activity at different stimulation frequencies requires careful interpretation, these findings suggest that COM recovery and associated motor strategies contribute to nGVS-induced postural improvements, providing insights into its neuromechanistic effects.