Neuroscience最新文献

To date, the burden of alcohol-related seizures is increasing, with an unexplored etiological complex, and the psychopharmacological interplay remains significantly scarce. In this study, we developed an experimental approach to investigate the contrasting impact of alcohol on pentylenetetrazol-induced seizures and the effects of diosgenin, a phytosteroid agent with neuroprotective effects. After 7 days of binge alcoholism with ethanol (2 g/kg, oral gavage) in male mice, they were subjected to maximum and sub-convulsive pentylenetetrazol-induced seizures concomitantly with diosgenin (25 and 50 mg/kg, p.o.) or diazepam (3 mg/kg, p.o) treatments from days 8-14. The interaction between ethanol and pentylenetetrazol-induced seizures was investigated, along with behavioral comorbidities, hypothalamic-adrenal-pituitary-axis (HPA-axis), neurochemical and neurotrophic dysfunctions, oxidative stress, and neuroinflammation in the hippocampus, prefrontal-cortex, and striatum. Ethanol-exacerbated pentylenetetrazol-induced seizure and frequency, characterized by rearing with myoclonic jerks, and clonic-tonic convulsions. It increased anxiety, depressive behavior and impairs spatial working memory, influenced by heightened alcohol preference and corticosterone levels, which were normalized by diosgenin. Concomitant ethanol administration exacerbated reductions in GABAergic-dependent glutamic-acid decarboxylase and increased glutamate levels associated with pentylenetetrazol-induced seizures, alongside depletions of serotonin and brain-derived neurotrophic factor in the hippocampus, prefrontal-cortex, and striatum. Among others, diosgenin, compared to ethanol-pentylenetetrazol exacerbation, reduced levels of myeloperoxidase, TNF-α, and IL-6, nitrite and malondialdehyde in the hippocampus, prefrontal-cortex, and striatum while increasing IL-10 cytokine and antioxidant substrates (superoxide-dismutase, glutathione, and glutathione-transferase). These findings suggest that alcoholism exacerbates seizures across brain regions, involving neurochemical imbalance, HPA-axis dysfunction, oxidative stress, and neuroinflammation, which are reversible by diosgenin.

Coordinated lateralized movements are critical for natural orienting behaviors, but their neural bases remain poorly understood. The deep superior colliculus (dSC) integrates a wide range of inputs to select targets for orienting movements and coordinates downstream activity to initiate and execute movement. The substantia nigra pars reticulata (SNr) is thought to disinhibit dSC to facilitate movement, but much remains unknown about the relationship between SNr activity, dSC activity, and movement. We recorded from both regions using high-density probes in head-fixed mice performing directional orienting tasks. We found that dSC and SNr activity reflected task variables preceding and throughout movement. However, the direction-dependence of dSC activity was weaker than in other orienting behaviors, and the relationship between movement-related dSC and SNr activity was inconsistent with disinhibition of dSC determining the initiation or direction of movement. Analyses of similar data curated by the International Brain Laboratory yielded consistent results. These findings suggest diverse roles for modulatory input from SNr to dSC in shaping motor behavior.

Glutamate accumulation linked to Parkinson's disease (PD) pathogenesis. While glutamate chemical exchange saturation transfer (GluCEST) imaging has been applied in various CNS disorders, its utility in PD remains underexplored. This study investigated the clinical relevance of dentate nucleus and cerebellar hemisphere glutamate levels across PD motor subtypes. We enrolled 36 resting-tremor predominant PD (PDRT), 33 akinetic-rigid predominant PD (PDAR), and 40 healthy controls (HCs). GluCEST data were quantified via magnetization-transfer-ratio asymmetry (MTR_asym) analysis, with four regions of interest (ROIs) manually delineated. Cerebellar volumetry was derived using the SUIT atlas. Results demonstrated significantly elevated MTR_asym values in the dentate nucleus and cerebellar hemisphere of PDRT patients (*p*<0.05), indicative of increased glutamate concentrations. Concurrently, PDRT exhibited reduced cerebellar volumes compared to HCs, whereas PDAR showed no significant volumetric differences. These findings establish GluCEST as a sensitive, non-invasive biomarker for cerebellar glutamatergic pathology in PD. The subtype-specific metabolic disturbances imply distinct etiological mechanisms underlying tremor-dominant and akinetic-rigid phenotypes.

This study aims to explore the distinct effects of left and right prefrontal Transcranial Photobiomodulation (tPBM) on brain functional networks and to quantify the neuromodulation responses of functional brain networks constructed from EEG data under stimulation from heterolateral targets. 18 healthy, young, right-handed participants with no history of neuropsychological disorders participated in two tPBM sessions over a 3-week period. Resting-state EEG data were collected before and after tPBM. Functional connectivity, measured by coherence, and graph theory analysis (GTA) were applied to delta, theta, alpha, and beta bands to assess both global and local network topology. 810 nm tPBM targeting the right prefrontal cortex significantly enhanced long-range functional connectivity in the delta, theta, and beta bands. It increased the global clustering coefficient in the delta band and decreased it in the alpha band. In contrast, left prefrontal tPBM mainly influenced theta band connectivity, increasing the global clustering coefficient in the delta band and reducing nodal clustering in the right central region in the theta band and the right temporal region in the beta band. The findings reveal that both left and right prefrontal 810 nm tPBM induce significant neurophysiological changes in brain network topology. However, the neuromodulation effects differ across brain functional connectivity, as well as global and local network topology levels. The findings in this study provide novel insights into the effects of heterolateral target tPBM stimulation on the brain network and suggest that left prefrontal tPBM could be a potential choice for personalized treatment of neuropsychiatric disorders.

Currently, the accepted mechanism of noise-induced hidden hearing loss (NIHHL) is cochlear synaptopathy which disrupts afferent synapses of the cochlear inner hair cells; however, the molecular basis underlying the cochlear synaptopathy remains unclear. In this study, adult mice were subjected to single or twice moderate noise exposure (the 1st , and 2nd NE, respectively) . The results showed that mice after the 1st NE exhibited a temporary threshold shift (TTS) that recovered within two weeks, while immunofluorescence staining revealed loss of ribbon synapses. After 2nd NE, by contrast, permanent threshold shifts were observed, with more severe loss of ribbon synapses. Furthermore, we found that ERK1/2 was phosphorylated (p-ERK1/2) in the cochlea following both the 1st and 2nd NE, and the peak of p-ERK1/2 emerged earlier after the 2nd NE. Administration of the ERK1/2 inhibitor SCH772984 significantly restored hearing compared with controls. Taken together, our findings demonstrate that noise exposure activates ERK1/2 phosphorylation in the cochlea, leading to hearing loss, and indicate that activation of the ERK1/2 pathway may represent a cellular mechanism underlying NIHHL.

LGBTQIA+ (lesbian, gay, bisexual, transgender, queer, intersex, asexual, and related identities) individuals in science face unique career challenges. We surveyed a large sample (N = 428) of neuroscientists, uniquely capturing a diverse international population (hundreds of participants from both Europe and the USA; more than 60 transgender participants). In the USA compared to Europe, we found higher institutional support and higher likelihood of being out of the closet in academic settings. However, participants based in the USA also reported more negative workplace experiences. A concerning 15% of the participants reported experiencing harassment at their workplace. Thematic analysis of qualitative responses showed that reasons for not being out varied by group; for example, asexual people were more likely to mention a lack of understanding, while transgender people reported safety concerns. The majority of participants (67.3%) felt that legislation affected decisions within their scientific career, with most of these participants reporting moving away from locations unsupportive of LGBTQIA+ individuals, or forgoing career opportunities in certain locations. Overall, we show differential experiences of neuroscientists between the USA and Europe, as well as between identities. While our results demonstrate the challenges many LGBTQIA+ individuals in neuroscience face, they also put forward actionable recommendations for institutions which could vastly improve the lives and careers of LGBTQIA+ neuroscientists.