Journal of Neuroscience Research最新文献

Sudden infant death syndrome (SIDS)—the sudden and unexplained death of a seemingly healthy infant, < 1 year old—may be associated with abnormalities in the brain regions that underlie breathing and arousal during sleep. While post-mortem studies suggest abnormalities in SIDS infants' brainstems, there are no studies of these infants' brainstem function before death. One way to assess the function of the brainstem is with auditory brainstem response (ABR), a routine hearing-screening method that noninvasively measures the brainstem's response to sound. We hypothesized that anomalies in newborns' ABR measures may predict SIDS. We integrated two secondary datasets and examined ABRs of newborns who later died of SIDS (n = 11) compared to a normative sample (n = 198,990), using existing archived records of neonatal ABR results from a sample of newborns born in Florida. As hypothesized, infants who died from SIDS were more likely than non-SIDS infants to have abnormal ABRs as newborns. Children who died of SIDS appeared to have shorter latencies to the trough that follows peak V in the left ear than children without SIDS. However, our expert-rated data failed to replicate this finding, suggesting it is unlikely to reflect a true effect. Understanding the association between SIDS and ABR may facilitate more accurate identification of an infant's risk for SIDS at birth, enabling increased monitoring, which may facilitate interventions and improve survivorship.

Perioperative neurocognitive disorder (PND) is common in older patients after anesthesia and surgery, significantly increasing morbidity and mortality. However, the role of astrocytes in its pathogenesis remains limitedly understood. Here, we analyzed 9976 and 9484 single-cell transcriptomes from hippocampal cells of aged mice undergoing PND surgery or sham operation, focusing on astrocytes. We identified 13 distinct clusters corresponding to nine cell types, including astrocytes, microglia, neurons, oligodendrocytes, and other relevant cell populations. Specifically, five astrocyte subclusters were identified, with cluster 0 being the most abundant. Its proportion decreased by 5.51% in the PND surgery condition, showing the largest difference between the groups. Functional enrichment analysis revealed that astrocytes are involved in crucial neurodevelopmental processes and pathways associated with nervous system development and synaptic regulation. Pseudotime analysis placed cluster 0 at the early stage of differentiation, suggesting it as a key responsive population. Gene co-expression network further identified modules with peak activity in cluster 0. By intersecting cluster 0 markers with differentially expressed genes (DEGs) and applying machine learning methods, including LASSO, XGBoost, and Random Forest, we pinpointed four feature genes Dbp, PISD, Id4, and Tsc22d3 with differential expression patterns between surgery and control conditions. Transcription factor activity analysis highlighted distinct regulatory networks in astrocytes, providing insights into their functional differences in response to PND surgery. These findings offer a detailed aged hippocampal landscape of astrocyte dynamics and intercellular communication, contributing to our understanding of neuroinflammation and cognitive dysfunction following surgical stress.

Focused ultrasound (FUS) holds potential to inhibit peripheral nerves to manage pain. We previously found FUS parameters resulting in changes to nerve structure and reversible increased mechanical withdrawal threshold as well as reversible inhibition of motor and non-pain sensory fibers. However, as behaviors were only followed for 4 weeks and structure for 2 weeks, the duration of increased thermal withdrawal latency and changes to nerve structure were undetermined. We investigated the duration of increased thermal withdrawal latency and nerve structure alterations after FUS application in an acute pain model. FUS was applied directly to the rat sciatic nerve prior to hindpaw (HP) incision; animal behaviors (thermal and mechanical nociceptive thresholds, HP extension and flexion) were assessed for 12 weeks and nerve structure was assessed for 28 weeks. The primary outcome was the change in HP thermal withdrawal latency. Secondary outcomes were the changes to sciatic nerve structure and HP mechanical withdrawal threshold, extension, and flexion. Compared with controls, after FUS application, animals had increased thermal nociceptive thresholds until week 9, increased mechanical nociceptive thresholds until week 2, decreased HP motor response until week 3.5, and decreased HP plantar sensation until week 4. Nerve ultrastructure changes may have persisted until week 24. In this new longer-term follow-up study, after invasive FUS application to the sciatic nerve in a rodent model of acute incisional pain, we determined the duration of changes to thermal hyperalgesia, mechanical hyperalgesia, motor, and non-pain sensory responses, and changes to nerve structure.

Cortical malformations, including microgyria, are often associated with neurodevelopmental comorbidities such as epilepsy and cognitive impairments in humans. To investigate how early cortical disruption leads to persistent behavioral impairments, we employed a neonatal neocortical focal freeze lesion (FFL) model of polymicrogyria in male Wistar rats. Unilateral cortical lesions were induced at postnatal day 0 (P0), and molecular changes in hippocampal gene expression (glutamatergic signaling: Grin1, Grin2a, Grin2b, Gria1, Gria2; neuroinflammation: Nlrp3, Il1b, Il1rn; glial markers: Gfap, Aif1; neurotrophic factors: Bdnf, Fgf2) were analyzed at P21. Behavioral outcomes, including locomotor activity, exploratory behavior, anxiety-like behavior, social interaction, and recognition memory, were assessed in adulthood (P70–P90). Neonatal cortical lesions induced subregion-specific alterations in hippocampal gene expression: Grin2b and Gria1 expression decreased in the ipsilateral dorsal hippocampus, while Grin2a, Bdnf, and Fgf2 increased in the contralateral ventral hippocampus. These molecular changes were associated with subsequent cognitive deficits (impaired recognition memory) and emotional dysregulation (heightened anxiety-like behavior) in adult rats, alongside reduced exploratory activity. Basic motor functions and sociability remained unaffected, and seizure susceptibility (assessed via maximal electroshock threshold) was unchanged, highlighting the specificity of the observed impairments. Our findings suggest a potential mechanistic link between early-life cortical malformations with microgyrus formation, dysregulation of hippocampal synaptic plasticity and neurotrophic signaling, and persistent neurobehavioral deficits. These results underscore the translational relevance of the freeze lesion model for studying the neurodevelopmental trajectory of cortical malformation-related comorbidities.

Temporal lobe epilepsy (TLE) is a focal epilepsy extensively examined through advanced neuroimaging techniques to elucidate its pathophysiological mechanisms. This study investigates the differences in dynamic brain activity and gene expression in TLE patients. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 60 TLE patients and 30 healthy controls (HC). Dynamic amplitude of low-frequency fluctuations (dALFF) was employed to identify regions with dALFF variance differences, which were then designated as regions of interest (ROIs). Co-activation patterns (CAP) was constructed to compare brain dynamic changes. Pearson's correlation analysis and pathway enrichment analysis were used to explore the potential molecular mechanisms associated with atypical neural dynamics in TLE. Five CAP states were identified from the rs-fMRI data. Compared to HC, TLE with cognitive normal (TLE-CN) and TLE with cognitive impairment (TLE-CI) patients exhibited atypical state-specific temporal characteristics, including number of states (counts), fraction of time, persistence, resilience, and transition probability (TP) between states. Importantly, dynamic indicators of CAP states were significantly correlated with cognitive performance. Furthermore, 2752 genes were significantly associated with atypical dynamic brain states in TLE, with these genes primarily enriched in synapse-related pathways. This study offers novel insights into atypical neural dynamics from a temporal perspective. The brain network dynamics defined by CAP analysis deepen our understanding of the neurobiological underpinnings of TLE and TLE-CI, revealing a link between atypical neural architecture and gene expression in TLE.

To assess the impact of SK channel agonists on seizure-like events (SLEs) in various seizure models in slices of the temporal cortex obtained from pharmacoresistant patients. SLEs were triggered by applying 4-aminopyridine (100 μM) to slices of the entorhinal cortex taken from both normal and pilocarpine-treated rats. Additionally, SLEs were induced in slices of the temporal cortex obtained from individuals who had undergone epilepsy surgery. In the case of human slices, SLEs were also provoked by increasing potassium levels along with the administration of either 4-AP (100 μM) or bicuculline (50 μM). The activation of SK2/3 channels by the compound CYPPA (n = 8) effectively prevented SLEs in slices from the brains of normal rats, pilocarpine-treated rats (n = 8), and in human cortex slices (n = 9) when SLEs were triggered by 4-AP. In human temporal cortex slices, CYPPA also demonstrated efficacy in preventing SLEs induced by an elevation in potassium concentration combined with bicuculline application (n = 5). SKA-31, exhibited efficacy in slices from normal rats (n = 8), rats treated with pilocarpine (n = 8), and in human slices (n = 7) when SLEs were provoked by 4-AP. However, its effectiveness was limited when applied to human tissue slices exposed to bicuculline and elevated potassium levels. The SK1 channel activator GW-542573X displayed only moderate anticonvulsant effects in the models under investigation. SK2 channels showed the highest effectiveness across the different epilepsy models. Sensitivity to the SK3 channel activator was found to be more pronounced compared to the other two activators studied.