Journal of Neuroscience Research最新文献

This study explores whether ultrasound can induce short-term synaptic plasticity (STP)-like effects at the systems level by modulating cortical excitability and sensory responsiveness. We designed a temporally shifted sensory paradigm to test how ultrasound frequency (1, 2, and 4 MHz), inter-stimulus interval (10, 25, and 100 ms), and stimulation order (ultrasound–whisker vs. whisker–ultrasound) affect cortical responses in the rat barrel cortex. Thirty Sprague–Dawley rats underwent an identical experimental protocol. Electrocorticography (ECoG) signals were recorded from the C2 barrel column, and neural responses were assessed by peak amplitude, latency, and power spectral density. Whisker stimulation alone evoked strong cortical responses, significantly greater than ultrasound stimulation. Notably, when ultrasound preceded whisker stimulation by 25 ms, subsequent whisker responses were significantly enhanced, suggesting the existence of a cortical “excitability window” for neuromodulation. This facilitation effect was absent with time intervals of 10 and 100 ms. Mechanistically, ultrasound may modulate membrane tension and activate mechanosensitive ion channels to transiently lower the activation threshold of cortical neurons. These findings reveal that ultrasound can temporally enhance cortical excitability and sensory responsiveness in a frequency- and timing-dependent manner. Our results provide systems-level evidence of STP-like neuromodulation and provide the potential of ultrasound as a noninvasive method for dynamic control of sensory processing.

Repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training (CT) has been explored as a potential novel method to improve response inhibition, but its neural mechanisms remain unclear. This study investigated the effects of rTMS + CT on oscillatory activity across different frequency bands and theta-gamma phase-amplitude coupling during the Stroop task. Sixty healthy participants were randomly assigned to receive four sessions of either active or sham prolonged intermittent theta burst stimulation (iTBS) + CT. Each session involved iTBS over both the right inferior frontal cortex and the pre-supplementary motor area, with participants completing the Stop Signal training task first, followed by the Go/No-Go training task. The Stroop task was administered before and immediately after the intervention while electroencephalography was recorded. There was a significant group effect on the change in beta desynchronization during incongruent trials (t = −2.03, p = 0.048), with a significant decrease observed in the active group (p = 0.03) and no change in the sham group (p = 0.83). Additionally, changes in gamma synchronization differed between groups for congruent trials (t = 2.28, p = 0.03), though neither group showed a significant pre-post change (p > 0.05). Our study suggests that four sessions of iTBS + CT may modulate beta and gamma oscillations during the Stroop task, potentially enhancing motor inhibition and processing speed in response inhibition. These results provide neurophysiological insights into the neural mechanisms through which rTMS + CT may enhance response inhibition.

Dentatorubral-Pallidoluysian Atrophy (DRPLA) is a dominant neurodegenerative disease caused by CAG triplet repeat expansion in ATN1, which encodes the transcriptional co-repressor Atrophin-1. DRPLA features motor, cognitive, and epileptic symptoms and shares pathogenic mechanisms with other polyglutamine (polyQ) disorders, including protein misfolding, impaired autophagy, and transcriptional dysregulation. To understand disease mechanisms, we performed RNA-seq on HEK293T cells stably over-expressing wild-type or pathogenic ATN1. Cells expressing pathogenic ATN1 exhibited a distinct transcriptomic profile, including disruptions in synaptic organization, extracellular matrix remodeling, ion channel expression, and neurotransmission. Several genes tied to neurodevelopmental, neurodegenerative, and oncogenic pathways were fully activated or silenced. Dysregulated pathways also included inflammation, chromatin remodeling, stress responses, and redox imbalance. Heat shock protein expression changes suggested proteotoxic stress and impaired protein quality control, with some findings conserved in a previously reported Drosophila melanogaster model of DRPLA. The transcriptomic signatures that we describe here expand understanding of the normal functions of ATN1 and the biology of disease of DRPLA.

The amino acid neurotransmitter gamma-aminobutyric acid (GABA) reportedly acts by unidentified ventromedial hypothalamic mechanisms to suppress hypoglycemia-associated counterregulatory endocrine function in male rats. Present studies addressed the premise that GABAergic transmission of ventromedial hypothalamic nucleus (VMN) origin may regulate dorsomedial VMN (VMNdm) growth hormone-releasing hormone (Ghrh)/steroidogenic factor-1 (SF-1) neuron counterregulatory signaling to control this hormone outflow. VMN glutamate decarboxylase-2 (GAD2/GAD₆₅) gene knockdown increased basal but inhibited insulin-induced hypoglycemia (IIH)-associated augmentation of corticosterone and glucagon secretion, while suppressing growth hormone secretion regardless of glucose status. Multiplex qPCR analysis of laser-catapult-microdissected VMNdm Ghrh-immunoreactive neurons showed that GAD2 siRNA pretreatment intensified IIH-associated upregulation of mRNAs that encode the counterregulatory-enhancing neurochemicals nitric oxide and glutamate, and exacerbated hypoglycemic downregulation of GAD1, GAD2, and SF-1 transcription. VMN GAD2 gene silencing augmented hypoglycemic enhancement of Ghrh neuron 5′-AMP-activated protein kinase alpha-1 and alpha-2 gene expression. VMN GAD2 gene knockdown exacerbated both positive lactate receptor and negative estrogen receptor transcriptional reactivity to IIH. Study outcomes provide novel evidence for bidirectional, glucose status-specific VMN GABAergic control of corticosterone and glucagon secretion in male rats, which is not documented in the other sex. Data verify GABA regulation of VMN dorsomedial Ghrh neuron metabolic and hormonal signal reception, energy screening, and counterregulatory neurochemical release. Further effort is needed to characterize the impact of GABA-dependent neurotransmission by this discrete VMN neuron population on neural circuitries that govern glucose homeostasis.

Propofol, an anesthetic known for its safety, efficacy and neuroprotective properties, has potential novel antidepressant effects. However, its specific mechanisms still require further elucidation. Presently, we established a learned helplessness (LH) depression model to investigate the effects of propofol treatment on depression-like impairment. Thirty adult male C57BL/6j mice were randomly divided into three groups: control group (CON), model group (LH), and propofol group (PRO), with 10 mice per group. Behavioral analyses were conducted using weight measurement, sucrose preference test (SPT), forced swim test (FST), tail suspension test (TST), and Morris water maze test (MWM). Subsequently, HE staining was performed to examine pathological changes in the hippocampal region. Western blotting was conducted to assess changes in Notch signaling pathway components, synaptic plasticity-related proteins, and proteins in the glutamate system. Immunofluorescence was used to detect expression changes of NICD, SYP, and DCX. Hippocampal glutamate concentration was determined using a glutamate assay kit. Consequently, stressed mice exhibited pronounced depressive behaviors and decreased spatial learning and memory, accompanied by significant neuronal death in the dentate gyrus of the hippocampal region and reduced levels of neuronal regeneration as well as synaptic plasticity. Additionally, glutamate reuptake function was impaired in depression, manifested specifically as increased glutamate concentrations in the hippocampal region and neuronal glutamate transmission levels. Meaningfully, propofol upregulated Notch signaling pathway activity and improved glutamate reuptake function significantly resulting in enhanced adult hippocampal neurogenesis and synaptic plasticity. These findings demonstrated the effectiveness of propofol as a potential antidepressant and contributed to discovering novel antidepressant drugs.

Traumatic brain injury (TBI) results from external mechanical forces causing brain dysfunction. Dysregulated microRNAs (miRNAs) have been implicated in TBI pathophysiology, but the role of miR-598-3p remains unclear. This study aimed to evaluate the diagnostic and prognostic value of miR-598-3p in TBI and explore its regulatory effects on inflammation in an LPS-induced microglial injury model. Serum miR-598-3p levels were measured via RT-qPCR in 137 TBI patients and 120 controls. ROC curves assessed its diagnostic and prognostic utility. TBI severity was classified by Glasgow Coma Scale (GCS) scores, and outcomes were evaluated using the Glasgow Outcome Scale (GOS). In vitro, LPS-treated BV2 microglia were transfected with a miR-598-3p inhibitor to analyze inflammatory cytokine levels. miR-598-3p expression was significantly elevated in TBI patients versus controls (p < 0.001) and increased progressively with injury severity. ROC analysis demonstrated high diagnostic accuracy for distinguishing TBI severity (AUC = 0.892/0.905) and predicting poor prognosis (AUC = 0.891, sensitivity = 83.33%, specificity = 90.36%). High miR-598-3p expression correlated with elevated Marshall grades, neural injury markers (S100B, GFAP), and pro-inflammatory cytokines (IL-6, TNF-α). Multivariate analysis identified miR-598-3p as an independent risk factor for poor outcomes (OR = 5.03, p < 0.01). miR-598-3p inhibition attenuated LPS-induced IL-6/TNF-α secretion (p < 0.01). Serum miR-598-3p demonstrates clinical utility as a biomarker for TBI diagnosis, severity grading, and prognostic evaluation. Its observed association with amplified microglial inflammatory responses suggests a potential mechanism involving regulation of neuroinflammation pathways.