European Journal of Neuroscience最新文献

Despite age-related declines in the structure and function of auditory and language-related regions, many older adults retain a relatively preserved ability to understand speech in noisy environments. However, the neural mechanisms supporting this ability remain unclear. In this study, 30 older adults (59–71 years) with normal hearing listened to narratives spoken by a separate group of speakers at varying noise levels, with their neural activity recorded using functional near-infrared spectroscopy (fNIRS). Speaker-listener neural coupling analysis revealed that older listeners' neural activity across broad brain regions, including classical language regions and the prefrontal cortex, was coupled with the speaker's speech-production-related neural activity. Compared to younger listeners, older adults exhibited stronger prefrontal neural coupling, which was stably integrated with language-region coupling across noise levels. Crucially, as noise levels increased, prefrontal neural coupling became more strongly correlated with comprehension performance. These findings elucidate the neural mechanisms supporting natural speech-in-noise processing in the aging brain, highlighting the compensatory involvement of the prefrontal cortex in facilitating speech-in-noise comprehension in older adults and indicating it as a potential target for neuromodulatory and cognitive interventions to promote successful aging.

Anxiety is a future-oriented mood state that consists of a complex cognitive, affective, physiological and behavioural response system that prepares individuals for perceived or anticipated threats. Although the neural circuits underlying anxiety behaviours have been extensively studied, how inflammatory factors influence anxiety and the molecular links between them remains poorly understood. To gain novel insights into these mechanisms, we investigated the role of fam19a5a, a zebrafish ortholog of the human FAM19A5 gene, which encodes a secreted peptide, in anxiety-like responses. Gene expression analyses revealed widespread fam19a5a expression in anxiety-associated brain regions, including the septum, pallial amygdala and habenula. Using multiple behavioural assays and both loss-of-function and gain-of-function genetic models, we found that the loss of fam19a5a significantly reduced anxiety-like responses. Interestingly, neuronal overexpression of fam19a5a also reduced anxiety-like responses. Neuronal activity analysis showed altered activity in the septum, pallial amygdala and habenula in fam19a5a-knockout brain without changes in neurotransmitter levels. However, increased neuronal activity was observed in the preoptic area of neuronal fam19a5a-overexpressing zebrafish. Transcriptomic analyses revealed upregulation of anti-inflammatory chemokines and cytokines and downregulation of proinflammatory factors, in both fam19a5a-knockout and neuronal fam19a5a-overexpressing brains. All together, these findings suggest that fam19a5a regulates anxiety-like behaviours in zebrafish by modulating the anti-inflammatory chemokine/cytokine signalling pathways.

The lactation period is considered fundamental in the development of offspring in relation to their metabolism, growth and brain maturation. The aims of this study were to assess the anxiety-like responses and amygdala redox state, in male and female offspring of dams submitted to caloric restriction (CR) or intermittent fasting (IF) diets during lactation. The litters (dam and 8 pups) received the diets: Control—received the lab chow ad libitum (n = 8 litters); CR—received 50% of the chow consumed by the control group (n = 8 litters); IF—received lab chow ad libitum for the first 24 h, followed by a 24-h period without access to food. Assessments of anxiety-like behaviour through the open field, elevated plus maze and light–dark box tests were performed in adolescence. Subsequently, the redox state of the amygdala of the animals was evaluated through FRAP, SOD and TBARS dosages. CR and IF diets during lactation promoted, in male and female offspring, persistent nutritional alterations related to undernutrition. The CR diet led to the development of anxiety-like behaviours in both males and females. Conversely, the IF diet induced a reduction in anxiety-like behaviours only in male offspring. The CR group also showed an increase in SOD enzyme activity in the amygdala, which may be related to the observed behavioural changes. The two models of dietary restriction led to undernutrition in the offspring (male and female), with differing effects on anxiety and redox status.

Chondroitin sulphate proteoglycans (CSPGs) are major contributors to the inhibitory microenvironment that hinders regeneration following spinal cord injury (SCI). Chondroitinase ABC (ChABC) mediated degradation of CSPGs is associated with enhanced regenerative potential following SCI. In this study, the molecular responses of Neurocan, NG2 and Phosphacan CSPGs, as well as cellular markers for pro-inflammatory and neuroprotective microglia, astrocytes, oligodendrocytes and neurons, were investigated following a single subpial injection of ChABC (0.2 U in 10 μL) 14 days after thoracic (Th9) spinal cord compression in adult Wistar rats. qRT-PCR of samples from the lesion epicentre and adjacent cranial and caudal segments, 1 and 7 days after treatment, show that ChABC significantly suppressed Neurocan, NG2 and Phosphacan gene expression and reduced astrocytic (GFAP, S100B) and microglial/macrophage (Iba1, Cx3Cr1) reactivity after 24 h. Although most markers recovered within a week of ChABC delivery, sustained increases were observed for GAP-43, particularly in cranial and caudal segments, suggesting the potential regenerative benefits of ChABC. Correlation analyses revealed region-specific interactions between CSPG expression and glial phenotypes. Phosphacan displayed the strongest positive correlation with pro-inflammatory microglial/macrophage markers (IL-1β, iNOS) and the weakest with neuroprotective markers, suggesting a significant pro-inflammatory role. NG2 was associated with both pro- and anti-inflammatory markers, indicating a more balanced modulatory role, while Neurocan exhibited stronger correlations with neuroprotective markers. These findings highlight the importance of spatial and temporal context for SCI regenerative therapies targeting glial scar responses and support the therapeutic potential of subpial ChABC delivery for modifying the anti-regenerative inhibitory microenvironment following SCI.

A subset of patients with parkinsonian syndromes, particularly older adults, present with early gait dysfunction, postural instability, cognitive–motor dissonance, and limited dopaminergic responsiveness. These features, often labeled as atypical Parkinson's disease (PD), may instead represent a distinct neurovascular endophenotype, vascular parkinsonism (VP), driven by cerebral small-vessel disease (SVD). We introduce the Neurovascular–Locomotor Integration Failure (NLIF) hypothesis, which interprets VP symptoms—especially freezing of gait (FOG)—as manifestations of vascularly mediated network disconnection, rather than late-stage dopaminergic decline. This disruption of fronto-striatal and fronto-parietal integration impairs coordination between cortical motor planning and subcortical execution, producing gait disturbances often refractory to conventional PD therapies. An integrated framework combining the Vasc-PD Stratification Score (VPDS) and the Neurovascular–Degenerative Classification (NDC) delineates three mechanistic phenotypes: Type I—Neuro-Dominant (Idiopathic) PD, Type II—Vascular-Dominant Parkinsonism, and Type III—Mixed Neurovascular PD, capturing the continuum from primary α-synuclein neurodegeneration to cerebrovascular network injury and their intersection. This schema extends traditional nosologies by embedding vascular mechanisms within a unified, mechanism-based diagnostic continuum. Evidence from multimodal neuroimaging, biomarker studies (NfL, homocysteine, VCAM-1, ICAM-1), and pharmacogenomic data (COMT, MAO-B, CYP2D6) supports VP as a potentially modifiable disorder bridging vascular and neurodegenerative processes. Therapeutically, vascular-targeted interventions offer dual neuroprotective and vasculoprotective benefits, while pharmacogenomic stratification may assist in individualized levodopa optimization in mixed phenotypes. By reframing VP and FOG as outcomes of neurovascular integration failure, this framework transitions parkinsonism from a dopamine-centric model to a precision neurovascular paradigm, enabling earlier diagnosis, stratified interventions, and improved patient outcomes.