European Journal of Neuroscience最新文献

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.

While invasive brain stimulation of subcortical structures improves motor symptoms in Parkinson's disease (PD), its effects on speech and language impairments remain inconsistent. Accumulating evidence supports the application of transcranial alternating current stimulation (tACS) to enhance both motor and non-motor functions in the disorder. We conducted a sham-controlled, multisite 4 Hz HD-tACS over the left central and frontal regions in 17 non-demented PD patients. Following stimulation, EEG data were recorded while participants performed action fluency (AF), phonemic fluency (PF), and semantic fluency (SF) tasks. Patients did not show improvement in the number of generated words following stimulation. Relative to sham, the power of prefrontal theta activity significantly increased following actual stimulation for AF; this effect was not observed for PF and SF. Moreover, AF elicited a significant increase in prefrontal theta activity relative to PF and SF following actual stimulation but not sham stimulation. These findings suggest concurrent stimulation of left central and frontal regions selectively modulates oscillatory markers of word retrieval for motion-related words in PD (i.e., action fluency). This modulation does not indicate a general improvement in cognitive control but may suggest that stimulation specifically enhances the neural mechanisms associated with action word retrieval in PD. These results provide novel insights into the application of a non-invasive brain stimulation protocol to enhance neural activity associated with action verb retrieval, which is typically compromised in PD.

Rodents depend heavily on visual information to navigate and orient in complex environments, with the entorhinal–hippocampal circuit playing a central role in generating spatial representations that support this behaviour. It is believed that the medial entorhinal cortex (MEC) mainly captures distal visual cues, while the lateral entorhinal cortex (LEC) apprehends most proximal visual cues, both of which cooperatively construct a coordinate system to encode spatial information. However, it remains unclear how entorhinal–hippocampal circuit jointly generate spatial representation from distal and proximal visual cues and further guide navigational decision-making. To fill these gaps, we developed a model based on the two-dimensional continuous attractor network. In the model, allocentric velocity inputs drive grid-cell attractor dynamics anchored to distal cues in the MEC, while LEC populations encode the positions of proximal cues. Their convergence in hippocampal place cells gives rise to a population code of self-location and object location, enabling a simple vector-subtraction mechanism that supports memory-based, goal-directed navigation. To verify the model, we implemented it on a robotics platform. Through systematic biorobotics experiments, the model successfully replicated key findings from biological studies, including distal cue–controlled rotation of grid–place representations, object-related and proximal cue–coherent responses in the LEC pathway and both coherent and irregular remapping patterns at the hippocampal level. Furthermore, it demonstrated a plausible navigation strategy. Overall, these results offer a mechanistic, population-level explanation of how distal and proximal cues can be integrated to maintain stable allocentric representations and support flexible navigation. The biorobotics implementation further demonstrates the value of embodied approaches for testing computational hypotheses of spatial cognition.