Ying-Shing Chan

Background: Adolescent idiopathic scoliosis (AIS) features structural spinal deformity and impaired postural control, which may be associated with altered vestibular function and multisensory integration. Neuromodulatory approaches such as noisy galvanic vestibular stimulation (nGVS) and high-definition transcranial direct current stimulation (HD-tDCS) have shown promise in enhancing balance in healthy and older populations. However, whether peripheral and cortical vestibular neuromodulation exert distinct or combined effects on postural control in AIS remains unknown. This study aimed to compare the immediate post-stimulation effects of peripheral (nGVS), central (HD-tDCS), and combined (nGVS + HD-tDCS) vestibular modulation on postural control in AIS and explore their neuromuscular and cortical correlates. Methods: Forty adolescents with AIS were randomly assigned to sham, nGVS, HD-tDCS (anodal CP6), or nGVS+tDCS groups. Center of pressure (COP), surface electromyography (EMG) for bilateral gastrocnemius (GM), tibialis anterior (TA), and erector spinae (ES), and functional near-infrared spectroscopy (fNIRS) for bilateral inferior parietal lobule (IPL), superior parietal lobule (SPL), supplementary motor area (SMA), and primary motor cortex (M1) were simultaneously recorded during an eyes-closed foam-standing Romberg task to evaluate behavior, muscular and cortical responses before and after a single-session neuromodulation intervention. Results: Active interventions (nGVS, HD-tDCS, and combined nGVS + HD-tDCS) significantly reduced COP path length and sway area versus sham, with the combined nGVS + HD-tDCS demonstrating the greatest reduction in path length. EMG analysis showed reduced gastrocnemius exertion following nGVS (right side) and combined stimulation (both sides). fNIRS revealed no hemodynamic changes after nGVS, while HD-tDCS increased activation in the right IPL, and enhanced functional connectivity (FC) between the right IPL and right SMA. Combined nGVS + HD-tDCS further amplified right IPL and right SPL activity, and strengthened connectivity within bilateral SMA and between the right IPL and right SMA. Conclusions: nGVS, HD-tDCS, and their combination improve postural control in AIS through distinct neuromodulation mechanisms. Combined stimulation was associated with the largest improvement in COP path length and broader cortical network modulation. Trial registration Registered at Chinese Clinical Trial Registry (ChiCTR2500110347) on July 25, 2025.

Loss of myelinating oligodendrocytes and myelin impairs motor and cognitive functions. Transplantation of autologous oligodendrocyte precursors (OPCs) holds promise for treatment of such diseases, but a protocol to derive human OPCs from a safe, ethical and accessible cell source with the rapidity required to catch the therapeutic window remains to be found. Although we previously generated myelinating glia from rat bone marrow stromal cells (BMSCs), it remains unknown if clinically sourced human BMSCs (hBMSCs) share the same potential. Moreover, whether the multipotency of BMSCs results from diverse progenitors preexisting in the bone marrow or from a single multipotent progenitor population remains unaddressed. Single-cell RNA sequencing data revealed a CD90^hiEGFR⁺PDGFRA⁺ pre-OPC-like subpopulation within hBMSCs. With a small-molecule-based (virus-free and supporting-cell-free) two-step induction protocol designed to expand this pre-OPC population, we generated functional OPCs with high purity in eight days. These derived OPCs showed phenotypic transcriptomes and immunoprofiles. They were also capable of myelinating naked axons when transplanted into myelin-deficient shiverer mice. Results highlight how targeted enrichment and maturation of specific progenitor subpopulations within hBMSCs allows rapid induction of desired cell types. These results place hBMSCs as a robust source of OPCs, unlocking the possibility for cell transplantation therapy for myelin deficiency in the central nervous system.

Navigational decline is a metric distinct from aging-related cognitive degradation, yet the affected circuits and synaptic changes remain elusive. This study identified a long-range excitatory projection from parvalbumin (PV) neurons in the brainstem medial vestibular nucleus (MVN) of mice that monosynaptically innervates the midbrain dorsal tegmental nucleus (DTN). This PV^MVN→DTN projection exhibits high neuronal excitability and synaptic plasticity as electrophysiological traits. In vivo chemogenetic inhibition of the PV^MVN→DTN projection impaired the navigational performance of adult mice. Navigational deficits in aged mice linked to both diminished innervation and synaptic drive of the PV^MVN→DTN pathway were pinpointed as hallmarks of the aging process. Strikingly, targeted activation of this pathway mitigated navigational impairments in older mice. In sum, our results revealed an excitatory PV^MVN→DTN pathway that impacts navigation. Rescue from aging-related navigational decline by activation of a spared projection pathway further highlights the potential for targeted therapies.

GABAergic interneurons are poised with the capacity to shape circuit output via inhibitory gating. How early in the development of medial vestibular nucleus (MVN) are GABAergic neurons recruited for feedforward shaping of outputs to higher centers for spatial navigation? The role of early GABAergic transmission in assembling vestibular circuits for spatial navigation was explored by neonatal perturbation. Immunohistochemistry and confocal imaging were utilized to reveal the expression of parvalbumin (PV)-expressing MVN neurons and their perineuronal nets. Whole-cell patch-clamp recording, coupled with optogenetics, was conducted in vitro to examine the synaptic function of MVN circuitry. Chemogenetic targeting strategy was also employed in vivo to manipulate neuronal activity during navigational tests. We found in rats a neonatal critical period before postnatal day (P) 8 in which competitive antagonization of GABAergic transmission in the MVN retarded maturation of inhibitory neurotransmission, as evidenced by deranged developmental trajectory for excitation/inhibition ratio and an extended period of critical period-like plasticity in GABAergic transmission. Despite increased number of PV-expressing GABAergic interneurons in the MVN, optogenetic-coupled patch-clamp recording indicated null-recruitment of these neurons in tuning outputs along the ascending vestibular pathway. Such perturbation not only offset output dynamics of ascending MVN output neurons, but was further accompanied by impaired vestibular-dependent navigation in adulthood. The same perturbations were however non-consequential when applied after P8. Results highlight neonatal GABAergic transmission as key to establishing feedforward output dynamics to higher brain centers for spatial cognition and navigation.

The in vitro derivation of Schwann cells from human bone marrow stromal cells (hBMSCs) opens avenues for autologous transplantation to achieve remyelination therapy for post-traumatic neural regeneration. Towards this end, we exploited human induced pluripotent stem-cell-derived sensory neurons to direct Schwann-cell-like cells derived from among the hBMSC-neurosphere cells into lineage-committed Schwann cells (hBMSC-dSCs). These cells were seeded into synthetic conduits for bridging critical gaps in a rat model of sciatic nerve injury. With improvement in gait by 12-week post-bridging, evoked signals were also detectable across the bridged nerve. Confocal microscopy revealed axially aligned axons in association with MBP-positive myelin layers across the bridge in contrast to null in non-seeded controls. Myelinating hBMSC-dSCs within the conduit were positive for both MBP and human nucleus marker HuN. We then implanted hBMSC-dSCs into the contused thoracic cord of rats. By 12-week post-implantation, significant improvement in hindlimb motor function was detectable if chondroitinase ABC was co-delivered to the injured site; such cord segments showed axons myelinated by hBMSC-dSCs. Results support translation into a protocol by which lineage-committed hBMSC-dSCs become available for motor function recovery after traumatic injury to both peripheral and central nervous systems.

Dementia is a major burden on global health for which there are no effective treatments. The use of noninvasive visual stimulation to ameliorate cognitive deficits is a novel concept that may be applicable for treating dementia. In this study, we investigated the effects of transcorneal electrical stimulation (TES) on memory enhancement using two mouse models, in aged mice and in the 5XFAD model of Alzheimer's disease. After 3 weeks of TES treatment, mice were subjected to Y‐maze and Morris water maze tests to assess hippocampal‐dependent learning and memory. Immunostaining of the hippocampus of 5XFAD mice was also performed to examine the effects of TES on amyloid plaque pathology. The results showed that TES improved the performance of both aged and 5XFAD mice in memory tests. TES also reduced hippocampal plaque deposition in male, but not female, 5XFAD mice. Moreover, TES significantly reversed the downregulated level of postsynaptic protein 95 in the hippocampus of male 5XFAD mice, suggesting the effects of TES involve a postsynaptic mechanism. Overall, these findings support further investigation of TES as a potential treatment for cognitive dysfunction and mechanistic studies of TES effects in other dementia models.

Transplantation of oligodendrocyte precursors (OPs) is potentially therapeutic for myelin disorders but a safe and accessible cell source remains to be identified. Here we report a two-step protocol for derivation of highly enriched populations of OPs from bone marrow stromal cells of young adult rats (aMSCs). Neural progenitors among the aMSCs were expanded in non-adherent sphere-forming cultures and subsequently directed along the OP lineage with the use of glial-inducing growth factors. Immunocytochemical and flow cytometric analyses of these cells confirmed OP-like expression of Olig2, PDGFRα, NG2, and Sox10. OPs so derived formed compact myelin both in vitro, as in co-culture with purified neurons, and in vivo, following transplantation into the corpus callosum of neonatal shiverer mice. Not only did the density of myelinated axons in the corpus callosum of recipient shiverer mice reach levels comparable to those in age-matched wild-type mice, but the mean lifespan of recipient shiverer mice also far exceeded those of non-recipient shiverer mice. Our results thus promise progress in harnessing the OP-generating potential of aMSCs towards cell therapy for myelin disorders.