Reactivation of Dormant Relay Pathways in Injured Spinal Cord by KCC2 Manipulations.

Many human spinal cord injuries are anatomically incomplete but exhibit complete paralysis. It is unknown why spared axons fail to mediate functional recovery in these cases. To investigate this, we undertook a small-molecule screen in mice with staggered bilateral hemisections in which the lumbar spinal cord is deprived of all direct brain-derived innervation, but dormant relay circuits remain. We discovered that a KCC2 agonist restored stepping ability, which could be mimicked by selective expression of KCC2, or hyperpolarizing DREADDs, in the inhibitory interneurons between and around the staggered spinal lesions. Mechanistically, these treatments transformed this injury-induced dysfunctional spinal circuit to a functional state, facilitating the relay of brain-derived commands toward the lumbar spinal cord. Thus, our results identify spinal inhibitory interneurons as a roadblock limiting the integration of descending inputs into relay circuits after injury and suggest KCC2 agonists as promising treatments for promoting functional recovery after spinal cord injury.

Molecular landscapes of human hippocampal immature neurons across lifespan.

Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity and unique brain functions in rodents1,2 and are dysregulated in multiple human neurological disorders3-5. Little is known about the molecular characteristics of adult human hippocampal imGCs, and even their existence is under debate1,6-8. Here we performed single-nucleus RNA sequencing aided by a validated machine learning-based analytic approach to identify imGCs and quantify their abundance in the human hippocampus at different stages across the lifespan. We identified common molecular hallmarks of human imGCs across the lifespan and observed age-dependent transcriptional dynamics in human imGCs that suggest changes in cellular functionality, niche interactions and disease relevance, that differ from those in mice9. We also found a decreased number of imGCs with altered gene expression in Alzheimer's disease. Finally, we demonstrated the capacity for neurogenesis in the adult human hippocampus with the presence of rare dentate granule cell fate-specific proliferating neural progenitors and with cultured surgical specimens. Together, our findings suggest the presence of a substantial number of imGCs in the adult human hippocampus via low-frequency de novo generation and protracted maturation, and our study reveals their molecular properties across the lifespan and in Alzheimer's disease.

Structurally and mechanically tuned macroporous hydrogels for scalable mesenchymal stem cell-extracellular matrix spheroid production.

Mesenchymal stem cells (MSCs) are essential in regenerative medicine. However, conventional expansion and harvesting methods often fail to maintain the essential extracellular matrix (ECM) components, which are crucial for their functionality and efficacy in therapeutic applications. Here, we introduce a bone marrow-inspired macroporous hydrogel designed for the large-scale production of MSC-ECM spheroids. Through a soft-templating approach leveraging liquid-liquid phase separation, we engineer macroporous hydrogels with customizable features, including pore size, stiffness, bioactive ligand distribution, and enzyme-responsive degradability. These tailored environments are conducive to optimal MSC proliferation and ease of harvesting. We find that soft hydrogels enhance mechanotransduction in MSCs, establishing a standard for hydrogel-based 3D cell culture. Within these hydrogels, MSCs exist as both cohesive spheroids, preserving their innate vitality, and as migrating entities that actively secrete functional ECM proteins. Additionally, we also introduce a gentle, enzymatic harvesting method that breaks down the hydrogels, allowing MSCs and secreted ECM to naturally form MSC-ECM spheroids. These spheroids display heightened stemness and differentiation capacity, mirroring the benefits of a native ECM milieu. Our research underscores the significance of sophisticated materials design in nurturing distinct MSC subpopulations, facilitating the generation of MSC-ECM spheroids with enhanced therapeutic potential.

RSK1 promotes mammalian axon regeneration by inducing the synthesis of regeneration-related proteins.

In contrast to the adult mammalian central nervous system (CNS), the neurons in the peripheral nervous system (PNS) can regenerate their axons. However, the underlying mechanism dictating the regeneration program after PNS injuries remains poorly understood. Combining chemical inhibitor screening with gain- and loss-of-function analyses, we identified p90 ribosomal S6 kinase 1 (RSK1) as a crucial regulator of axon regeneration in dorsal root ganglion (DRG) neurons after sciatic nerve injury (SNI). Mechanistically, RSK1 was found to preferentially regulate the synthesis of regeneration-related proteins using ribosomal profiling. Interestingly, RSK1 expression was up-regulated in injured DRG neurons, but not retinal ganglion cells (RGCs). Additionally, RSK1 overexpression enhanced phosphatase and tensin homolog (PTEN) deletion-induced axon regeneration in RGCs in the adult CNS. Our findings reveal a critical mechanism in inducing protein synthesis that promotes axon regeneration and further suggest RSK1 as a possible therapeutic target for neuronal injury repair.

Congenital myopathies: pathophysiological mechanisms and promising therapies.

Congenital myopathies (CMs) are a kind of non-progressive or slow-progressive muscle diseases caused by genetic mutations, which are currently defined and categorized mainly according to their clinicopathological features. CMs exhibit pleiotropy and genetic heterogeneity. Currently, supportive treatment and pharmacological remission are the mainstay of treatment, with no cure available. Some adeno-associated viruses show promising prospects in the treatment of MTM1 and BIN1-associated myopathies; however, such gene-level therapeutic interventions target only specific mutation types and are not generalizable. Thus, it is particularly crucial to identify the specific causative genes. Here, we outline the pathogenic mechanisms based on the classification of causative genes: excitation-contraction coupling and triadic assembly (RYR1, MTM1, DNM2, BIN1), actin-myosin interaction and production of myofibril forces (NEB, ACTA1, TNNT1, TPM2, TPM3), as well as other biological processes. Furthermore, we provide a comprehensive overview of recent therapeutic advancements and potential treatment modalities of CMs. Despite ongoing research endeavors, targeted strategies and collaboration are imperative to address diagnostic uncertainties and explore potential treatments.

Interfacial Coordinational Bond Triggered Photoreduction Membrane for Continuous Light-Driven Precious Metals Recovery.

Chemical/electric energy-driven processes dominate the traditional precious metal (PM) recovery market. The renewable energy-driven selective PM recycling approach crucial for carbon neutrality is under exploration. Herein, via an interfacial structure engineering approach, coordinational-active pyridine groups are covalently integrated onto the photoactive semiconductor SnS2 surface to construct Py-SnS2. Triggered by the preferred coordinational binding force between PMs and pyridine groups, together with the photoreduction capability of SnS2, Py-SnS2 shows significantly enhanced selective PM-capturing performance toward Au3+, Pd4+, and Pt4+ with recycling capacity up to 1769.84, 1103.72, and 617.61 mg/g for Au3+, Pd4+, and Pt4+, respectively. Further integrating the Py-SnS2 membrane into a homemade light-driven flow cell, 96.3% recovery efficiency was achieved for continuous Au recycling from a computer processing unit (CPU) leachate. This study reported a novel strategy to fabricate coordinational bonds triggered photoreductive membranes for continuous PM recovery, which could be expanded to other photocatalysts for broad environmental applications.

Aldehyde Dehydrogenase 2 (ALDH2) rs671 Polymorphism is a Predictor of Pulmonary Hypertension Due to Left Heart Disease.

AIM: Pulmonary hypertension due to left heart disease (PH-LHD) is commonly seen in patients with heart failure (HF), but there are limited treatment options. Recent studies have shown an association between aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms and pulmonary hypertension (PH). Therefore, this study aimed to investigate the occurrence of ALDH2 rs671 polymorphisms, and the association between ALDH2 and risk of PH-LHD in patients with HF. It also investigated different ALDH2 genotypes and examined their association with cardiac structure and function in HF patients with PH-LHD. METHODS: A total of 178 HF patients were consecutively enrolled in this study: 102 without PH-LHD and 76 with PH-LHD. Clinical data, parameters of echocardiography, and relevant biochemical indexes were recorded in both groups. Differences in data obtained between groups were compared, and the risk of variant ALDH2 polymorphisms with PH-LHD in HF patients was analysed using univariate and multivariate logistic regression. RESULTS: The prevalence of ALDH2 rs671 GA/AA polymorphisms (variant ALDH2) was 24 of 102 patients (23.53%) in the HF without PH-LHD group, and 32 of 76 patients (42.10%) in the HF with PH-LHD group, with a statistically significant difference. Univariate and multivariate logistical regression showed that variant ALDH2 is an independent risk factor for HF combined with PH-LHD. A higher proportion of patients with variant ALDH2 in the HF with PH-LHD group had a tricuspid regurgitation velocity >2.8 m/s, and they had higher values of peak early diastolic velocity of the mitral orifice/peak velocity of the early diastolic wave of the mitral orifice, maximum frequency shift of pulmonary valve flow, and pulmonary artery stiffness. CONCLUSIONS: Variant ALDH2 may be an independent risk factor for HF combined with PH-LHD. Variant ALDH2 may also be involved in pulmonary artery remodelling and is a potential new target for clinical treatment of PH-LHD.

Skin precursor-derived Schwann cells accelerate in vivo prevascularization of tissue-engineered nerves to promote peripheral nerve regeneration.

Prevascularization strategies have become a hot spot in tissue engineering. As one of the potential candidates for seed cells, skin precursor-derived Schwann cells (SKP-SCs) were endowed with a new role to more efficiently construct prevascularized tissue-engineered peripheral nerves. The silk fibroin scaffolds seeded with SKP-SCs were prevascularized through subcutaneously implantation, which was further assembled with the SKP-SC-containing chitosan conduit. SKP-SCs expressed pro-angiogenic factors in vitro and in vivo. SKP-SCs significantly accelerated the satisfied prevascularization in vivo of silk fibroin scaffolds compared with VEGF. Moreover, the NGF expression revealed that pregenerated blood vessels adapted to the nerve regeneration microenvironment through reeducation. The short-term nerve regeneration of SKP-SCs-prevascularization was obviously superior to that of non-prevascularization. At 12 weeks postinjury, both SKP-SCs-prevascularization and VEGF-prevascularization significantly improved nerve regeneration with a comparable degree. Our figures provide a new enlightenment for the optimization of prevascularization strategies and how to further utilize tissue engineering for better repair.

The Value of RBP4 in Assessing Coronary Artery Elasticity in Patients with Coronary Heart Disease and Type 2 Diabetes Mellitus.

Background: Existing research has shown that retinol binding protein (RBP4) has an impairing effect on arterial elasticity and induces insulin resistance, but the clinical value of RBP4 in patients with coronary heart disease (CHD) combined with type 2 diabetes mellitus (T2DM) has not been investigated. This study sought to compare the complexity of coronary artery lesions and coronary artery elasticity between patients with CHD combined with T2DM and those with CHD without T2DM, analyze the risk factors affecting coronary artery elasticity, and investigate the value of RBP4 in assessing coronary artery elasticity in patients with CHD and T2DM. Methods: A total of 130 patients with confirmed CHD were consecutively enrolled, including 38 patients with CHD combined with T2DM and 92 patients with CHD without T2DM. Basic clinical data, laboratory findings, coronary angiography and intravascular ultrasound (IVUS) imaging data, and Gensini scores and coronary artery elasticity parameters were calculated in both groups. Elasticity parameters included: stiffness parameter ( ß ), pressure-strain elastic modulus ( E p ), distensibility coefficient (DC), and compliance coefficient (CC). Multiple linear regression equations were established with elasticity parameters as dependent variables to explore the factors influencing coronary artery elasticity parameters in patients within the two groups. Results: Compared with patients in the CHD without T2DM group, patients in the CHD combined with T2DM group had higher RBP4 levels, Gensini scores, ß and E p values, and lower DC and CC values. Linear regression analysis showed that Gensini score increased with higher ß and E p values and decreased with higher DC and CC values. In all patients in the CHD and CHD combined with T2DM groups, RBP4 was an independent risk factor for ß values after correction for confounders by multiple linear regression analysis, whereas in patients in the CHD without T2DM group, the effect of RBP4 on ß values was not statistically different. Conclusions: RBP4 was an independent risk factor of coronary artery elasticity in CHD patients with T2DM and in overall CHD patients, but it did not affect coronary artery elasticity in CHD patients without T2DM.

Heterogeneity analysis of astrocytes following spinal cord injury at single-cell resolution.

Astrocytes play many important functions in response to spinal cord injury (SCI) in an activated manner, including clearance of necrotic tissue, formation of protective barrier, maintenance of microenvironment balance, interaction with immune cells, and formation of the glial scar. More and more studies have shown that the astrocytes are heterogeneous, such as inflammatory astrocyte 1 (A1) and neuroprotective astrocyte 2 (A2) types. However, the subtypes of astrocyte resulting from SCI have not been clearly defined. In this study, using single-cell RNA sequencing, we constructed the transcriptomic profile of astrocytes from uninjured spinal cord tissue and injured tissue nearby the lesion epicenter at 0.5, 1, 3, 7, 14, 60, and 90 days after mouse hemisection spinal cord surgery. Our analysis uncovered six transcriptionally distinct astrocyte states, including Atp1b2+ , S100a4+ , Gpr84+ , C3+ /G0s2+ , GFAP+ /Tm4sf1+ , and Gss+ /Cryab+ astrocytes. We used these new signatures combined with canonical astrocyte markers to determine the distribution of morphologically and physiologically distinct astrocyte population at injured sites by immunofluorescence staining. Then we identified the dynamic evolution process of each astrocyte subtype following SCI. Finally, we also revealed the evolution of highly expressed genes in these astrocyte subtypes at different phases of SCI. Together, we provided six astrocyte subtypes at single-cell resolution following SCI. These data not only contribute to understand the heterogeneity of astrocytes during SCI but also help to find new astrocyte subtypes as a target for SCI repair.

Single-cell sequencing reveals microglia induced angiogenesis by specific subsets of endothelial cells following spinal cord injury.

Spinal cord injury (SCI) results in dynamic alterations of the microenvironment at the lesion site, which inevitably leads to neuronal degeneration and functional impairment. The destruction of the spinal vascular system leads to a significant deterioration of the milieu, which exacerbates inflammatory response and deprives cells of nutrient support in the lesion. Limited endogenous angiogenesis occurs after SCI, but the cellular events at the lesion site during this process are unclear so far. Here, we performed single-cell RNA sequencing (scRNA-seq) on spinal cord tissues of rats at different time points after SCI. After clustering and cell-type identification, we focused on vascular endothelial cells (ECs), which play a pivotal role in angiogenesis, and drew the cellular and molecular atlas for angiogenesis after SCI. We found that microglia and macrophages promote endogenous angiogenesis by regulating EC subsets through SPP1 and IGF signaling pathways. Our results indicate that immune cells promote angiogenesis by regulating specific subsets of vascular ECs, which provides new clues for exploring SCI intervention.

Wood-Based Self-Supporting Nanoporous Three-Dimensional Electrode for High-Efficiency Battery Deionization.

Developing highly efficient advanced battery deionization (BDI) electrode materials at a low cost is vital for seawater desalination. Herein, a high-efficiency wood-based BDI electrode has been fabricated for seawater desalination, benefiting from the self-supporting three-dimensional (3D) nanoporous structure and rich redox-active sites. The finely tuned rich electrochemical redox active C═O groups on the surface of the wood electrode derived from the facile thermochemical conversion of lignin play a crucial role in the Faradaic cation removal dynamics of BDI. Coupling the 3D wood electrode and a polyaniline-modified wood electrode as the cathode and anode, an all-wood-electrode-based deionization battery has been successfully assembled with a state-of-the-art ion removal capacity of up to 164 mg g-1 in seawater. Our work reported an example of utilizing wood as the BDI electrode via fine-tuning the redox-active sites, demonstrating a novel resource utilization pathway of converting cheap biomass into BDI electrodes for highly efficient seawater desalination.

Elevated Serum Retinol Binding Protein 4 is Associated with the Risk of Diabetic Cardiomyopathy.

Background: Retinol binding protein 4 (RBP4), a biomarker for insulin resistance in type 2 diabetes (DM), is increased in heart failure. This case-control study aims to determine the association between serum RBP4 levels and diabetic cardiomyopathy (DCM). Methods: Demographic and clinical data were obtained from 245 DM patients and 102 non-diabetic controls. RBP4 levels were measured using ELISA. The association between RBP4 and DCM was evaluated using multivariate logistic regression and restricted cubic splines (RCS) in DM patients. Results: We showed that serum RBP4 levels were higher in DCM patients than in DM patients without DCM or the controls. Multivariate analysis adjusted by age, gender, body mass index, diabetes duration, left ventricular ejection fraction, insulin treatment, triglycerides, low-density lipoprotein cholesterol, estimated glomerular filtration rate, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy and log N-terminal proBNP showed a significant association between RBP4 and DCM (highest vs. lowest tertile OR 16.87, 95% CI: 6.58, 43.23, p < 0.001). RCS displayed a positive linear correlation between RBP4 levels and the risk of DCM in diabetes (p = 0.004). Adding RBP4 to a basic risk model for DCM improved the reclassification (Net reclassification index: 87.86%, 95% CI: 64.4%, 111.32%, p < 0.001). Conclusions: The positive association between serum RBP4 and DCM suggested the role of RBP4 as a potential diagnostic biomarker for distinguishing DCM in patients with DM.

CircTUBGCP3 Contributes to the Malignant Progression of Rectal Cancer.

BACKGROUND: Circular RNA (circRNA) tubulin gamma complex associated protein 3 (circTUBGCP3) has been reported to play an oncogenic role in colorectal cancer and osteosarcoma. AIMS: We further assessed the role and working mechanism of circTUBGCP3 in rectal cancer progression. METHODS: Colony formation assay and transwell assays were performed to analyze cell colony formation ability and motility. Flow cytometry was utilized to assess cell cycle progression and cell apoptosis. The production of lactate and the consumption of glucose were evaluated by fluorescence-based glucose/lactate assay kit to analyze cell glycolysis. The intermolecular interaction was verified by dual-luciferase reporter assay. In vivo experiments were carried out to analyze the role of circTUBGCP3 in tumor growth using xenograft tumor model. RESULTS: CircTUBGCP3 was significantly up-regulated in rectal cancer tissues and cell lines. CircTUBGCP3 interference inhibited the colony formation ability, migration, invasion, cell cycle progression, and glycolysis and promoted the apoptosis in rectal cancer cells. CircTUBGCP3 negative regulated microRNA-375 (miR-375) expression through interacting with it and circTUBGCP3 silencing-mediated effects in rectal cancer cells were largely based on the up-regulation of miR-375. Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) was a target of miR-375, and ROCK1 was regulated by circTUBGCP3/miR-375 axis in rectal cancer cells. MiR-375 overexpression suppressed the malignant behaviors of rectal cancer cells partly through down-regulating ROCK1. CircTUBGCP3 interference restrained rectal cancer progression in vivo. CONCLUSION: CircTUBGCP3 acted as an oncogene to promote the malignant phenotypes of rectal cancer cells by modulating miR-375/ROCK1 axis.

CircORC2 is involved in the pathogenesis of slow transit constipation via modulating the signalling of miR-19a and neurotensin/motilin.

In this study, we aimed to investigate the role of circORC2 in modulating miR-19a and its downstream signalling during the pathogenesis of STC. In this study, three groups of patients, that is healthy control (HC) group, normal transit constipation (NTC) group (N = 42) and slow transit constipation (STC) group, were, respectively, recruited. RT-PCR and Western blot analysis were exploited to investigate the changes in the expression levels of miR-19a and circORC2 in these patients, so as to establish a circORC2/miR-19a signalling pathway. The basic information of the patients showed no significant differences among different patient groups. Compared with the HC group, concentrations of neurotensin (NST) and motilin (MLN) were both significantly reduced in the NTC and STC groups, especially in the STC group. Also, miR-19a level was highest, whereas circORC2 level was lowest in the STC group. Furthermore, circORC2 was validated to sponge the expression of miR-19a, and the transfection of circORC2 reduced the expression of miR-19a. Meanwhile, MLN and NST mRNAs were both targeted by miR-19a, and the transfection of circORC2 dramatically up-regulated the expression of MLN and NST. On the contrary, the transfection of circORC2 siRNA into SMCs and VSMCs exhibited the opposite effect of circORC2. Collectively, the results of this study established a regulatory relationship among circORC2, miR-19a and neurotensin/motilin, which indicated that the overexpression of circORC2 could up-regulate the levels of neurotensin and motilin, thus exerting a beneficial effect during the treatment of STC.

The long noncoding RNA Arrl1 inhibits neurite outgrowth by functioning as a competing endogenous RNA during neuronal regeneration in rats.

The intrinsic regeneration ability of neurons is a pivotal factor in the repair of peripheral nerve injury. Therefore, identifying the key modulators of nerve regeneration may help improve axon regeneration and functional recovery after injury. Unlike for classical transcription factors and regeneration-associated genes, the function of long noncoding RNAs (lncRNAs) in the regulation of neuronal regeneration remains mostly unknown. In this study, we used RNA-Seq-based transcriptome profiling to analyze the expression patterns of lncRNAs and mRNAs in rat dorsal root ganglion (DRG) following sciatic nerve injury. Analyses using the lncRNA-mRNA co-expression network, gene ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway databases indicated that the lncRNA Arrl1 decreases neurite outgrowth after neuronal injury. shRNA-mediated Arrl1 silencing increased axon regeneration both in vitro and in vivo and improved functional recovery of the sciatic nerve. Moreover, inhibiting an identified target gene of Arrl1, cyclin-dependent kinase inhibitor 2B (Cdkn2b), markedly promoted neurite outgrowth of DRG neurons. We also found that Arrl1 acts as a competing endogenous RNA that sponges a Cdkn2b repressor, microRNA-761 (miR-761), and thereby up-regulates Cdkn2b expression during neuron regeneration. We conclude that the lncRNA Arrl1 affects the intrinsic regeneration of DRG neurons by derepressing Cdkn2b expression. Our findings indicate a role for an lncRNA-microRNA-kinase pathway in the regulation of axon regeneration and functional recovery following peripheral nerve injury in rats.

Cell populations in neonatal rat peripheral nerves identified by single-cell transcriptomics.

Peripheral nerves connect central nerves with target tissues and organs and execute vital signal transduction functions. Although sub-types of neurons have been defined, the heterogeneity of cell populations in peripheral nerves, especially Schwann cells, has not been well demonstrated. Here, we collected sciatic nerves (SN) and dorsal root ganglia (DRG) from neonatal (1-day old) rats and classified cell populations by high-coverage single-cell sequencing. A total of 10 types of cells, including endothelial cells, erythrocytes, fibroblasts, monocytic cells, neurons, neutrophils, pericytes, satellite cells, Schwann cells, and vascular smooth muscle cells, were identified by transcriptome-based cell typing. The comparisons of cells in neonatal rat SN and DRG revealed distinct atlas in different tissue localizations. Investigations of ligand-receptor interactions showed that there existed direct cell-cell communications between endothelial cells and fibroblasts in SN and among endothelial cells, fibroblasts, and vascular smooth muscle cells in DRG. Schwann cells in neonatal rats were further sub-grouped to four sub-types, including LOC100134871 and Hbb expressing Schwann cell sub-type 1, Cldn19 and Emid1 expressing Schwann cell sub-type 2, Timp3 and Col5a3 expressing Schwann cell sub-type 3, and Cenpf and Mki67 expressing Schwann cell sub-type 4. These Schwann cell sub-types exhibited distinct genetic features and functional enrichments. Collectively, our results illustrated the diversity and cellular complexity of peripheral nerves at the neonatal stage and revealed the heterogeneity of Schwann cells in the peripheral nervous system.

Loc680254 regulates Schwann cell proliferation through Psrc1 and Ska1 as a microRNA sponge following sciatic nerve injury.

Peripheral nerve injury triggers sequential phenotype alterations in Schwann cells, which are critical for axonal regeneration. Long noncoding RNAs (lncRNAs) are long transcripts without obvious coding potential. It has been reported that lncRNAs participate in diverse biological processes and diseases. However, the role of lncRNA in Schwann cells and peripheral nerve regeneration is unclear. Here, we identified an lncRNA, loc680254, which is upregulated in rat sciatic nerve after peripheral nerve injury. The loc680254 knockdown inhibits Schwann cell proliferation, enhances apoptosis, and hinders cell cycle, while loc680254 overexpression has the opposite effect. Mechanically, we found that loc680254 might act as a microRNA sponge to regulate the expression of mitosis-related gene, spindle and kinetochore associated complex subunit 1 (Ska1) and proline/serine-rich coiled-coil 1 (Psrc1). Silencing of Psrc1 or Ska1 attenuates the effect of loc680254 overexpression on Schwann cell proliferation. Finally, we repaired the rat sciatic nerve gap with chitosan scaffolds loaded with loc680254-overexpressing Schwann cells and evaluated axon regeneration and functional recovery. Our results indicated that loc680254 is a new potential modulator for Schwann cell proliferation, which could be targeted to develop novel therapeutic strategies for peripheral nerve repair.

Tau modulates Schwann cell proliferation, migration and differentiation following peripheral nerve injury.

Tau protein (encoded by the gene microtubule-associated protein tau, Mapt) is essential for the assembly and stability of microtubule and the functional maintenance of the nervous system. Tau is highly abundant in neurons and is detectable in astrocytes and oligodendrocytes. However, whether tau is present in Schwann cells, the unique glial cells in the peripheral nervous system, is unclear. Here, we investigated the presence of tau and its coding mRNA, Mapt, in cultured Schwann cells and find that tau is present in these cells. Gene silencing of Mapt promoted Schwann cell proliferation and inhibited Schwann cell migration and differentiation. In vivo application of Mapt siRNA suppressed the migration of Schwann cells after sciatic nerve injury. Consistent with this, Mapt-knockout mice showed elevated proliferation and reduced migration of Schwann cells. Rats injected with Mapt siRNA and Mapt-knockout mice also exhibited impaired myelin and lipid debris clearance. The expression and distribution of the cytoskeleton proteins α-tubulin and F-actin were also disrupted in these animals. These findings demonstrate the existence and biological effects of tau in Schwann cells, and expand our understanding of the function of tau in the nervous system.