Biology subjects

Chandran, S.

Publications and source records attributed to Chandran, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Tetrahydrobiopterin restores oligodendrocyte maturation after hypoxic white matter injury by reprogramming translational output

Complex congenital heart defects (CHDs) are frequently associated with chronic cerebral hypoxemia, leading to impaired white matter maturation. One proposed mechanism involves hypoxia-induced disruption of the nitric oxide synthase cofactor tetrahydrobiopterin (BH4), resulting in oxidative stress and impaired oligodendrocyte (OL) development. While our previous studies found BH4 supplementation improves hypoxia-induced white matter dysmaturation, the molecular mechanisms remain incompletely understood. Because OL maturation requires coordinated translational control, we hypothesized that BH4 promotes white matter maturation by restoring translation programs disrupted by hypoxia.Translating Ribosome Affinity Purification sequencing (TRAP-seq) was performed on OL lineage cells isolated from transgenic ribosomal reporter mice exposed to chronic hypoxia with or without daily BH4 treatment. Differential translation, weighted gene co-expression network analysis, pathway enrichment, RNAscope, and immunohistochemistry identified translational programs associated with hypoxia and BH4-mediated rescue. Developmental hypoxia extensively altered the OL translatome, suppressing transcripts associated with OL maturation while enriching pathways related to translational regulation and cellular stress. Network analyses identified BH4-responsive gene modules enriched for OL maturation, protein metabolism, and translation-related processes. BH4 partially reversed hypoxia-induced translational changes, restored OL maturation gene expression, and normalized nuclear localization of the lineage regulator OLIG1, consistent with recovery of maturation-associated regulatory programs. Developmental hypoxia disrupts OL maturation through coordinated alterations in ribosome-associated gene expression and post-transcriptional regulatory pathways. BH4 promotes recovery of OL maturation programs, including restoration of translation-related networks and OLIG1 nuclear localization, providing mechanistic insight into BH4-supported white matter maturation under chronic hypoxic conditions.

neuroscience↗

bioRxiv2026

Fatty acid binding protein-8 (FABP8/PMP2) reveals molecular heterogeneity of myelin sheaths in the human CNS

Myelin is classically viewed as a uniform axon-insulating membrane, yet its molecular composition may differ between species and even within one species. Fatty acid binding protein-8 (FABP8/PMP2) was previously identified in CNS myelin of humans but not mice. Here we show that FABP8/PMP2 is a defining feature of CNS myelin in humans and old-world-monkeys, but absent from CNS myelin in other mammals, indicating evolutionary neofunctionalization of this lipid-binding protein in the primate lineage. In the human CNS, FABP8/PMP2 marks a subset of myelin sheaths that preferentially ensheath large-diameter axons, revealing sheath-to-sheath molecular heterogeneity correlated with axonal geometry. Chromatin is accessible at the PMP2/Pmp2 gene locus in oligodendrocytes of humans but not mice. Human oligodendrocytes intrinsically express FABP8/PMP2 when transplanted into mouse brains, demonstrating species-specific competence independent of environmental cues. Humanized transgenic mice expressing FABP8/PMP2 in oligodendrocytes form morphologically normal but developmentally transiently thicker myelin sheaths, and show elevated cholesterol content in purified myelin. Because FABP8/PMP2 binds cholesterol, we propose that its emergence in primate CNS myelin contributes to the cholesterol enrichment of human myelin. Thus, CNS myelin protein composition is evolvable and modular, with relevance for myelin lipids and morphology, and previously unrecognized complexity in neuron-glia co-adaptation. Main points- Fatty acid binding protein 8 (FABP8/PMP2) is present in CNS myelin of humans and old-world monkeys - PMP2 defines sheath-to-sheath heterogeneity in the human CNS - PMP2-immunopositive myelin ensheaths large-diameter axons - Human oligodendrocytes intrinsically express PMP2 upon transplantation into mice - Humanized PMP2-transgenic mice show thicker myelin and altered myelin lipid composition

neuroscience↗

bioRxiv2026

Comparison of Human Intestinal Enteroids and Zebrafish Larvae models for replication of Human Norovirus

Human intestinal enteroids (HIE) and zebrafish larvae (ZF) models support the replication of certain strains of human norovirus (HuNoV), the leading cause of viral gastroenteritis worldwide. The replication of 17 HuNoV (9 genotypes) positive stool specimens from patients ranging from 5 months to 83 years old was evaluated in both HIE and ZF models. The yolk of 3-day post-fertilization ZF larvae were microinjected with 3 nL 10% clarified stool suspension. Each day post-infection (dpi), 10 larvae were pooled as one sample, and two specimens were collected daily until 5 dpi. Viral RNA was extracted from harvested larvae and quantified using reverse transcription (RT) droplet digital PCR. For the HIE model, J4FUT2 K1 enteroid monolayers were inoculated with 100-fold dilution of each stool specimen. Viral RNA levels were quantified at 1 and 72 h post-infection using RT real-time PCR. All genogroup (G) I specimens (n=5) replicated in both models showing a 1 to 2.5 log increase in HuNoV RNA. Of the 12 GII specimens tested, 8 replicated in the ZF model and 7 replicated in the HIE model. Specimens that failed to replicate in each model were not the same, although most of them were GII.4 Sydney [P16]. One additional strain, GII.17[P17], replicated only in the ZF model. Among the GII strains, viral RNA increase ranged from 1.6 to 3.3 log in the ZF and 0.4 to 3.68 log in the HIE model. These data highlight variability in HuNoV replication efficiency across models, potentially indicating the influence of model-specific factors on replication. ImportanceHuman intestinal enteroid and ZF models have been independently shown to support replication of different strains of HuNoV, the leading cause of viral gastroenteritis worldwide. However, whether the same HuNoV positive stool specimens replicate similarly in both systems has not been examined. In this study, stool specimens positive for a range of HuNoV genotypes were tested in both models. While specimens from the GI genogroup consistently replicated in both systems, specimens from the GII genogroup showed variable replication, with some replicating in only one model and a couple of specimens not replicating in either model. These findings demonstrate that model specific biological factors influence HuNoV replication and highlight the significance of using complementary model systems to better understand HuNoV pathogenesis.

microbiology↗

bioRxiv2025

Mislocalisation of TDP-43 to the cytoplasm of either neurons or oligodendrocytes causes axonopathy and dysmyelination

Neurons with large, myelinated axons are vulnerable to degeneration across the amyotrophic lateral sclerosis (ALS) frontotemporal dementia (FTD) disease spectrum. The defining molecular pathology of this spectrum is mislocalisation of the RNA binding protein TDP-43 from the nucleus to the cytoplasm. Even though cytoplasmic TDP-43 is prevalent in neurons and oligodendrocytes, how these molecular pathologies contribute to neurodegeneration remains unclear. Here we developed humanised zebrafish in which we restricted TDP-43 to the cytoplasm of either neurons or oligodendrocytes. Cytoplasmic TDP-43 restricted to neurons led to a severe axonopathy, with extreme distal axonal swelling and reduced myelination. Axonopathy was mirrored by cell type specific loss of TDP-43 function from neurons, pointing to loss of function, rather than a toxic gain of function of mislocalised TDP-43, as driving this phenotype. Preventing oligodendrocyte differentiation and myelination when TDP-43 was mislocalised in neurons exacerbated axonopathy, indicating that oligodendrocytes limit neurodegeneration. Indeed, when TDP-43 was mislocalised to the cytoplasm of oligodendrocytes this also led to axonopathy and reduced myelination, pointing to complex contributions of neurons and oligodendrocytes to neurodegeneration.

neuroscience↗

bioRxiv2025

Absence of short-term axon initial segment plasticity in human, mouse, and rat cortical circuits

Maintaining neuronal output with respect to input in the physiological range relies on the ability of neurons to update their responsiveness to inputs dependent on changing activity levels. Termed homeostatic plasticity, the mechanisms that neurons employ to control their responsiveness are varied, and proposed to include structural changes to a key neuronal structure - the axon initial segment (AIS). As the site of action potential initiation, the AIS has been postulated to rapidly change its length in response to increased or decreased cellular and circuit activity. To date, AIS structural plasticity has only been tested in tissue cultures and rodent models. In our current study, we assess the ability of neurons to alter their AIS length over a variety of timescales in ex vivo rodent and human brain slices, human neurons derived from induced pluripotent stem cells, and in mice dark-reared during early life; using a combination of electrophysiology and immunohistochemistry. We find no evidence for changes to AIS length following depolarisation for up to 3 hours, despite positive controls confirming modulated activity. However, we do find that neuronal physiological properties are altered by changes in activity - but these are largely independent of action potential initiation associated with the AIS. In summary, we find no evidence supporting a role for AIS structural plasticity in mouse, rat, or human cortical neurons.

neuroscience↗

bioRxiv2025

Electrical stimulation elicits space- and parameter-dependent spiking responses in human cortical organoids

Electrical stimulation (ES) is used to treat neuropsychiatric disorders and investigate brain dynamics, yet its effects on human cortical microcircuits remain poorly understood. Cortical organoids provide a unique platform to investigate these mechanisms in isolation from subcortical and long-range cortical inputs. Here we illustrate how cortical organoids respond to ES, identifying the response profiles of isolated cortical circuits while detailing a roadmap of how ES parameters affect the organoid spiking activity. We employed a high-density multielectrode array to record neuronal activity from cortical organoids (n=417 units in N=7 organoids) during ES, systematically varying stimulation frequency, intensity, pulse width, and charge density. By analyzing single unit spiking activity, we found that ES elicits excitatory, inhibitory, and mixed responses in 39%, 12%, and 17% of the units, respectively. On average, this response lasted 100 ms and became stable within 26 trials. The magnitude of both excitatory and inhibitory responses was maximal near the stimulation site and decayed with distance. The response magnitude was inversely correlated with pulse intensity and duration, but not with stimulation frequency and charge density. These findings demonstrate that local cortical circuits are sufficient to initiate the early excitatory phase of the canonical ES response, whose magnitude depends on ES parameters, and can sustain the excitatory phase for over 100 ms. The reduced late inhibitory phase, together with the absence of late excitatory components observed 200 ms after ES in intact adult brains in-vivo, suggests that these phases may depend on neuronal maturation or inter-area connections. Our work thus establishes cortical organoids as a framework for studying the local contributions to ES-induced activity in a developmental model of the human cortex.

neuroscience↗

bioRxiv2025

Astrocytes control motor neuronal mitochondrial axonal transport deficits in C9ORF72 ALS.

Disrupted axonal transport and astrocyte dysfunction are implicated in amyotrophic lateral sclerosis (ALS). Here, we show these are intrinsically linked: human induced pluripotent stem cell-derived astrocytes carrying the C9ORF72 mutation disrupt axonal transport and mitochondrial function in motor neurons (MNs). Conversely, either isogenic gene-corrected astrocytes or selectively boosting C9ORF72-astrocyte mitochondrial bioenergetics rescue axonal transport deficits in C9ORF72-MNs. Thus, astrocytes have a dominant effect on axonal mitochondrial transport in the context of ALS.

neuroscience↗

bioRxiv2024

Heterogeneity in chromatin structure drives core regulatory pathways in B-cell Acute Lymphoblastic Leukemia

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy. Based on gene expression profiling, B-ALL can be classified into distinct transcriptional subtypes with differing disease outcomes. Many of these transcriptional subtypes are defined by mutations in transcription factors and chromatin-modifying enzymes, but how such diverse mutations lead to distinct transcriptional subtypes remains unclear. To illuminate the chromatin regulatory landscape in B-ALL, we analyzed 3D genome organization, open chromatin, and gene expression in 53 primary patient samples. At the level of 3D genome organization, we identified chromatin interactions that vary across transcriptional subtypes. These sites of variable 3D chromatin interactions correlate with local gene expression changes and are enriched for core drivers of B-ALL observed in genome-wide CRISPR knock-out screens. Sites of variable 3D genome interactions are frequently shared across multiple transcriptional subtypes and are enriched for open chromatin sites found in normal B-cell development but repressed in mature B-cells. Within an individual patient sample, the chromatin landscape can resemble progenitor chromatin states at some loci and mature B-cell chromatin at others, suggesting that the chromatin in B-ALL patient tumor cells is in a partially arrested immature state. By analyzing transcriptomic data from large cohorts of B-ALL patients, we identify gene expression programs that are shared across transcriptional subtypes, associated with B-cell developmental stages, and predictive of patient survival. In combination, these results show that the 3D genome organization of B-ALL reflects B-cell developmental stages and helps illustrate how B-cell developmental arrest interacts with transcriptional subtypes to drive B-ALL.

cancer biology↗

bioRxiv2024

The Fragile X Messenger Ribonucleoprotein 1 regulates the morphology and maturation of human and rat oligodendrocytes

The Fragile X Messenger Ribonucleoprotein (FMRP) is an RNA binding protein that regulates the translation of multiple mRNAs and is expressed by neurons and glia in the mammalian brain. Loss of FMRP leads to Fragile X Syndrome (FXS), a common inherited form of intellectual disability and autism. While most research has been focusing on the neuronal contribution to FXS pathophysiology, the role of glia, particularly oligodendro-cytes, is largely unknown. FXS individuals are characterised by white matter changes which imply impairments in oligodendrocyte differentiation and myelination. We hypothesized that FMRP regulates oligodendrocyte maturation and myelination during postnatal development. Using a combination of human pluripotent stem cell - derived oligodendrocytes and an Fmr1 knockout rat model, we studied the role of FMRP on mammalian oligodendrocyte development. We found that the loss of FMRP leads to shared defects in oligodendrocyte morphology in both rat and human systems in vitro which persist in the presence of FMRP expressing axons in chimeric engraftment models. Our findings point to species-conserved, cell-autonomous defects during oligodendrocyte maturation in FXS.

neuroscience↗

bioRxiv2024

Human induced pluripotent stem cell-derived microglia contribute to thepathophysiology of Fragile X syndrome via increased RAC1 signaling

Fragile X syndrome (FXS) is one of the most common monogenic causes of neurodevelopmental disorders characterized by intellectual disability, autism and epilepsy. Emerging evidence suggests a role for immune dysfunction in autism. Using induced pluripotent stem cell (iPSC)-derived microglial cells from FXS patients (mFXS-MG) and FMR1-deficient microglia from FMR1-knock out human embryonic stem cells (FMR1 KO-MG), we show that loss-of-function of Fragile X Messenger Ribonucleoprotein (FMRP) leads to cell autonomous phagocytic deficits and a proinflammatory state in microglia when compared to gene-corrected controls. Moreover, increased RAC1 signaling in mFXS-MG and FMR1 KO-MG results in increased actin polymerization and enhanced activation of NF-{kappa}B signaling. Exposure of control iPSC-derived cortical neuron cultures to conditioned medium from proinflammatory mFXS-MG results in hyperexcitability. Importantly, pharmacological inhibition of RAC1 signaling in mFXS-MG attenuates their proinflammatory profile and corrects the neuronal hyperexcitability caused by the conditioned medium. Our results suggest that microglia impair neuronal function in FXS, which can be prevented by targeting of RAC1 signaling. Significance statementFXS is one of the most common monogenic causes of neurodevelopmental disorders characterized by intellectual disability, autism, epilepsy and has been associated with immune dysfunction. We therefore generated brain macrophages (microglia) from patient-derived induced pluripotent stem cells (mFXS-MG) and an embryonic stem cell line deficient in the Fragile X messenger ribonucleoprotein 1 (FMR1 KO-MG). We find enhanced activation of RAC1 signaling resulting in phagocytic deficits and immune activation of mFXS-MG and FMR1 KO-MG. Exposure of control iPSC-derived cortical neurons to conditioned medium from proinflammatory mFXS-MG results in neuronal hyperexcitability, which can be prevented by pharmacological RAC1 inhibition in mFXS-MG. We conclude that RAC1 signaling in microglia could be a potential therapeutic target in FXS.

neuroscience↗

bioRxiv2023

Robust acidic pH and digestive enzyme stability of anti-SarsCov2 IgY antibodies: Implications for treatment of viral transmission thru gastrointestinal, ocular, nasal and skin tissues

There are many paths for the transmission of SarsCov2 virus. The main routes are nasal and oral and the droplets carrying the virus can also be transmitted thru ocular and skin tissues. The gastrointestinal (small intestine), nasal, ocular and skin tissues all present an acidic pH milieu and therefore any treatment with antibodies thru these routes has to have the antibodies remain active at acid pH as well as be resistant to typical protease digestion. To this end we profiled our anti-SarasCov2 receptor binding domain IgY antibodies for retention of activity at acidic and basic pHs and trypsin digestion. We find that the IgY are strongly resistant to denaturation at acid pH as well as not digested by trypsin. Our data strongly support the use of these IgY in treatment of viral transmission thru the GI, nasal, ocular and skin all tissues where the pH is acidic. We also provide an enabling platform to rapidly asses the suitability of any antibody or protein therapeutic for use at acidic pH.

pharmacology and toxicology↗

bioRxiv2023

Targeted neutralizing IgY antibodies against SGLT1 glucose transporter reduce glucose uptake and improve glycemic profile in vivo

Despite the use of several drugs available to treat type 2 diabetes, many patients are unable to reach their target fasting plasma glucose and HbA1c levels. SGLT1 is the major intestinal transport transmembrane protein which functions in uptake of dietary glucose. If we antagonise the binding of dietary glucose to this transport protein, it is expected that blood glucose lowering will follow. We designed specific inhibitory avian antibodies (IgY) against the extracellular glucose binding domain of SGLT1 and tested their potential in glucose lowering. We demonstrate here the antibodies block uptake of glucose and improve the glycemic profile in vivo and represent a novel approach to inhibiting dietary glucose absorption as treatment for diabetes.

pharmacology and toxicology↗

bioRxiv2023

An Anti-diabetic Nutraceutical enhances muscle cell glucose uptake of cardiometabolic drugs

Type 2 diabetes is currently treated by multiple drugs that are often combined to achieve maximum blood glucose lowering in patients. Yet more than 50% of patients are unable to attain target glucose levels. There is clear need for agents which can be added to current drugs to help patients achieve their target blood glucose levels safely. To this end we tested an anti-diabetic nutraceutical for its ability to enhance glucose uptake in muscle cells in combination with currently used cardiometabolic drugs. We show here that the nutraceutical is able to effectively improve glucose uptake of multiple drugs suggesting that it may help in enhancement of glucose lowering by the drugs in patients and achieve optimal glucose levels.

pharmacology and toxicology↗

bioRxiv2023

Human Bone Marrow Plasma Cell Atlas: Maturation and Survival Pathways Unraveled by Single Cell Analyses

Human bone marrow (BM) plasma cells are heterogeneous, ranging from newly arrived antibody-secreting cells (ASC) to long-lived plasma cells (LLPC). We provide single cell transcriptional resolution of 17,347 BM ASC from 5 healthy adults. Fifteen clusters were identified ranging from newly minted ASC (cluster 1) expressing MKI67 and high MHC Class II that progressed to late clusters 5-8 through intermediate clusters 2-4. Additional clusters included early and late IgM-predominant ASC of likely extra-follicular origin; IFN-responsive; and high mitochondrial activity ASC. Late ASCs were distinguished by differences in G2M checkpoints, MTOR signaling, distinct metabolic pathways, CD38 expression, and utilization of TNF-receptor superfamily members. They mature through two distinct paths differentiated by the degree of TNF signaling through NFKB. This study provides the first single cell resolution atlas and molecular roadmap of LLPC maturation, thereby providing insight into differentiation trajectories and molecular regulation of these essential processes in the human BM microniche. This information enables investigation of the origin of protective and pathogenic antibodies in multiple diseases and development of new strategies targeted to the enhancement or depletion of the corresponding ASC. One Sentence Summary: The single cell transcriptomic atlas of human bone marrow plasma cell heterogeneity shows maturation of class-switched early and late subsets, specific IgM and Interferon-driven clusters, and unique heterogeneity of the late subsets which encompass the long-lived plasma cells.

immunology↗

bioRxiv2022

Evolutionary divergence of basal and activity-dependent exon splicing in cortical neurons

Alternative splicing of mRNA exons in mammalian neurons increases diversity of the proteome and is regulatable by signaling pathways. However, the degree of conservation of basal and signal-dependent exon usage between human neurons and those from experimental models such as mice is incompletely understood. We previously showed that cortical neuronal activity-dependent gene transcription exhibits human/mouse differences, driven by evolutionary divergence of cis-acting promoter elements (Qiu et al. 2016). Since alternative exon usage influences brain development and cognition, is controlled by neuronal activity, and is disturbed in brain disorders, we investigated human/mouse differences in exon usage in cortical neurons. Comparing orthologous exons, basal exon inclusion levels showed human-mouse conservation, but also significant differences determined by cis-acting sequences: human-mouse conservation and divergence in exon usage was recapitulated in neurons from Tc1 mice carrying human chromosome-21 (hCh21). Activity-dependent changes in exon usage also exhibited significant conservation: gene structure was more likely to be conserved in activity-regulated exons, and exons regulated in both human and mouse neurons were enriched in RBFOX and SAM68 targets, and genes were centred on cytoskeletal organisation, mRNA transcription/processing, and synaptic signaling. However, divergence was also evident, and human-specific activity-dependent exon usage was dominated by genes involved in lipid biosynthesis, signaling and trafficking. Notably, the pattern of activity-dependent usage of hCh21 exons in human neurons was not recapitulated in mouse Tc1 neurons. Thus, unlike species-specific differences in activity-dependent gene transcription, cis-acting DNA sequence divergence is insufficient to explain inter-species differences in activity-regulated exon usage. Trans-acting factors involved in activity-responsive splicing have likely also diverged.

neuroscience↗

bioRxiv2022

Suppression of insulin stimulated muscle glucose uptake by non-caloric sweetener sucralose and its reversal by an antidiabetic nutraceutical supplement

Non caloric sweeteners (NCS) have been used for decades now as sugar substitutes in foods and beverages. The market for such products has grown immensely over time. There are human studies which report their negative effects on glucose metabolism with various results of disturbances in glucose metabolism, weight gain etc. No studies to the best of our knowledge have directly addressed the impact of the NCS on muscle glucose uptake. Muscle tissue can account for over 70 percent of whole-body glucose uptake. Therefore, we examined directly the effect of NCS on muscle cell glucose uptake. We find that aspartame moderately increased insulin stimulated glucose uptake by muscle cells in vitro. But sucralose, saccharin and stevia suppressed insulin stimulated glucose uptake. Sucralose is one of the most often used sweetener in foods and beverages globally it is important to understand its effects on glucose metabolism. Therefore, we explored the mechanism of its inhibition of glucose uptake by using an anti-diabetic nutraceutical which is known to target insulin mediated glucose uptake and metabolism pathways. We show here that the nutraceutical is able to relieve the suppression by sucrose in muscle uptake by a novel mechanism of action. We propose that such nutraceuticals may be useful to combine with sucralose containing products to offset negative effects of the NCS on glucose metabolism.

pharmacology and toxicology↗

bioRxiv2022

Investigation into the Phenological Patterns of Trees in Socorro Plateau, Goa

Phenology is defined as the observation of biological events or life cycle phases that occur due to changes in climate and season. Primarily, phenology of all organisms is influenced by temperature fluctuations and quick climate changes which in turn regulate a variety of environmental factors. When discussing about the effects of climate change on ecosystems, phenology is especially important as many animals depend on the phenology of plants for their survival. Analysing the phenological patterns of a particular area can provide us with critical points on how ecosystems are affected by climate change. In this study, we have analysed the patterns of phenology for several trees and tried to identify any idiosyncrasies which may arise as a result of climate change and other similar factors. A total of 75 individuals belonging to 15 genera or 17 species were documented in Socorro plateau, Goa and their phenological patterns such as flowering, fruiting and leaf cover were recorded and analysed. The phenological patterns of the individual trees were compared in relation to each other such as in-between flowering and fruiting of the same species. In addition to this, the species were compared with each other in terms of their rate of flowering/fruiting to observe their inter-connected variations. Prospects for future research were identified to further promote studies in conservation biology of flora and fauna in the area and in climate change to mediate its effects.

plant biology↗

bioRxiv2022

Astrocyte-Oligodendrocyte interaction regulates central nervous system regeneration

Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand1,2. Here, we show that interaction between glial cells - astrocytes and mature myelin-forming oligodendrocytes - is a critical determinant of remyelination. Astrocytes support the survival of regenerating oligodendrocytes, via downregulation of the Nrf2 pathway associated with increased astrocytic cholesterol biosynthesis pathway activation. Remyelination fails following sustained astrocytic Nrf2 activation yet is restored by either cholesterol biosynthesis/efflux stimulation, or Nrf2 inhibition using the existing therapeutic Luteolin. We identify that astrocyte-oligodendrocyte interaction regulates remyelination, and reveal a drug strategy for central nervous system regeneration centred on targeting this interaction.

neuroscience↗