Neuroscience in China: Domestic and Foreign Experts Working Together

This Journal of Neurochemistry Special Issue is a collection of eight published, peer-reviewed articles titled “Neuroscience in China: Experts working together on the nervous system in health and disease.” Six of these contributions are reviews, and two are original research papers. Here, we provide a brief overview of affairs in Chinese neuroscience, followed by an introduction to the current contributions. China contributed nearly one-third of the academic papers published in the most influential international journals in 2022 and has overtaken the United States as the number one ranked country for contributions to research articles published in the Nature Index group of high-quality natural science journals (Baker 2023; Wagner et al. 2022). The Chinese government has earmarked neuroscience as a field of excellence. Basic neuroscience research, as well as translational research for the diagnosis and intervention of brain diseases, prioritized governmental support via The China Brain Project (Poo et al. 2016), a 15-year mission approved by the Chinese National People's Congress in March 2016. Furthermore, the Chinese government promotes research involving partnerships between high-profile domestic and foreign (by nationality) experts working side-by-side in China. For example, the editors of this very Special issue represent one such team at Zhejiang Chinese Medical University, led by Zhong Chen for the domestic group, a member of which is Yi Wang, and by Vladimir Parpura for the foreign group, a member of which is Vedrana Montana. This type of collaborative approach can be promoted by the so-called “111 Plan”, which is jointly organized and implemented by the Ministry of Education and the State Administration of Foreign Experts Affairs (Li 2006). The intent of the Special issue is to illustrate a subset of neuroscience topics investigated by scholars in China, domestic and foreign (by nationality) working together, along with their collaborators abroad. We now introduce the 8 papers in this Special Issue that fulfill this expectation. Zebrafish (Danio rerio) is widely used as a model organism in neuroscience research because of its genetic similarity to humans, rapid development and practical laboratory advantages, including cost effectiveness (Siddiqui et al. 2025). This organism represents an ethical alternative to mammalian models, as it complies with the three Rs (reduce, refine and replace) of animal research, the principles conceptualized by Russell and Burch (1959). In this Special Issue, Jiang et al. (2025) overview the use of zebrafish as a promising model for studying epitranscriptomic regulation of the central nervous system (CNS). This phenomenon involves chemical modifications of RNA, which affect RNA location, stability and processing and play a role in brain development and physiology, as well as in a wide variety of pathologies, including neurodevelopmental, neurodegenerative and psychiatric disorders, and brain tumors (Zhang et al. 2024). Jiang et al. (2025) discuss the types of RNA modifications and the role of epitranscriptomics in zebrafish CNS processes and behavioral regulation, along with the applicability of this organism for modeling various human brain disorders. They highlight the importance of understanding how environmental factors affect RNA modifications in the zebrafish brain, as such knowledge may assist in the identification of novel targets for intervention in human diseases. The authors also propose a list of selected open questions/challenges and future research directions in this niche of molecular neurochemistry. In addition to neurons, the nervous system is home to neuroglia, a diverse population of cells derived from dual origins, the ectoderm (astroglia and oligodendroglia) and the mesoderm (microglia); these nonneuronal cells mainly maintain homeostasis (water, ions, transmitters, metabolites, etc.) and provide protection (e.g., against microbial organisms, etc.) of the nervous system (Verkhratsky, Ho, et al. 2019). Neuroglia exhibit changes during aging (Verkhratsky, Zorec, et al. 2019), increase cognitive longevity (Zorec et al. 2025), and play a role in virtually all disorders and diseases of the nervous system (Scuderi et al. 2021; Li et al. 2021; Verkhratsky, Zorec, et al. 2019). In this Special Issue, Verkhratsky et al. (2025) update on newly established roles of neuroglia in: (i) development, whereby astrocytic perivascular endfeet control the cessation of oligodendrocyte precursor cells (OPCs) migration along the blood vessels and the detachment of OPCs from vasculature, leading to the initiation of their differentiation into myelinating oligodendrocytes (Su et al. 2023); (ii) physiology, whereby ependymal glia play a role in the CNS–body volume transmission, i.e., regulate cerebrospinal fluid flow from the spinal cord to peripheral tissues via spinal nerves (Li et al. 2024); (iii) neuroprotection, which is provided by astrocytic extracellular vesicles containing apolipoprotein E in neuromyelitis optica, a rare autoimmune disease (Jiang et al. 2024); (iv) stress-induced depressive behaviors in mice whereby the overexpression or knockdown of astrocytic ezrin, which defines peripheral astrocyte process plasticity (Lavialle et al. 2011), provides for resilience or vulnerability to stress, respectively (Lin et al. 2026); (iv) schizophrenia, whereby hypertrophic OPCs, having increased alternative splicing of DISC1 exon 3 (DISC1-Δ3), can be found in postmortem human patient's brain tissue, while schizophrenia-like behavior can be rendered in mice harboring experimentally induced hypertrophic OPCs due to overexpression of the alternative splice variant DISC1-Δ3, along with displaying the consequential overactivation of Wnt/β-catenin signaling pathway in these cells (Yu et al. 2022); and (v) pathology of APP-PS1 mouse, a preclinical model of Alzheimer's disease harboring both amyloid peptide (APP) Swedish mutation and presenilin 1 (PS1) delta 9 mutation, which is mediated by astrocytic and microglial connexin 43 hemichannels, i.e., unpaired connexons, the opening of which creates a vitious cycle of autocrine glutamatergic and ATPergic activity leading to excitotoxity and neuroinflammation; the authors also discuss a newly formulated lipid nanoparticle-encapsulated connexin 43 hemichannel peptidergic inhibitor, which showed increased blood–brain barrier penetration and brain retention in mice, along that it rescued cognitive deficits, reduced neuroinflammation, and, when administered early, decreased β-amyloid plaque build-up in APP-PS1 mice (Su et al. 2024). Astroglia undergo a process of reactive astrogliosis in response to brain disorders and lesions of various etiologies (see table 1 of reference (Verkhratsky et al. 2021)). The understanding of this process has been dynamically evolving; it has been reviewed on multiple occasions, and guidelines for its nomenclature, definitions and future directions have been issued (Escartin et al. 2021). There are several in parallel classifications of astrogliosis, and for the brevity of this editorial, we take a hybrid approach by combining various classifications. On the basis of cell morphology, astrogliosis can be classified as follows: (i) isomorphic, whereby astrocytes become hypertrophic but neither proliferate nor show motility, and their morphology is restored after the resolution of pathology; (ii) anisomorphic, whereby astrocytes proliferate, migrate toward the lesion site and take part in the formation of the so-called “glial scar” (the term that should be treated as obsolete), contemporary referred to as the perilesional reactive glia barrier, an irreversible dense collection of extracellular components and various cell types, primarily reactive astrocytes. In health and during astrogliosis, astrocytes are molecularly and morphologically heterogeneous (Endo et al. 2022; Clayton and Liddelow 2025). Among them, so-called neurotoxic astrocytes (also known as A1 reactive astrocytes) can secrete neurotoxic factors that can cause neuronal damage and death (Guttenplan et al. 2024; Liddelow et al. 2017). In this Special Issue, Paveliev et al. (2025) provide an overview of reactive astrogliosis in response to neuroimplants, whereas Ye et al. (2025) present their original research on protection against neurotoxic astrocytes in epilepsy. Ever since the debate of bioelectricity was initiated by Luigi Galvani and Alessandro Volta, scientists have been trying to develop tools and devices that can interface with cells, such as neurons, that exhibit bioelectricity (Parpura 2012). Given that electrical signals are defective in the brain in a variety of conditions and diseases, attempts have been made to use brain–machine interfaces to understand brain function and to restore normalcy (Parpura 2008). However, the major obstacle originates from brain defense, most prominently represented by the formation of the glial barrier, in response to the implanted electrodes. Paveliev et al. (2025) review approaches, such as chondroitinase ABC treatment, chondroitin sulfate-binding peptides, stem cells and hydrogels, that can reduce the formation of the glial barrier. The authors also discuss most commonly used imaging techniques, including two-photon microscopy and optical coherence tomography, for neuroimplant research, along with a discussion of the quantitative analysis of glial cell morphology. In this Special issue, Ye et al. (2025) present their original research on reactive astrocytes in epilepsy. Astrocyte dysfunction plays a role in the initiation and progression of epilepsy (Vezzani et al. 2022). However, less is known about the molecular subtypes of reactive astrocytes that may contribute to the etiology of epilepsy. Ye et al. describe the presence of neurotoxic A1 reactive astrocytes in a kainic acid (KA)-induced mouse model of epilepsy as well as in ex vivo human brain tissue from patients with temporal lobe epilepsy (TLE). On the basis of mouse and human brain tissue transcriptomics and lipidomics analyses, neurotoxic reactive astrocytes are likely to induce neuronal damage through the release of toxic lipids. The anticonvulsant cannabidiol (CBD) suppressed the formation of neurotoxic reactive astrocytes in cell culture and mitigated seizure progression in KA-induced epileptic mice, which also resulted in enhanced cognitive function upon CBD treatment; similar effects were observed when ZM241385, an adenosine A2A receptor (A2AR) antagonist, was used. Specifically, A2AR is a molecular marker enriched in reactive astrocytes (Vezzani et al. 2022), a finding confirmed in the present study; CBD downregulated A2AR expression in neurotoxic reactive astrocytes in culture and inhibited the lipid-releasing activity of these cells. A corollary to this study is that CBD might be useful in the treatment of TLE. If so, that could mean an expansion of the already approved clinical use of CDB under the sole human preparation/label of Epidiolex. At present, in the US, Epidiolex is used for the treatment of seizures associated with Dravet syndrome, Lennox–Gastaut syndrome or tuberous sclerosis complex in people who are 1 year of age and older (Elliott et al. 2020). Early-life seizures (ELSs) occur in the first year of life and represent a noteworthy concern in pediatric neurology; they are the most common neurological emergencies in neonates (Samanta 2021). ELSs have an assorted etiology associated with multiple codes in the International Classification of Diseases, Eleventh Revision, and Clinical Modification (ICD-11-CM). ELS can result in long-lasting impairments; thus, understanding the effects of ELS on brain connectivity/circuitry is important for the development of preventive strategies and targeted therapies. With respect to this Special issue, Wang et al. (2025) discuss exactly that. At the onset, the authors provide a comprehensive list of animal models to study ELS, in particular those induced by febrile seizures, chemoconvulsants and hypoxia. The mechanisms of ELS-induced adult epileptogenesis are as follows: (i) the enhancement of excitatory and the waning of inhibitory synaptic transmission, with consequential changes in neural networks, particularly maladaptive plasticity; (ii) inflammatory responses; and (iii) aberrations in metabolism. Biomarkers for ELS-induced adult epileptogenesis clearly need to be developed, as do ELS-modifying therapeutic strategies, not only to treat various forms of ELS but also to prevent its long-term sequelae, which include increased susceptibility to seizures in adulthood. The hallmark of many neurodegenerative diseases, the two most common being Alzheimer's disease and Parkinson's disease, is protein aggregation and accumulation. Aggregated proteins disrupt cellular functions and contribute to neuronal loss (Lee et al. 2011). In this Special Issue, Ho (2025) provides an overview of the accumulation of α-synuclein aggregates found in Lewy bodies in Parkinson's disease. Although pathologically relevant, the mechanisms of aggregate elimination are not clear. The author presents rodent and fly (N.B., another complier to 3Rs and hence an ethical alternative to mammals) models of Parkinson's disease followed by a description of neuronal and glial, the latter astrocytic and microglial, α-synuclein degradation pathways. Glial cells are emerging as key players in the degradation of α-synuclein, indicating the possibility for novel therapeutic strategies to increase glial-mediated degradation, which in turn could provide neuroprotection and curtail the progression of this pathology. Demyelinating diseases are disorders in which the myelin sheet, made out of mature oligodendrocytes (OLs) in the CNS, is damaged, resulting in the disruption of axonal conduction and the display of subsequent neurological symptoms. Remyelination in the CNS has been a formidable challenge. A possible therapeutic solution is to obtain replacement OLs through their differentiation from OPCs residing in the CNS. OPCs can be identified molecularly as neuron-glial antigen 2 (NG2; also termed chondroitin sulfate proteoglycan 4 or melanoma-associated chondroitin sulfate proteoglycan) and platelet-derived growth factor receptor A (PDGFA; also termed CD140a)-positive cells (Nishiyama et al. 2009). In this Special issue, Liu et al. (2025) prepared OPCs using a cross of genetically modified mice, in which NG2 cells were tagged with green fluorescence protein, and immune panning was performed using an antibody against PDGFA. They repurposed ospemifene, a selective estrogen receptor modulator (SERM) that is otherwise clinically used to treat postmenopausal women who experienced vaginal dryness and dyspareunia. The rationale behind the repurposing of ospemifene is twofold: (i) SERMs may regulate OPC differentiation and myelination (Chen et al. 2019; Rankin et al. 2019), and (ii) ospemifene has minimal side effects in clinical use with sufficient predicted blood–brain barrier permeability (Pietrzak et al. 2023). Indeed, ospemifene promoted (i) the differentiation of purified mouse OPCs to OLs when the OPCs were grown on a planar substrate in culture and (ii) the wrapping of OLs around the nanofibers, with the latter used to structurally emulate axons (Vijayakumar and Rathinam 2025). Moreover, ospemifene promoted myelinogenesis and functional recovery in animal models of demyelination (i) due to hypoxia, which reduced OPC differentiation and myelination in the neonatal brain; (ii) in experimental autoimmune encephalomyelitis; and (iii) induced by lysophosphatidylcholine. Should ospemifene prove to be as effective in human clinical trials as in these preclinical translational studies, it may be approved as an off-label drug for use in treating demyelinating diseases. Glioblastomas (GBMs) are the most common primary malignant brain tumors in adults. They are among the deadliest cancers, with a median survival of 14 months despite the use of standard-of-care (surgery, radiotherapy, and chemotherapy with temozolomide) (Hottinger et al. 2014; Stupp et al. 2009). GBMs are characterized by extensive dispersal throughout the brain, which is indicative of their highly invasive nature (Zagzag et al. 2008). GBMs originate from astrocytes and are classified as a subset of grade IV astrocytoma expressing the wild-type enzyme isocitrate dehydrogenase (IDH) (Weller et al. 2021). The identification of treatments that stop or attenuate the progression of GBM is life altering. This is the very subject explored in this Special issue by Yang et al. (2025). In addition to providing an overview of standard-of-care therapy, the authors discuss the following novel therapeutic approaches for the treatment of GBM: (i) tumor-treating fields that deliver nonionizing low-intensity alternating electric fields to disrupt mitosis; (ii) molecular targeted therapies that inhibit specific gene mutations or signaling pathways; (iii) immunotherapy that activates the patient's own immune system to fight GBM; (iv) proton therapy, which minimizes damage to the normal brain parenchyma surrounding the GBM because of its precise radiation dose distribution; (v) oncolytic virus therapy to selectively infect and lyse GBM cells; and (vi) the use of nanoparticle carriers for targeted drug delivery to increase therapeutic efficacy and reduce side effects; (vii) phototherapy; and (viii) sonodynamic therapy. As GBM treatment advances, more personalized, precise, effective treatment options should become available. Notably, GBMs are truly human pathologies, making them difficult to experimentally study. In human patients, the age-standardized incidence rate is approximately 3.19 cases per 100 000 individuals in the United States (Price et al. 2024) and approximately 1.0 cases per 100 000 individuals in China (Woo et al. 2022). Naturally occurring GBM in nonhuman primates is extremely rare (Simmons and Mattison 2011). However, GBMs naturally occur in dogs, with an estimated incidence of ~0.4 per 100 000 from in reference et al. GBMs exhibit the of human GBM thus, could be and the only animal model for novel for this et al. Moreover, human GBM the preclinical model for in and in vivo the latter by in the of mice et al. 2011). have molecular subtypes et al. of be the use of human GBM cell (e.g., and which have (Li et al. and can be grown term in cell culture et al. the is that they have been for in in which they have rodent GBM cell should be at all as they do not represent human pathology to their For in mice, cells were induced by the highly et al. whereas in cells were and from malignant in the brain et al. the eight papers in this Special Issue provide a of neuroscience research in China. this issue is the of the of Chinese neuroscience to the field and of Vedrana review and Yi review and Zhong review and Vladimir original review and is an at the of The authors of The authors have to