Zhigang Miao

Soochow University (PRC) | SUDA · Institute of neuroscience

Epigenetic mechanisms such as DNA methylation and hydroxymethylation play a significant role in depression. This research has shown that Ten‐eleven translocation 2 (Tet2) deficiency prompts depression‐like behaviors, but Tet2's transcriptional regulation remains unclear. In the study, bioinformatics is used to identify nuclear receptor subfamily 2...

Stroke is a significant public health issue, and research has consistently focused on studying the mechanisms of injury and identifying new targets. As a CDK5 activator, p39 plays a crucial role in various diseases. In this article, we will explore the role and mechanism of p39 in cerebral ischemic injury. We measured the level of p39 using western...

Non-coding CGG repeat expansions within the 5′ untranslated region are implicated in a range of neurological disorders, including fragile X-associated tremor/ataxia syndrome, oculopharyngeal myopathy with leukodystrophy, and oculopharyngodistal myopathy. This review outlined the general characteristics of diseases associated with non-coding CGG rep...

Brain development requires a delicate balance between self-renewal and differentiation in neural stem cells (NSC), which rely on the precise regulation of gene expression. Ten-eleven translocation 2 (TET2) modulates gene expression by the hydroxymethylation of 5-methylcytosine in DNA as an important epigenetic factor and participates in the neurona...

The lateral habenula (LHb) has been considered a moderator of social behaviors. However, it remains unknown how LHb regulates social interaction. Here, we show that the hydroxymethylase Tet2 is highly expressed in the LHb. Tet2 conditional knockout (cKO) mice exhibit impaired social preference; however, replenishing Tet2 in the LHb rescues social p...

R-loop, an RNA-DNA hybrid structure, arises as a transcriptional by-product and has been implicated in DNA damage and genomic instability when excessive R-loop is accumulated. Although previous study demonstrated that R-loop is associated with ten-eleven translocation (Tet) proteins, which oxidize 5-methylcytosine to 5-hydroxymethylcytosine (5hmC),...

Introduction: Environmental stress promotes epigenetic alterations that impact gene expression and subsequently participate in the pathological processes of the disorder. Among epigenetic regulations, ten–eleven Translocation (Tet) enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA and RNA and function as critical playe...

Background Previous studies have shown that depression is often accompanied by an increase in mtDNA copy number and a decrease in ATP levels; however, the exact regulatory mechanisms remain unclear. Methods In the present study, Western blot, cell knockdown, immunofluorescence, immunoprecipitation and ChIP-qPCR assays were used to detect changes i...

Background Depression is one of the most common psychiatric diseases. The monoamine transmitter theory suggests that neurotransmitters are involved in the mechanism of depression; however, the regulation on serotonin production is still unclear. We previously showed that Ahi1 knockout (KO) mice exhibited depression-like behavior accompanied by a si...

Background Interleukin-18 (IL-18) may participate in the development of major depressive disorder, but the specific mechanism remains unclear. This study aimed to explore whether IL-18 correlates with areas of the brain associated with depression. Methods Using a case–control design, 68 subjects (34 patients and 34 healthy controls) underwent clin...

Phosphatidylserine (PS) is an anionic phospholipid in the eukaryotic membrane and is abundant in the brain. Accumulated studies have revealed that PS is involved in the multiple functions of the brain, such as activation of membrane signaling pathways, neuroinflammation, neurotransmission, and synaptic refinement. Those functions of PS are related...

Depression is one of the common psychiatric diseases worldwide. Previous studies showed that chronic stress could increase defecation and inhibit weight gain; however, the effects of chronic stress on gastrointestinal peristalsis had not been clarified. To study the mechanisms of depression, chronic restraint stress (CRS) is widely used as a tradit...

5-Hydroxymethylcytosine (5hmC) has recently been found that plays an important role in many diseases; however, there are still few studies in the field of stroke. The purpose of this review is to introduce the influence and function of 5hmC in stroke, in order for more people can study it. In this review, we introduced the role of 5hmC in ischemia...

Interleukin‐18 (IL‐18), a pro‐inflammatory cytokine, is thought to be associated with inflammation in many neurological diseases such as ischemic stroke and poststroke depression, but the role of IL‐18 in inflammatory injury after intracerebral hemorrhage (ICH) remains unclear. In this study, we established the ICH model in male mice and found that...

Background: Interleukin-18 (IL-18) may participate in the development of major depressive disorder, but the specific mechanism remains unclear. This study aimed to explore whether IL-18 correlates with areas of the brain associated with depression. Methods: Using a case-control design, 68 subjects (34 patients and 34 healthy controls) underwent cli...

βII spectrin (β2SP) is encoded by Sptbn1 and is involved in the regulation of various cell functions. β2SP contributes to the formation of the myelin sheath, which may be related to the mechanism of neuropathy caused by demyelination. As one of the main features of cerebral ischemia, demyelination plays a key role in the mechanism of cerebral ische...

Obesity has been followed with interest as a risk factor for COVID-19, with triglycerides as one of four common criteria used to define obesity, which have been used to study the mechanism of obesity. In this study, we showed that angiotensin-converting enzyme-2 (ACE2) is widely expressed in the mouse body, including the kidney, spleen, brain, hear...

Major depression disorder (MDD) is one of the most common psychiatric diseases. Recent evidence supports that environmental stress affects gene expression and promotes the pathological process of depression through epigenetic mechanisms. Three Ten-Eleven Translocation (Tet) enzymes are epigenetic regulators of gene expression that promote 5-hydroxy...

Objective: Through TTC staining, immunohistochemical analysis, RT-PCR and hind limb motor function evaluation and other experimental methods, to explore the regulatory mechanism of metformin on anti-apoptosis in rats with spinal cord injury (SCI). Methods: Establish a rat spinal cord injury model. Through Basso-Beattie -Bresnahan locomotor rating s...

C-type lectin–like receptor 2 (CLEC-2) is a platelet surface–activating receptor with the prominent involvement in platelet activation, which was found to be associated with the progression and prognosis of acute ischemic stroke patients. Although podoplanin is the only known endogenous ligand for CLEC-2, the role of podoplanin/CLEC-2 in cerebral i...

Radiation-induced cognitive dysfunction is a common complication associated with cranial radiation therapy. Inhibition of hippocampal neurogenesis and proliferation plays a critical role in this complication. Relieving hippocampal apoptosis may significantly protect hippocampal neurogenesis and proliferation. Previous studies have demonstrated that...

Stress activates the nuclear translocation of glucocorticoid receptors (GR) to trigger gene expression. Abnormal GR levels can alter the stress responses in animals and therapeutic effects of antidepressants. Here, we reported that stress-mediated nuclear translocation of GR reduced Ahi1 in the stressed cells and mouse brains. Ahi1 interacts with G...

Poststroke depression (PSD) is a common complication of stroke and has long been a serious threat to human health. PSD greatly affects neurological recovery, quality of life and mortality. Recent studies have shown that 5-hydroxymethylcytosine (5hmC), an important epigenetic modification, is enriched in the brain and associated with many neurologic...

The major biological function of the sperm cell is to transmit the paternal genetic and epigenetic information to the embryo as well as the following offspring. Sperm has a unique epigenome. An increasing body of epidemiological study supports that paternal stress induced by environmental exposures and lifestyle can modulate the sperm epigenome (in...

Objective To investigate the prevalence of posttraumatic stress symptoms (PTSS) of health care workers (HCWs) who were potentially or directly exposed to patients with coronavirus disease 2019 (COVID-19) in a non-core epidemic area of China. Methods Psychological conditions were evaluated by the multiple psychological evaluation scales in HCWs at...

Background: The rapidly increasing case reports revealed that neuronal intranuclear inclusion disease (NIID) had concomitant other system symptoms besides nervous system symptoms. In this study, we systematically evaluated the symptoms, signs, auxiliary examination, and pathological changes in different systems in NIID patients. Methods: NIID pa...

Post-stroke depression (PSD) is a common and serious complication that affecting one third of stroke patients for poor quality of life, high mortality, high recurrent rate, and slow recovery. Recent studies showed that serum interleukin-18 (IL-18) level is a biomarker for patients with PSD. However, the role of IL-18 in the pathology of PSD is stil...

Aim: Roles of forced running exercise (FE) in remediation of neurogenesis inhibition and radiation-induced cognitive dysfunction were investigated in a whole-brain irradiation mice model via the regulation of DNA 5-hydroxymethylation modification (5 hmC) and its catalytic enzymes ten-eleven translocation (Tet) proteins. Materials & methods: Hippoca...

Depression is a serious global affective disorder and one of the most common neurological diseases. Tanshinone IIA (TSA) is the mainly active constituent of Salvia miltiorrhiza and has diverse biological effects, including anti-inflammatory and antioxidant effects and significant neuroprotective effects against cerebral ischemia and Alzheimer's dis...

Cystatin C, a well‐established biomarker of renal function, has been associated with a protective effect against stroke. However, the potential neuroprotective mechanism of cystatin C in ischemic brain injury remains unclear. Our study hypothesized that cystatin C can ameliorate blood–brain barrier (BBB) disruption by up‐regulating caveolin‐1 expre...

Aim: We aim to study the antidepressant mechanism of metformin. Materials & methods: Tail suspension test and forced swimming test were used to detect the depression-like behavior; the expressions of target protein were examined by western blot; the levels of target genes were tested by quantitative PCR; the content of α-ketoglutarate and 5hmC were...

5-hydroxymethylcytosine (5hmC) is enriched in brain and has been recognized as an important DNA modification. However, the roles of 5hmC and its writers, ten-eleven translocation (Tet) proteins, in stress-induced response have yet to be elucidated. Here, we show that chronic restraint stress (CRS) induced depression-like behavior in mice and result...

Aim: Roles of DNA 5-hydroxymethylcytosine (5hmC) in myelin repair were investigated in an experimental autoimmune encephalomyelitis (EAE) mouse model via its regulation on brain-derived neurotrophic factor (BDNF). Methods: DNA 5hmC level and its limiting enzymes were detected in EAE mice. Results: Global 5hmC modification, Tet1 and Tet2 signif...

Spinal cord injury (SCI) is a serious neurological disease, often leading to segmental injury following severe limb dysfunction. Recent studies showed that epigenetic regulation is involved in the pathogenesis of SCI. In this study, we examined the change in 5-hydroxymethylcytosine (5hmC), a mechanism of demethylation, and its role in SCI in rats....

5‐Hydroxymethylcytosine (5hmC) exists in DNA, RNA, and mitochondrial DNA (mtDNA) and plays an important role in many diseases. Specifically, 5hmC is involved in promoting gene expression, and this process is regulated by Tet enzymes. In this study, we identified that there is no difference in male mice and female mice at first; then we examined the...

Previous studies have demonstrated that plasma resistin levels were increased in patients with acute ischemic stroke. However, the role of resistin after ischemic brain injury is still unclear. In this study, we investigated the protective effects of resistin on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model....

Mixed lineage kinase domain-like (MLKL) protein was recently found to play a critical role in necrotic cell death. To explore its role in neurological diseases, we measured MLKL protein expression after ischemia injury in a mouse model. We found that MLKL expression significantly increased 12 h after ischemia/reperfusion (I/R) injury with peak leve...

Epigenetics regulation has been considered a mechanistic interface between environmental stress stimuli and altered functioning of underlying gene network. Metabolite changes in vivo after stress contribute to histone modification. Histone3-lysine9-β-hydroxybutyrylation (H3k9bhb), a novel histone modification mark induced by β-hydroxybutyrate, may...

Purpose: Fabry disease is an X-linked genetic disorder caused by the mutations of alpha-galactosidase A (GLA, MIM 300644) gene presenting with various clinical symptoms including small-fiber peripheral neuropathy and limb burning pain. Here, we reported a Chinese pedigree with the initial diagnosis of primary erythromelalgia in an autosomal domina...

5-hydroxymethylcytosine (5hmC) is considered as a novel DNA modification and plays an important role in cancer, stem cells, and developmental diseases. In this study, we demonstrated the existence of RNA 5hmC modification in mouse brain RNA by using a dot blot analysis method. Our data indicated that 5hmC modification in RNA samples was less than t...

Post stroke depression (PSD) is one of the most common complications of ischemic stroke. At present, the underlying mechanisms are unclear, largely because there are no reliable, valid and reproducible animal models of PSD. Here we report a novel animal model of PSD that displays consistent and reliable clinical features of hemiplegic stroke. The a...

Epigenetic modifications such as cytosine methylation and histone modification are linked to the pathology of ischemic brain injury. Recent research has implicated 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine (5mC) via oxidation by ten-eleven translocation (Tet) enzymes, in DNA methylation-related plasticity. Here we sho...

Connexin43 (Cx43) is one of the most abundant gap junction proteins in the central nervous system. Abnormal opening of Cx43 hemichannels after ischemic insults causes apoptotic cell death. In this study, we found persistently increased expression of Cx43 8 h to 7 d after hypoxia/ischemia (HI) injury in neonatal rats. Pre-treatment with Gap26 and Ga...

7,8-Dihydroxy-4-methylcoumarin (Dhmc) is a precursor in the synthesis of derivatives of 4-methyl coumarin, which has excellent radical scavenging properties. In this study, we investigated whether Dhmc protects against oxidative stress and ischemic brain injury. We found that Dhmc protected against glutamate toxicity in hippocampal HT-22 cells in a...

Cystatin C (CysC) has been used as a renal function indicator and a strong predictor of cardiovascular events. In this study, we determined the prognostic value of serum CysC in patients with acute ischemic stroke (AIS) and examined its protective role on ischemic brain injury. First-ever stroke patients (601 cases) and control subjects (325 cases)...

Recent studies indicate that over-activation of Cdk5 is a crucial pro-death signal and Cdk5 activity inhibition provides neuroprotection in animal stroke models. However, Cdk5 inhibitors are reported to affect physiological functions of Cdk5 and lead to serious side effects. Therefore, targeting Cdk5 or its activators without affecting physiologica...

Oligodendrocytes are the predominant cell type in white matter and are highly vulnerable to ischemic injury. The role of oligodendrocyte dysfunction in ischemic brain injury is unknown. In this study, we used a 24-amino acid peptide S14G-Humanin (HNG) to examine oligodendrogenesis and neurological functional recovery in a hypoxic/ischemic (H/I) neo...

White matter tracts are composed of axons and myelinating oligodendrocytes. Oligodendrocytes are the myelinating cells in the central nervous system that allow formation of myelin and saltatory nerve conduction. Cerebral white matter is highly vulnerable to ischemic injury in adults and neonates. White matter injury in newborn brains results in cer...

Major depression is becoming one of the most prevalent forms of psychiatric disorders. However, the mechanisms of major depression are still not well-understood. Most antidepressants are only effective in some patients and produce some serious side effects. Animal models of depression are therefore essential to unravel the mechanisms of depression...

Daphnetin (DAP), a coumarin derivative, has been reported to have multiple pharmacological actions including analgesia, antimalarial, anti-arthritic, and anti-pyretic properties. It is unclear whether DAP has neuroprotective effects on ischemic brain injury. In this study, we found that DAP treatment (i.c.v.) reduced the infarct volume at 24 h afte...

Apelin is an endogenous ligand of G protein-coupled receptor -apelin and angiotensin-1-like receptor (APJ). The biological effects of apelin-APJ system are reported in multiple systems including cardiovascular, endocrinal, and gastrointestinal system. Previous studies had shownthat apelin-13 is a potential protective agent on cardiac ischemia; howe...