Chihye Chung

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Verified

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• PhD
• Professor (Full) at Konkuk University

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social interaction deficits and repetitive behaviors. While precise causes of ASD remain elusive, growing evidence highlights that an imbalance in excitatory and inhibitory (E/I) signaling is a pivotal factor in ASD development and modulation. Balanced E/I neurotransm...

Central melanocortin signaling plays a critical role in maintaining energy homeostasis by regulating energy intake and expenditure, with impairment of this system closely related to metabolic diseases such as obesity. Among melanocortin receptor subtypes, melanocortin receptor 4 (MC4R) is the primary mediator of these effects within the central ner...

The prevalence of depressive disorders in women has been reported in many countries. However, the cellular mechanisms mediating such sex differences in stress susceptibility remain largely unknown. Previously, we showed that lateral habenula (LHb) neurons are more activated in female mice than in male mice by restraint stress. Given the important r...

Emerging evidence suggests that the enhanced activity of lateral habenula (LHb) is involved in depressive disorders. This abnormal potentiation of LHb neurons was shown to originate from presynaptic alterations; however, the mechanisms underlying this presynaptic enhancement and physiological consequences are yet to be elucidated. Previously, we re...

Synaptic plasticity in the amygdala plays an essential role in the formation and inhibition of fear memory; however, this plasticity has mainly been studied in the lateral amygdala, making it largely uninvestigated in other subnuclei. Here, we investigated long-term potentiation (LTP) and long-term depression (LTD) in the basolateral amygdala (BLA)...

Depression is twice as prevalent in women as in men, however, most preclinical studies of depression have used male rodent models. This study aimed to examine how stress affects metabolic profiles depending on sex using a rodent depression model: sub-chronic variable stress (SCVS). The SCVS model of male and female mice was established in discovery...

The lateral habenula (LHb) is a well-established brain region involved in depressive disorders. Synaptic transmission of the LHb neurons is known to be enhanced by stress exposure; however, little is known about genetic modulators within the LHb that respond to stress. Using recently developed molecular profiling methods by phosphorylated ribosome...

Depressive disorders are more prevalent and severe in women; however, our knowledge of the underlying factors contributing to female vulnerability to depression remains limited. Additionally, females are notably underrepresented in studies seeking to understand the mechanisms of depression. Various animal models of depression have been devised, but...

Small humanin-like peptide 2 (SHLP2) is a mitochondrial-derived peptide implicated in several biological processes such as aging and oxidative stress. However, its functional role in the regulation of energy homeostasis remains unclear, and its corresponding receptor is not identified. Hereby, we demonstrate that both systemic and intracerebroventr...

The lateral septum (LS) is a forebrain structure that has been implicated in a wide range of behavioral and physiological responses to stress. However, the specific populations of neurons in the LS that mediate stress responses remain incompletely understood. Here, we show that neurons in the dorsal lateral septum (LSd) that express the somatostati...

E3 ubiquitin ligase, HOIL1-interacting protein (HOIP), forms the linear ubiquitin chain assembly complex (LUBAC) with HOIL and SHANK-associated RH domain interactor and catalyzes linear ubiquitination, directly linking the N- and C-termini of ubiquitin. Recently, several studies have implicated linear ubiquitination in aging and Alzheimer disease (...

FK501 binding protein 51 (FKBP5) is a stress response prolyl isomerase that inhibits the translocation of the glucocorticoid receptor (GR) heterocomplex to the nucleus. Previous studies have shown that the expression levels of FKBP5 are positively correlated with psychiatric disorders, including depression and post-traumatic stress disorder. In rod...

Mood disorders are more prevalent and often reported to be more severe in women; however, little is known about the underlying mechanisms of this sexual prevalence. To gain insight into the functional differences in female brains in response to stress, we systemically compared brain activation in male and female C57BL/6N mice after acute stress exp...

As global plastic production continues to grow, microplastics released from a massive quantity of plastic wastes have become a critical environmental concern. These microplastic particles are found in a wide range of living organisms in a diverse array of ecosystems. In this study, we investigated the biological effects of polystyrene nanoplastic (...

The habenula (Hb) has been hypothesized to play an essential role in major depressive disorder (MDD) as it is considered to be an important node between fronto-limbic areas and midbrain monoaminergic structures based on animal studies. In this study, we aimed to investigate the differences in volume and T1 value of the Hb between patients with MDD...

Rapid eye movement (REM) sleep is implicated learning and memory (L/M) functions and hippocampal long-term potentiation (LTP). Here, we demonstrate that REM sleep deprivation (REMSD)-induced impairment of contextual fear memory in mouse is linked to a reduction in hexosamine biosynthetic pathway (HBP)/O-GlcNAc flux in mouse brain. In mice exposed t...

As global plastic production continues to grow, microplastics released from a massive quantity of plastic wastes have become a critical environmental concern. These microplastic particles are found in a wide range of living organisms in a diverse array of ecosystems. In this study, we investigated the biological effects of polystyrene nanoplastics...

Inositol phosphate metabolism has emerged as one of the key players in synaptic transmission. Previous studies have shown that the deletion of inositol hexakisphosphate kinase 1 (IP6K1), which is responsible for inositol pyrophosphate biosynthesis, alters probability of presynaptic vesicle release and short-term facilitation of glutamatergic synaps...

Exposure to stress activates glucocorticoid receptors in the brain and facilitates the onset of multitude psychiatric disorders. It has been shown that FK506 binding protein 51 (FKBP5) expression increases during glucocorticoid receptor (GR) activation in various brain regions including the medial prefrontal cortex (mPFC). FKBP5 knockout (KO) mice...

Neuropeptide Y (NPY) is one of peptide neuromodulators, well known for orexigenic, anxiolytic and antidepressant effects. We previously reported that NPY decreases GABAergic transmission in the lateral habenula (LHb). In the current study, we aim to investigate the underlying signaling pathways that mediate NPY actions in the LHb by employing whole...

Depression is a devastating mental disorder affected by multiple factors that can have genetic, environmental, or metabolic causes. Although previous studies have reported an association of dysregulated glucose metabolism with depression, its underlying mechanism remains elusive at the molecular level. A small percentage of glucose is converted int...

The coordination of synaptic vesicle exocytosis and endocytosis supports neurotransmitter release from presynaptic terminals. While inositol pyrophosphates, such as 5-diphosphoinositol pentakisphosphate (5-IP7), are versatile signaling metabolites in many biological events, physiological actions of 5-IP7 on synaptic membrane vesicle trafficking rem...

129S1/SvImJ (S1) mice exhibit selective impairments in fear extinction, though the mechanisms underlying these impairments are not fully understood. The medial prefrontal cortex (mPFC) consists of the prelimbic cortex (PL) and infralimbic cortex (IL), which are known to be involved in fear conditioning and extinction, respectively. The PL and IL pr...

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and repetitive/restricted behaviors. Although gene-environment interactions may explain the heterogeneous etiology of ASD, it is still largely unknown how the gene-environment interaction affects behavioral symptoms and pathophysiology in...

Neuropeptide Y is a peptide neuromodulator with protective roles including anxiolytic and antidepressant-like effects in animal models of depression and post-traumatic stress disorder. The lateral habenula (LHb) is a brain region that encodes aversive information and is closely related with mood disorders. Although LHb neurons express NPY receptors...

Simultaneous expression of Oct4, Klf4, Sox2, and cMyc induces pluripotency in somatic cells (iPSCs). Replacing Oct4 with the neuro-specific factor Brn4 leads to transdifferentiation of fibroblasts into induced neural stem cells (iNSCs). However, Brn4 was recently found to induce transient acquisition of pluripotency before establishing the neural f...

129S1 mice show impaired extinction following auditory or contextual fear conditioning. (A) Experimental scheme for auditory fear conditioning and extinction. (B) Both C57BL/6 and 129S1 mice showed normal auditory fear conditioning across conditioning trials. 129S1 mice, however, exhibited impaired fear extinction following auditory fear conditioni...

Fear extinction diminishes conditioned fear responses and impaired fear extinction has been reported to be related to anxiety disorders such as post-traumatic stress disorder (PTSD). We and others have reported that 129S1/SvImJ (129S1) strain of mice showed selective impairments in fear extinction following successful auditory or contextual fear co...

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, featuring social communication deficit and repetitive/restricted behaviors as common symptoms. Its prevalence has continuously increased, but, till now, there are no therapeutic approaches to relieve the core symptoms, particularly social deficit. In previous studies, abnormal functio...

Recently, we have reported that animals with telomerase reverse transcriptase (TERT) overexpression exhibit reduced social interaction, decreased preference for novel social interaction and poor nest-building behaviors-symptoms that mirror those observed in human autism spectrum disorders (ASD). Overexpression of TERT also alters the excitatory/inh...

Nerve growth factor (NGF) exerts multiple functions on target neurons throughout development. The recent discovery of a point mutation leading toachangefromarginine totryptophanat residue100in thematureNGF;sequence (NGFR100W) inpatientswithhereditarysensoryand autonomic neuropathy type V (HSAN V) made it possible to distinguish the signaling mechan...

Nerve growth factor (NGF) exerts multiple functions on target neurons throughout development. The recent discovery of a point mutation leading to a change from arginine to tryptophan at residue 100 in the mature NGFβ sequence (NGF R100W ) in patients with hereditary sensory and autonomic neuropathy, type V (HSAN V), made it possible to distinguish...

Social interaction deficit is one of the hallmarks of autism spectrum disorders (ASD). Despite the spotlight in ASD diagnosis, social impairment still longs for a cure. The main reasons for the slow progress are the complexity of social behavior function and the heterogeneity of ASD etiology and pathophysiology. The excitatory-inhibitory imbalance...

Abnormal potentiation in the lateral habenula (LHb) has been suggested to mediate depression-like behaviors. However, the underlying mechanisms of the synaptic efficacy regulation of LHb synapses and the potential for their modulation are only poorly understood. Here, we report that long-term synaptic depression (LTD) occurs in the LHb upon both lo...

The lateral habenula (LHb) is a small part of the epithalamus that projects to monoamine centers in the brain. Previously, neurotransmission onto the LHb was shown to be abnormally potentiated in animal models of depression. However, synaptic plasticity in this brain area and the effect of stressor exposure on synaptic plasticity of the LHb have no...

Rhythmicity plays an important role in a number of biological systems. The habenular complex is reported to contain an intrinsic molecular clock and to show rhythmic expression of circadian clock genes and proteins including per2/PER2. In this study, we observed that there is a temporal rhythmicity in the presynaptic efficacy of the lateral habenul...

In addition to its classical role as a regulator of telomere length, recent reports suggest that telomerase reverse transcriptase (TERT) plays a role in the transcriptional regulation of gene expression such as β-catenin-responsive pathways. Silencing or over-expression of TERT in cultured NPCs demonstrated that TERT induced glutamatergic neuronal...

Significance Recent studies have implicated postsynaptic scaffolding protein synapse-associated protein 90/postsynaptic density protein 95-associated protein 3 (SAPAP3) or Shank3 in mood disorders such as bipolar disorder, autism, and obsessive-compulsive disorders. Neural Abelson-related gene-binding protein 2 (nArgBP2) is a binding partner of bot...

The hippocampus is vulnerable to uncontrollable stress and is enriched with oxytocin receptors, but their interactive influences on hippocampal functioning are unknown. This study aimed to determine the effects of intranasal oxytocin administration on stress-induced alterations in synaptic plasticity and spatial memory in male rats. While vehicle-a...

Influenza virus infection is one of common infectious diseases occurring worldwide. The human influenza virus can infect the central nervous system and cause brain dysfunctions affecting cognition and spatial memory. It has been previously shown that infection with the influenza viral protein within the hippocampus decreases Ca(2+) influx and reduc...

Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer's disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration cause...

Background: A number of neurological and neurodegenerative diseases share impaired cognition as a common symptom. Therefore, the development of clinically applicable therapies to enhance cognition has yielded significant interest. Previously, we have shown that activation of lysophosphatidic acid receptors (LPARs) via gintonin application potentia...

Lysophosphatidic acid (LPA) is one of the well characterized, ubiquitous phospholipids molecules. LPA exerts its effect by activating G-protein coupled receptors known as LPA receptors (LPARs). So far, LPAR signaling has been critically implicated during early development stages, including the regulation of synapse formation and the morphology of c...

Learning strategy preference was assessed in 5XFAD mice, which carry 5 familial Alzheimer's disease (AD) mutations. Mice were sequentially trained in cued and place/spatial versions of the water maze task. After training, a strategy preference test was conducted in which mice were required to choose between the spatial location where the platform h...

Neuroinflammation plays a key role in the initiation and progression of neurodegeneration in Alzheimer's disease (AD). Chronic neuroinflammation results in diminished synaptic plasticity and loss of GluN1 N-methyl-D-aspartate (NMDA) receptors in the hippocampus, leading to the cognitive deficits that are the most common symptoms of AD. Therefore, i...

The receptor for advanced glycation end products (RAGE) has been reported to have a pivotal role in the pathogenesis of Alzheimer's disease (AD). This study investigated RAGE levels in the hippocampus and cortex of a triple transgenic mouse model of AD (3xTg-AD) using western blotting and immunohistochemical double-labeling to assess cellular local...

Gintonin is a novel ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand. The primary action of gintonin is to elicit a transient increase in [Ca(2+)]i via activation of LPA receptor subtypes. Voltage-gated potassium (Kv) channels play important roles in synaptic transmission in nervous systems. The previous reports have sh...

Recent reports have proposed a novel function for the N-methyl-D-aspartate (NMDA) receptor (NMDAR), a well-known excitatory, ionotropic receptor. A series of observations employing pharmacological techniques has proposed that upon ligand binding, this ionotropic receptor can actually function via signaling cascades independent of traditional ionotr...

Central synapses operate neurotransmission in several modes: synchronous/fast neurotransmission (neurotransmitters are released quickly and release is tightly coupled to action potentials), asynchronous neurotransmission (neurotransmitter release is slower and longer lasting), and spontaneous neurotransmission (where small amounts of neurotransmitt...

Macelignan found in the nutmeg mace of Myristica fragrans obtains increasing attention as a new avenue in treating various diseases. Macelignan has been shown to possess a spectrum of pharmacological activities, including anti-bacterial, anti-inflammatory, anti-cancer, anti-diabetes, and hepatoprotective activities; recently, it has also been shown...

Previous studies have shown that the amygdala plays a key role in the modulation of uncontrollable stress effect on hippocampal long-term potentiation and memory in rats. This study aimed to determine the effects of selective neurotoxic lesions of the basolateral amygdala (BLA) on stress-induced glucocorticoid receptor (GR) translocation and altera...

Classical antidepressants elevate the monoamine levels in the brain by preventing re-uptake of monoamines after release. Treatment of depression with monoamine re-uptake inhibitors is associated with low clinical efficacy and remission rate due to the delayed onset of therapeutic responses. Therefore, the development of alternative antidepressants...

The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts...

Recent findings suggest that spontaneous neurotransmission is a bona fide pathway for interneuronal signaling that operates independent of evoked transmission via distinct presynaptic as well as postsynaptic substrates. This article will examine the role of spontaneous release events in neuronal signaling by focusing on aspects that distinguish thi...

Synapses maintain synchronous, asynchronous, and spontaneous forms of neurotransmission that are distinguished by their Ca(2+) dependence and time course. Despite recent advances in our understanding of the mechanisms that underlie these three forms of release, it remains unclear whether they originate from the same vesicle population or arise from...

Substantial insights into physical, chemical, and biological processes are attained by examining the properties of their elementary components, such as subatomic particles, atoms, and molecules. This analytical approach sometimes provides straightforward explanations for seemingly complex phenomena; however, quite often it leads to unexpected obser...

In a synapse, spontaneous and action-potential-driven neurotransmitter release is assumed to activate the same set of postsynaptic receptors. Here, we tested this assumption using (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (MK-801), a well characterized use-dependent blocker of NMDA receptors. NMDA-receptor-mediated...

Noncanonical secretagogues such as hypertonicity or alpha-latrotoxin have been extremely informative in studying neurotransmission. Lanthanum and lanthanides can also trigger neurotransmitter release through an unknown mechanism. Here, we studied the effect of lanthanides on neurotransmission in hippocampal cultures. Application of 2 mM La3+ caused...

During short-term synaptic depression, neurotransmission rapidly decreases in response to repetitive action potential firing. Here, by blocking the vacuolar ATPase, alkalinizing the extracellular pH, or exposing hippocampal slices to pH buffers, we impaired neurotransmitter refilling, and electrophysiologically tested the role of vesicle reuse in s...

A recent study proposes that the random and spontaneous, NMDA receptor-dependent miniature postsynaptic currents at hippocampal synapses serve to regulate local postsynaptic protein synthesis, thereby stabilizing synaptic function.