Traumatic injury to the spinal cord initiates a series of pathological cellular processes that exacerbate tissue damage at and beyond the original site of injury. This secondary damage includes oxidative stress and inflammatory cascades that can lead to further neuronal loss and motor deficits. Microglial activation is an essential component of these secondary signaling cascades. The voltage-gated

To prevent or delay the onset of Alzheimer’s disease (AD), we must understand its molecular basis. The great majority of AD cases arise sporadically with a late onset after 65 years of age (LOAD). However, rare familial cases of AD can occur due to dominant mutations in a small number of genes that cause an early onset prior to 65 years of age (EOfAD). As EOfAD and LOAD share similar pathologies and

Clathrin-mediated endocytosis plays an important role in the recycling of synaptic vesicle in presynaptic terminals, and in the recycling of transmitter receptors in neuronal soma/dendrites. The present study uses electron microscopy (EM) and immunogold EM to document the different categories of clathrin-coated vesicles (CCV) and pits (CCP) in axons compared to soma/dendrites, and the depolarization-induced

α2-Antiplasmin (α2AP), a principal physiological plasmin inhibitor, is mainly produced by the liver and kidneys, but it is also expressed in several parts of the brain, including the hippocampus and cerebral cortex. Our previous study demonstrated that α2AP knockout mice exhibit spatial memory impairment in comparison to wild-type mice, suggesting that α2AP is necessary for the fetal and/or neonatal

The comorbidities of depression and chronic pain have long been recognized in the clinic, and several preclinical studies have demonstrated depression-like behaviors in animal models of chronic pain. These findings suggest a common neuronal basis for depression and chronic pain. Recently, we reported that the mesolimbic dopaminergic system was tonically suppressed during chronic pain by enhanced inhibitory

Recombinant adeno-associated viruses (rAAVs), particularly those that permit efficient gene transfer to neurons from axonal terminals or across the blood–brain barrier, are useful vehicles for structural and functional studies of the neural circuit and for the treatment of many gene-deficient brain diseases that need to compensate for the correct genes in every cell in the whole brain. However, AAVs

Mutations in the Vacuolar protein sorting 35 (VPS35) gene have been linked to familial Parkinson’s disease (PD), PARK17. VPS35 is a key component of the retromer complex, which plays a central role in endosomal trafficking. However, whether and how VPS35 deficiency or mutation contributes to PD pathogenesis remain unclear. Here, we analyzed human induced pluripotent stem cell (iPSC)-derived neurons

The optokinetic response (OKR), a reflexive eye movement evoked by a motion of the visual field, is known to adapt its strength to cope with an environmental change throughout life, which is a type of cerebellum-dependent learning. Previous studies suggested that OKR learning induces changes in in-vivo spiking activity and synaptic transmission of the cerebellar Purkinje cell (PC). Despite the recent

Cerebral microinfarcts (MIs) lead to progressive cognitive impairments in the elderly, and there is currently no effective preventative strategy due to uncertainty about the underlying pathogenic mechanisms. One possibility is the dysfunction of GABAergic transmission and ensuing excitotoxicity. Dysfunction of GABAergic transmission induces excitotoxicity, which contributes to stroke pathology, but

Most individuals undergo traumatic stresses at some points in their life, but only a small proportion develop stress-related disorders such as anxiety diseases and posttraumatic stress disorder (PTSD). Although stress susceptibility is one determinant of mental disorders, the underlying mechanisms and functional implication remain unclear yet. We found that an increased amount of freezing that animals

Hypoxic-ischemic brain injury (HIBD) causes neonatal death and serious neurological disability; however, there are currently no promising therapies for it excepting cooling. Therefore, in this study, we used peptidome analysis to identify differentially expressed peptides in cerebrospinal fluid (CSF) of neonates with HIBD or controls, which may give a foundation for finding new promising drugs of neonatal

Increased neural activities reduced pH at the synaptic cleft and interstitial spaces. Recent studies have shown that protons function as a neurotransmitter. However, it remains unclear whether protons signal through a metabotropic receptor to regulate synaptic function. Here, we showed that GPR68, a proton-sensitive GPCR, exhibited wide expression in the hippocampus, with higher expression observed

Alzheimer’s disease (AD) is a highly prevalent neurodegenerative disease characterized by Aβ accumulation and tau hyperphosphorylation. Epidemiological evidence for a negative correlation between cancer and AD has led to the proposed use of tyrosine kinase inhibitors (TKIs) such as dasatinib and masitinib for AD, with reported beneficial effects in the AD brain. The TKI vatalanib inhibits angiogenesis

The goal of the present study was to elucidate the mechanism by which long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) promotes inflammation in Parkinson’s disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to induce PD development in C57BL/6 mice, and tyrosine hydroxylase (TH) expression was analysed by immunohistochemical analysis

Chronic pain alters cortical and subcortical plasticity, causing enhanced sensory and affective responses to peripheral nociceptive inputs. Previous studies have shown that ketamine had the potential to inhibit abnormally amplified affective responses of single neurons by suppressing hyperactivity in the anterior cingulate cortex (ACC). However, the mechanism of this enduring effect has yet to be understood

The amygdala plays an important role in the emotional-affective aspects of behaviors and pain, but can also modulate sensory aspect of pain (“nociception”), likely through coupling to descending modulatory systems. Here we explored the functional coupling of the amygdala to spinal nociception. We found that pharmacological activation of neurons in the central nucleus of the amygdala (CeA) increased

In the central nervous system, hyperpolarization-activated, cyclic nucleotide-gated (HCN1–4) channels have been implicated in neuronal excitability and synaptic transmission. It has been reported that HCN channels are expressed in the spinal cord, but knowledge about their physiological roles, as well as their distribution profiles, appear to be limited. We generated a transgenic mouse in which the

Dopamine is involved in many important brain functions, including voluntary motor movement. Dysfunction of the dopaminergic system can induce motor impairments, including Parkinson’s disease. We previously found that dopamine-deficient (DD) mice became hyperactive in a novel environment 72 h after the last injection of L-3,4-dihydroxyphenylalanine (L-DOPA) when dopamine was almost completely depleted

Frontotemporal dementia (FTD) is amongst the most prevalent early onset dementias and even though it is clinically, pathologically and genetically heterogeneous, a crucial involvement of metabolic perturbations in FTD pathology is being recognized. However, changes in metabolism at the cellular level, implicated in FTD and in neurodegeneration in general, are still poorly understood. Here we generate

Glutamate toxicity is a pathomechanism that contributes to neuronal cell death in a wide range of acute and chronic neurodegenerative and neuroinflammatory diseases. Activation of the N-methyl-D-aspartate (NMDA)-type glutamate receptor and breakdown of the mitochondrial membrane potential are key events during glutamate toxicity. Due to its manifold functions in nervous system physiology, however,

Variants of the cytoplasmic FMR1-interacting protein (CYFIP) gene family, CYFIP1 and CYFIP2, are associated with numerous neurodevelopmental and neuropsychiatric disorders. According to several studies, CYFIP1 regulates the development and function of both pre- and post-synapses in neurons. Furthermore, various studies have evaluated CYFIP2 functions in the postsynaptic compartment, such as regulating

Altered levels of brain-derived neurotrophic factor (BDNF) have been reported in neurologically diseased human brains. Therefore, it is important to understand how the expression of BDNF is controlled under pathophysiological as well as physiological conditions. Here, we report a method to visualize changes in BDNF expression in the living mouse brain using bioluminescence imaging (BLI). We previously

The release of dopamine (DA) into target brain areas is considered an essential event for the modulation of many physiological effects. While the anterior cingulate cortex (ACC) has been implicated in pain related behavioral processes, DA modulation of synaptic transmission within the ACC and pain related phenotypes remains unclear. Here we characterized a Crispr/Cas9 mediated somatic knockout of the

The transplantation of neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) has beneficial effects on spinal cord injury (SCI). However, while there are many subtypes of NPCs with different regional identities, the subtype of iPSC-derived NPCs that is most appropriate for cell therapy for SCI has not been identified. Here, we generated forebrain- and spinal cord-type

Cav3.2 T-type calcium channels are important mediators of nociceptive signaling, but their roles in the transmission of itch remains poorly understood. Here we report a key involvement of these channels as key modulators of itch/pruritus-related behavior. We compared scratching behavior responses between wild type and Cav3.2 null mice in models of histamine- or chloroquine-induced itch. We also evaluated

Repressor element 1-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a transcription repressor and its expression is regulated by the Wnt pathway through β-catenin. Metabotropic glutamate receptor 5 (mGluR5) signaling plays a key role in controlling neuronal gene expression. Interestingly, REST/NRSF nuclear translocation and signaling, as well as mGluR5 signaling are

Lateral habenula (LHb) is a brain region acting as a hub mediating aversive response against noxious, stressful stimuli. Growing evidences indicated that LHb modulates aminergic activities to induce avoidance behavior against nociceptive stimuli. Given overlapped neural circuitry transmitting pain and itch information, it is likely that LHb have a role in processing itch information. Here, we examined

Transition metals, such as iron, copper, and zinc, play a very important role in life as the regulators of various physiochemical reactions in cells. Abnormal distribution and concentration of these metals in the body are closely associated with various diseases including ischemic seizure, Alzheimer’s disease, diabetes, and cancer. Iron and copper are known to be mainly involved in in vivo redox reaction

Serotonin (5-HT) is a well-known modulator of behavioral, physiological, and emotional functions of the forebrain region. We recently discovered alterations of serotonergic synaptic modulations in both, the prefrontal cortex (PFC) and the somatosensory cortex, in the 15q dup mouse model of autism spectrum disorder (ASD). To further understand the roles of the 5-HT system implicated in developmental

MicroRNAs perform important roles in the post-transcriptional regulation of gene expression. Sequencing as well as functional studies using antisense oligonucleotides indicate important roles for microRNAs during the development of epilepsy through targeting transcripts involved in neuronal structure, gliosis and inflammation. MicroRNA-22 (miR-22) has been reported to protect against the development

As the main organelles for the clearance of damaged proteins and damaged organelles, the function of lysosomes is crucial for maintaining the intracellular homeostasis of long-lived neurons. A stable acidic environment is essential for lysosomes to perform their functions. TMEM175 has been identified as a new K+ channel that is responsible for regulating lysosomal membrane potential and pH stability

A unique feature of fear memory is its persistence that is highly relevant to fear and anxiety-related mental disorders. Recurrent reactivation of neural representations acquired from a traumatic event is thought to contribute to the indelibility of fear memory. Given a well-established role of hippocampus for memory reactivation, hippocampus is likely involved in consolidation process of fear memory

The dopamine (DA) system has a profound impact on reward-motivated behavior and is critically involved in neurodevelopmental disorders, such as autism spectrum disorder (ASD). Although DA defects are found in autistic patients, it is not well defined how the DA pathways are altered in ASD and whether DA can be utilized as a potential therapeutic agent for ASD. To this end, we employed a phenotypic

Autism Spectrum Disorders (ASD) are characterised by deficits in social interactions and repetitive behaviours. Multiple ASD-associated mutations have been identified in the Shank family of proteins that play a critical role in the structure and plasticity of glutamatergic synapses, leading to impaired synapse function and the presentation of ASD-associated behavioural deficits in mice. Shank proteins

Leptin, secreted by peripheral adipocytes, binds the leptin receptor (Lepr) in the hypothalamus, thereby contributing to the regulation of satiety and body weight. Lepr is expressed in the embryonic brain as early as embryonic day 12.5. However, the function of Lepr in neural precursor cells in the brain has not been resolved. To address this issue, we crossed the Leprflox/flox mice with each of Shh-Cre

Parkinson’s disease (PD) is characterized by the formation of toxic, fibrillar form alpha-synuclein (α-Syn) protein aggregates in dopaminergic neurons. Accumulating evidence has shown a multifactorial interplay between the intracellular calcium elevation and α-Syn dynamics. However, whether membrane depolarization regulates toxic α-Syn aggregates remains unclear. To understand this better, we used

The insular cortex (IC) is the primary gustatory cortex, and it is a critical structure for encoding and retrieving the conditioned taste aversion (CTA) memory. In the CTA, consumption of an appetitive tastant is associated with aversive experience such as visceral malaise, which results in avoidance of consuming a learned tastant. Previously, we showed that levels of the cyclic-AMP-response-element-binding

Temporomandibular disorder (TMD) is commonly comorbid with fibromyalgia syndrome (FMS). The incidence of these pain conditions is prevalent in women and prone to mental stress. Chronic pain symptoms in patients with FMS and myofascial TMD (mTMD) are severe and debilitating. In the present study, we developed a new animal model to mimic the comorbidity of TMD and FMS. In ovariectomized female rats,

Proper dendrite morphogenesis and neuronal migration are crucial for cerebral cortex development and neural circuit formation. In this study, we sought to determine if the histone deacetylase HDAC6 plays a role in dendrite development and neuronal migration of pyramidal neurons during cerebral cortex development. It was observed that knockdown of HDAC6 leads to defective dendrite morphogenesis and

The highly conserved and ubiquitously expressed transcription factor Yin Yang 1 (Yy1), was named after its dual functions of both activating and repressing gene transcription. Yy1 plays complex roles in various fundamental biological processes such as the cell cycle progression, cell proliferation, survival, and differentiation. Patients with dominant Yy1 mutations suffer from central nervous system

Brain injury causes astrocytes to become reactive (astrogliosis). In this study, we compared astrogliosis in acutely injured cortex and striatum of adult FVB/N mice induced by stereotaxic injection of ATP, a component of danger-associated molecular patterns (DAMPs). Interestingly, MR analysis showed that same amount of ATP induced smaller damage in the cortex than in the striatum. However, in histological

Parkinson’s disease (PD) is the second most common neurodegenerative disease, and mild cognitive impairment (MCI) is a well-established risk factor for the development of dementia in PD. A growing body of evidence suggests that low expression of glucocerebrosidase (GBA) promotes the transmission of α-synuclein (α-Syn) interpolymers and the progression of PD. However, how GBA mutations affect the pathogenesis

The defining features of a neuron are its functional and anatomical connections with thousands of other neurons in the brain. Together, these neurons form functional networks that direct animal behavior. Current approaches that allow the interrogation of specific populations of neurons and neural circuits rely heavily on targeting their gene expression profiles or connectivity. However, these approaches

Cellular and synaptic mechanisms underlying how chronic pain induces maladaptive alterations to local circuits in the medial prefrontal cortex (mPFC), while emerging, remain unresolved. Consistent evidence shows that chronic pain attenuates activity in the prelimbic (PL) cortex, a mPFC subregion. This reduced activity is thought to be driven by increased inhibitory tone within PL circuits. Enhanced

The serotonin (5-HT) system is the target of multiple anxiolytics, including Buspirone, which is a partial agonist of the serotonin 1A receptor (5-HT1A). Similarly, ligands of the serotonin 2A receptor (5-HT2A) were shown to alter anxiety level. The 5-HT1A and 2A receptors are widely expressed across the brain, but the target region(s) underlying the influence of those receptors on anxiety remain unknown

In many mammalian species, the production of new neurons in the hippocampal dentate gyrus continues throughout life. Previous studies using rodents suggest that adult-born neurons are involved in memory and cognition tasks and mood regulation. Interferon-alpha (IFNα), a proinflammatory cytokine used for the treatment of chronic viral hepatitis and malignancies, frequently causes depressive symptoms

Effective treatment of high-impact pain patients is one of the major stated goals of the National Pain Strategy in the United States. Identification of new targets and mechanisms underlying neuropathic pain will be critical in developing new target-specific medications for better neuropathic pain management. We recently discovered that peripheral nerve injury-induced upregulation of an axonal guidance

The present review systematically summarized existing publications regarding the genetic associations between voltage-gated calcium channels (VGCCs) and autism spectrum disorder (ASD). A comprehensive literature search was conducted to gather pertinent studies in three online databases. Two authors independently screened the included records based on the selection criteria. Discrepancies in each step

Low-voltage-activated Cav3 calcium channels (T-type) play an essential role in the functioning of the nervous system where they support oscillatory activities that relie on several channel molecular determinants that shape their unique gating properties. In a previous study, we documented the important role of the carboxy proximal region in the functioning of Cav3.3 channels. Here, we explore the ability

Members of the leukocyte common antigen-related receptor protein tyrosine phosphatase (LAR-RPTP) family, comprising PTPσ, PTPδ and LAR, are key hubs for presynaptic assembly and differentiation in vertebrate neurons. However, roles of individual LAR-RPTP members have not been investigated using member-specific conditional knockout mice. Here, we show that loss of PTPδ had no overt effect on synapse

Viral infection during pregnancy has been suggested to increase the probability of autism spectrum disorder (ASD) in offspring via the phenomenon of maternal immune activation (MIA). This has been modeled in rodents. Maternal T helper 17 cells and the effector cytokine, interleukin 17A (IL-17A), play a central role in MIA-induced behavioral abnormalities and cortical dysgenesis, termed cortical patch

Accumulating evidence implicates dysregulation of hippocampal synaptic plasticity in the pathophysiology of depression. However, the effects of ketamine on synaptic plasticity and their contribution to its mechanism of action as an antidepressant, are still unclear. We investigated ketamine’s effects on in vivo dorsal hippocampal (dHPC) synaptic plasticity and their role in mediating aspects of antidepressant

Postpartum depression (PPD) is a serious psychiatric disorder, affecting not only the childbearing women but also the health of their offsprings. The brain-derived neurotrophic factor (Bdnf) gene is an important target gene for the study of depression and antidepressant therapy. FoxO1, belonging to the FoxO subfamily is involved in the development of major depressive disorders. However, the role of

Drp1 is widely expressed in the mouse central nervous system and plays a role in inducing the mitochondrial fission process. Many diseases are associated with Drp1 and mitochondria. However, since the exact distribution of Drp1 has not been specifically observed, it is difficult to determine the impact of anti-Drp1 molecules on the human body. Clarifying the specific Drp1 distribution could be a good

Neurodegenerative diseases are characterized by progressive cognitive decline and the loss of neurons in the central nervous system; many are also characterized by abnormal aggregation of misfolded proteins. Ubiquitin (Ub) is a eukaryotic protein that plays pivotal roles in protein degradation and cellular signaling. Ubiquitinated aggregates are observed in neurodegenerative diseases; this ultimately

Microglia are macrophages resident in the central nervous system. C-X3-C motif chemokine receptor 1 (CX3CR1) is a Gαi-coupled seven-transmembrane protein exclusively expressed in the mononuclear phagocyte system including microglia, as well as intestinal and kidney macrophages. Cx3cr1CreERT2 mice express Cre recombinase in a tamoxifen-inducible manner and have been widely used to delete target genes

The Disrupted in schizophrenia 1 (DISC1) gene encodes a scaffolding protein that is involved in many neural functions such as neurogenesis, neural differentiation, embryonic neuron migration and neurotransmitter signalling. DISC1 was originally implicated in schizophrenia in a single family with a drastic mutation, a chromosomal translocation severing the mid-point of the gene (aa 598). Some common

Propionic acid (PPA) is a short-chain fatty acid that is an important mediator of cellular metabolism. It is also a by-product of human gut enterobacteria and a common food preservative. A recent study found that rats administered with PPA showed autistic-like behaviors like restricted interest, impaired social behavior, and impaired reversal in a T-maze task. This study aimed to identify a link between

Genetic and epigenetic factors contribute to the development of the spinal cord. Failure in correct exertion of the developmental programs, including neurulation, neural tube closure and neurogenesis of the diverse spinal cord neuronal subtypes results in defects of variable severity. We here report on the histone methyltransferase Disruptor of Telomeric 1 Like (DOT1L), which mediates histone H3 lysine

Clozapine is thought to induce obsessive compulsive symptoms (OCS) in schizophrenic patients. However, because OCS are often comorbid with schizophrenia regardless of clozapine treatment, it remains unclear whether clozapine can generate OCS de novo. Thus, it has been difficult to establish a causal link between clozapine and OCS in human studies. To address this question, we asked whether chronic