LAMA2-related congenital muscular dystrophy (CMD; LAMA2-MD), also referred to as merosin deficient CMD (MDC1A), is a severe neonatal onset muscle disease caused by recessive mutations in the LAMA2 gene. LAMA2 encodes laminin α2, a subunit of the extracellular matrix (ECM) oligomer laminin 211. There are currently no treatments for MDC1A, and there is an incomplete understanding of disease pathogenesis

Phytocannabinoids are psychotropic substances ofcannabis with the ability to bind endocannabinoid (eCB) receptors that regulate synaptic activity in the central nervous system (CNS). Synthetic cannabinoids (SCs) are synthetic analogs of Δ9-tetrahydrocannabinol (Δ9-THC), the psychotropic compound of cannabis, acting as agonists of eCB receptor CB1. SC is an easily available and popular alternative to

Techniques that allow the manipulation of specific neural circuits have greatly increased in the past few years. DREADDs (Designer receptors exclusively activated by designer drugs) provide an elegant way to manipulate individual brain structures and/or neural circuits, including neuromodulatory pathways. Considerable efforts have been made to increase cell-type specificity of DREADD expression while

Background: In Alzheimer’s disease (AD) neuronal degeneration is associated with gliosis and infiltration of peripheral blood mononuclear cells (PBMCs), which participate in neuroinflammation. Defects at the blood-brain barrier (BBB) facilitate PBMCs migration towards the central nervous system (CNS) and in particular CD4+ T cells have been found in areas severely affected in AD. However, the role

Oxidative stress (OS) plays a critical role in the pathophysiology of several brain-related disorders, including neurodegenerative diseases and ischemic stroke, which are the major causes of dementia. The Nrf2-ARE (nuclear factor erythroid 2-related factor 2/antioxidant responsive element antioxidant) system, the primary cellular defense against OS, plays an essential role in neuroprotection by regulating

Protocadherins (Pcdhs) are cell adhesion molecules that belong to the cadherin superfamily, and are subdivided into clustered (cPcdhs) and non-clustered Pcdhs (ncPcdhs) in vertebrates. In this review, we summarize their discovery, expression mechanisms, and roles in neuronal development and cancer, thereby highlighting the context-dependent nature of their actions. We furthermore provide an extensive

Background: Altered white matter connectivity, as evidenced by pervasive microstructural changes in myelination and axonal integrity in neuroimaging studies, has been implicated in the development of autism spectrum disorder (ASD) and related neurodevelopmental conditions such as schizophrenia. Despite an increasing appreciation that such white matter disconnectivity is linked to social behavior deficits

Multiple sclerosis (MS) is an inflammatory autoimmune disease affecting the central nervous system (CNS) that currently does not have any effective treatment. Experimental autoimmune encephalomyelitis (EAE) is often employed as a model to mimic the clinical manifestations of MS, mainly CNS demyelination. Coagulation is known to participate in crosstalk with inflammation and autoimmunity. We herein

Neurons extend long processes known as axons and dendrites, through which they communicate with each other. The neuronal circuits formed by the axons and dendrites are the structural basis of higher brain functions. The formation and maintenance of these processes are essential for physiological brain activities. Membrane components, both lipids, and proteins, that are required for process formation

M/Kv7 potassium channels play a key role in regulation of neuronal excitability. Modulation of neuronal excitability of primary sensory neurons determines the itch sensation induced by a variety of itch-causing substances including chloroquine (CQ). In the present study, we demonstrate that suppression of M/Kv7 channel activity contributes to generation of itch in mice. CQ enhances excitability of

Introduction Ketamine, which is widely used in anesthesia, can induce cortical neurotoxicity in patients. This study aims to investigate the effects of long non-coding RNA LINC00641 on the ketamine-induced neural injury. Materials and Methods In this study, rat pheochromocytoma cells (PC12 cells) were used as a cell model and Sprague–Dawley postnatal day 7 rats were used for experiments in vivo. Ketamine-induced

Parkinson’s disease (PD) is a common neurodegenerative disease in the elderly with a pathogenesis that remains unclear. We aimed to explore its pathogenesis through plasma integrated metabolomics and proteomics analysis. The clinical data of consecutively recruited PD patients and healthy controls were assessed. Fasting plasma samples were obtained and analyzed using metabolomics and proteomics methods

Aim: Traumatic brain injury (TBI) is a leading cause of mortality/morbidity and is associated with chronic neuroinflammation. Melanocortin receptor agonists including adrenocorticotropic hormone (ACTH) ameliorate inflammation and provide a novel therapeutic approach. We examined the effect of long-acting cosyntropin (CoSyn), a synthetic ACTH analog, on the early inflammatory response and functional

Reducing the extent of secondary degeneration following spinal cord injury (SCI) is necessary to preserve function, but treatment options have thus far been limited. A combination of the ion channel inhibitors Lomerizine (Lom), YM872 and oxATP, to inhibit voltage-gated Ca2+ channels, Ca2+ permeable AMPA receptors, and purinergic P2X7 receptors respectively, effectively limits secondary consequences

Argyrophilic grain disease (AGD) is a common 4R-tauopathy, causing or contributing to cognitive impairment in the elderly. AGD is characterized neuropathologically by pre-tangles in neurons, dendritic swellings called grains, threads, thorn-shaped astrocytes, and coiled bodies in oligodendrocytes in the limbic system. AGD has a characteristic pattern progressively involving the entorhinal cortex, amygdala

Amongst other approaches, adipose-derived stromal cells (ASCs) have recently been tested with respect to their regenerative capacity for treatment of neuromuscular disorders. While beneficial effects of ASCs on muscle recovery were observed previously, their impact on regeneration of neuromuscular junctions (NMJs) is unclear. Here, we used a murine glycerol damage model to study disruption and regeneration

Transthyretin variant amyloidosis (ATTRv) is a rare autosomal dominant disease characterized by the accumulation of amyloid in many organs, mostly causing a sensory-motor neuropathy, cardiomyopathy, and dysautonomia. The aim of the study was to report microRNAs (miRNAs) expression profile identified in the blood of ATTRv patients. Ten ATTRv patients, 10 asymptomatic carriers of transthyretin variant

Acute central nervous system (CNS) disease is very common and with high mortality. Many basic studies have confirmed the molecular mechanism of early brain injury (EBI) after acute CNS disease. Neuron death and dysfunction are important reasons for the neurological dysfunction in patients with acute CNS disease. Ferroptosis is a nonapoptotic form of cell death, the classical characteristic of which

Shortage of oxygen and nutrients in the brain induces the release of glutamate and ATP that can cause excitotoxicity and contribute to neuronal and glial damage. Our understanding of the mechanisms of ATP release and toxicity in cerebrovascular diseases is incomplete. This review aims at summarizing current knowledge about the participation of key elements in the ATP-mediated deleterious effects in

Parkinson’s disease (PD) is a neurodegenerative disease that affects substantia nigra dopamine neurons. Many studies have documented the role of oxidative stress and angiogenesis in the pathogenesis of PD. Metformin (MTF) is an antidiabetic medication and AMP-activated protein kinase (AMPK) regulator that has shown antioxidant and antiangiogenic properties in many disorders. The aim of this study is

The endocannabinoid system (ECS) acts as a negative feedback mechanism to suppress synaptic transmission and plays a major role in a diverse range of brain functions including, for example, the regulation of mood, energy balance, and learning and memory. The function and dysfunction of the ECS are strongly implicated in multiple psychiatric, neurological, and neurodegenerative diseases. Cannabinoid

The neuromuscular junctions (NMJs) connect muscle fibers with motor neurons and enable the coordinated contraction of skeletal muscles. The dystrophin-associated glycoprotein complex (DGC) is an essential component of the postsynaptic machinery of the NMJ and is important for the maintenance of NMJ structural integrity. To identify novel proteins that are important for NMJ organization, we performed

The modification of methyltransferase-like (METTL) enzymes plays important roles in various cellular responses by regulating microRNA expression. However, how m6A modification is involved in stress granule (SG) formation in the early stage of acute ischemic stroke by affecting the biogenesis processing of microRNAs remains unclear. Here, we established a middle cerebral artery occlusion (MCAO) model

Background: Hypothermia attenuates microglial activation and exerts a potential neuroprotective effect against cerebral ischemic-reperfusion (I/R) injury. However, the underlying mechanism remains to be elucidated. In this in vitro study, a model of oxygen-glucose deprivation, followed by recovery (OGD/R), was used to investigate whether hypothermia exerts anti-inflammatory and anti-apoptosis properties

The role of ion channels in neurons and muscles has been well characterized. However, recent work has demonstrated both the presence and necessity of ion channels in diverse cell types for morphological development. For example, mutations that disrupt ion channels give rise to abnormal structural development in species of flies, frogs, fish, mice, and humans. Furthermore, medications and recreational

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease that targets motor neurons (MNs) in the brain and spinal cord. It leads to gradual loss of motor signals to muscles leading to atrophy and weakness. Most patients do not survive for more than 3–5 years after disease onset. Current ALS treatments provide only a small delay of disease progression. Therefore, it is of utmost

Physical or psychological stress can cause an immunologic imbalance that disturbs the central nervous system followed by neuroinflammation. The association between inflammation and depression has been widely studied in recent years, though the molecular mechanism is still largely unknown. Thus, targeting the signaling pathways that link stress to neuroinflammation might be a useful strategy against

Epileptogenesis is a common consequence of brain insults, however, the prevention or delay of the epileptogenic process remains an important unmet medical challenge. Overexpression of glycine transporter 1 (GlyT1) is proposed as a pathological hallmark in the hippocampus of patients with temporal lobe epilepsy (TLE), and we previously demonstrated in rodent epilepsy models that augmentation of glycine

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by a progressive cognitive decline associated with global brain damage. Initially, intracellular paired helical filaments composed by hyperphosphorylated tau and extracellular deposits of amyloid-β (Aβ) were postulated as the causing factors of the synaptic dysfunction, neuroinflammation, oxidative stress, and neuronal

This review focuses on the purinergic ionotropic receptor P2X7 (P2X7R) as a potential target for developing drugs that delay the onset and/or disease progression in patients with amyotrophic lateral sclerosis (ALS). Description of clinical and genetic ALS features is followed by an analysis of advantages and drawbacks of transgenic mouse models of disease based on mutations in a bunch of proteins,

Neuropathic pain (NP) is caused by primary or secondary impairment of the peripheral or central nervous systems. Its etiology is complex and involves abnormal patterns of gene expression and pathway activation. Using bioinformatics analysis, we aimed to identify NP-associated changes in genes and pathways in L4 and L5 dorsal root ganglia (DRG) in a rat model of NP induced by chronic compression of

The RNA-binding protein RBFOX1 is an important regulator of neuron development and neuronal excitability. Rbfox1 is a dosage-sensitive gene and in both mice and humans, decreased expression of Rbfox1 has been linked to neurodevelopmental disorders. Alternative promoters drive expression of Rbfox1 transcript isoforms that encode an identical protein. The tissue- and developmental stage-specific expression

Nowadays, pain represents one of the most important societal burdens. Current treatments are, however, too often ineffective and/or accompanied by debilitating unwanted effects for patients dealing with chronic pain. Indeed, the prototypical opioid morphine, as many other strong analgesics, shows harmful unwanted effects including respiratory depression and constipation, and also produces tolerance

Motoneurons axotomized by peripheral nerve injuries experience profound changes in their synaptic inputs that are associated with a neuroinflammatory response that includes local microglia and astrocytes. This reaction is conserved across different types of motoneurons, injuries, and species, but also displays many unique features in each particular case. These reactions have been amply studied, but

Progressive functional deterioration and loss of neurons underlies neurological diseases and constitutes an important cause of disability and death worldwide. The causes of various types of neurological diseases often share several critical nerve-related cellular mechanisms and pathological features, particularly the neuroinflammatory response in the nervous system. A rapidly growing body of evidence

Altered serotonin (5-HT) signaling is associated with multiple brain disorders, including major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and autism spectrum disorder (ASD). The presynaptic, high-affinity 5-HT transporter (SERT) tightly regulates 5-HT clearance after release from serotonergic neurons in the brain and enteric nervous systems, among other sites. Accumulating evidence

Changes in excitation and inhibition are associated with the pathobiology of neurodevelopmental disorders of intellectual disability and autism and are widely described in Fragile X syndrome (FXS). In the prefrontal cortex (PFC), essential for cognitive processing, excitatory connectivity and plasticity are found altered in the FXS mouse model, however, little is known about the state of inhibition

Myasthenia gravis (MG) is a disease of the postsynaptic neuromuscular junction (NMJ) where nicotinic acetylcholine (ACh) receptors (AChRs) are targeted by autoantibodies. Search for other pathogenic antigens has detected the antibodies against muscle-specific tyrosine kinase (MuSK) and low-density lipoprotein-related protein 4 (Lrp4), both causing pre- and post-synaptic impairments. Agrin is also suspected

Opioid analgesics represent a critical treatment for chronic pain in the analgesic ladder of the World Health Organization. However, their use can result in a number of unwanted side-effects including incomplete efficacy, constipation, physical dependence, and overdose liability. Cannabinoids enhance the pain-relieving effects of opioids in preclinical studies and dampen unwanted side-effects resulting

Brain metabolic DNA (BMD) is continuously synthesized by reverse transcription in presynaptic synaptosomes and astroglia, and is partly transferred to nuclei after acquiring the double stranded configuration. Synthesis and turnover of BMD are markedly dependent on brain activity, as shown by circadian oscillations, environmental enrichment and impoverishment, and a variety of learning protocols. In

In the mature cochlea, each inner hair cell (IHC) is innervated by multiple spiral ganglion neurons of type I (SGNI). SGNIs are morphologically and electro-physiologically diverse. Also, they differ in their susceptibility to noise insult. However, the molecular underpinnings of their identity and physiological differences remain poorly understood. In this study, we developed a novel triple transgenic

Background Tardive dyskinesia (TD) is a common side effect of antipsychotic treatment. This movement disorder consists of orofacial and limb-truncal components. The present study is aimed at investigating the role of serotonin receptors (HTR) in modulating tardive dyskinesia by genotyping patients with schizophrenia. Methods A set of 29 SNPs of genes of serotonin receptors HTR1A, HTR1B, HTR2A, HTR2C

Ion channels are expressed throughout nervous system development. The type and diversity of conductances and gating mechanisms vary at different developmental stages and with the progressive maturational status of neural cells. The variety of ion channels allows for distinct signaling mechanisms in developing neural cells that in turn regulate the needed cellular processes taking place during each

In utero electroporation (IUE) is a powerful tool for testing the role of genes in neuronal migration and function, but this technique suffers from high degrees of variability. Such variability can result from inconsistent surgery, developmental gradients along both rostral-caudal and medial-lateral axes, differences within littermates and from one litter to another. Comparisons between control and

Glycogen synthase kinase-3 (GSK-3) dysregulation has been implicated in nigral dopaminergic neurodegeneration, one of the main pathological features of Parkinson’s disease (PD). The two isoforms, GSK-3α and GSK-3β, have both been suggested to play a detrimental role in neuronal death. To date, several studies have focused on the role of GSK-3β on PD pathogenesis, while the role of GSK-3α has been largely

Social recognition is fundamental for social decision making and the establishment of long-lasting affiliative behaviors in behaviorally complex social groups. It is a critical step in establishing a selective preference for a social partner or group member. C57BL/6J lab mice do not form monogamous relationships, and typically do not show prolonged social preferences for familiar mice. The CA2 hippocampal

Merosin deficient Congenital Muscular Dystrophy (MDC1A), or LAMA2-related muscular dystrophy (LAMA2-RD), is a recessive disorder resulting from mutations in the LAMA2 gene, encoding for the alpha-2 chain of laminin-211. The disease is predominantly characterized by progressive muscular dystrophy affecting patient motor function and reducing life expectancy. However, LAMA2-RD also comprises a devel

Brain derived exosomes (BDEs) are extracellular nanovesicles that are collectively released by all cell lineages of the central nervous system and contain cargo from their original cells. They are emerging as key mediators of communication and waste management among neurons, glial cells and connective tissue during both physiological and pathological conditions in the brain. We review the rapidly growing

Genetic analyses of patients with amyotrophic lateral sclerosis (ALS) have revealed a strong association between mutations in genes encoding many RNA-binding proteins (RBPs), including TARDBP, FUS, hnRNPA1, hnRNPA2B1, MATR3, ATXN2, TAF15, TIA-1, and EWSR1, and disease onset/progression. RBPs are a group of evolutionally conserved proteins that participate in multiple steps of RNA metabolism, including

The research on laminin α2 chain-deficient congenital muscular dystrophy (LAMA2-CMD) advanced rapidly in the last few decades, largely due to availability of good mouse models for the disease and a strong interest in preclinical studies from scientists all over the world. These mouse models continue to provide a solid platform for understanding the LAMA2-CMD pathology. In addition, they enable researchers

Though it is well known that chronic infections of Toxoplasma gondii (T. gondii) can induce mental and behavioral disorders in the host, little is known about the role of long non-coding RNAs (lncRNAs) in this pathological process. In this study, we employed an advanced lncRNAs and mRNAs integration chip (Affymetrix HTA 2.0) to detect the expression of both lncRNAs and mRNAs in T. gondii Chinese 1

The striatum, the main input structure of the basal ganglia, is critical for action selection and adaptive motor control. To understand the neuronal mechanisms underlying these functions, an analysis of microcircuits that compose the striatum is necessary. Among these, cholinergic interneurons (ChIs) provide intrinsic striatal innervation whose dysfunction is implicated in neuropsychiatric diseases

The superficial dorsal horn (SDH, LI-II) of the spinal cord receives and processes multimodal sensory information from skin, muscle, joints, and viscera then relay it to the brain. Neurons within the SDH fall into two broad categories, projection neurons and interneurons. The later can be further subdivided into excitatory and inhibitory types. Traditionally, interneurons within the SDH have been divided

The visualization of multiple gene expressions in well-preserved tissues is crucial for the elucidation of physiological and pathological processes. In situ hybridization chain reaction (HCR) is a method to visualize specific mRNAs in diverse organisms by applying a HCR that is an isothermal enzyme-free nucleotide polymerization method using hairpin DNAs. Although in situ HCR is a versatile method

The brain is complex and heterogeneous. Even though numerous independent studies indicate cortical hyperexcitability as a potential contributor to amyotrophic lateral sclerosis (ALS) pathology, the mechanisms that are responsible for upper motor neuron (UMN) vulnerability remain elusive. To reveal the electrophysiological determinants of corticospinal motor neuron (CSMN, a.k.a UMN in mice) vulnerability

The most evident phenotype of degenerative motoneuron disease is the loss of motor function which accompanies motoneuron death. In both amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), it is now clear that dysfunction is not restricted to motoneurons but is manifest in the spinal circuits in which motoneurons are embedded. As mounting evidence shows that motoneurons possess more

Lysophospholipids (LPLs) are bioactive signaling lipids that are generated from phospholipase-mediated hydrolyzation of membrane phospholipids (PLs) and sphingolipids (SLs). Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are two of the best-characterized LPLs which mediate a variety of cellular physiological responses via specific G-protein coupled receptor (GPCR) mediated signaling

Neurodegenerative diseases (NDDs) are a group of diseases caused by chronic and progressive degeneration of neural tissue. The main pathological manifestations are neuronal degeneration and loss in the brain and/or spinal cord. Common NDDs include Alzheimer disease (AD), Parkinson disease (PD), Huntington disease (HD), and amyotrophic lateral sclerosis (ALS). The complicated pathological characteristics

Increasing evidence from animal and human studies indicate that exposure to nicotine during development, separated from the effects of smoking tobacco, can contribute to dysregulation of brain development including behavioral deficits. An RNAseq study of human fetal cerebral cortex demonstrated that 9 out of 16 genes for human nicotinic acetylcholine (ACh) receptor subunits are selectively expressed

Muscle stem cells (MuSCs), known as satellite cells (SCs) have an incredible ability to regenerate, which enables the maintenance and growth of muscle tissue. In response to damaging stimuli, SCs are activated, proliferate, differentiate, and fuse to repair or generate a new muscle fiber. However, dystrophic muscles are characterized by poor muscle regeneration along with chronic inflammation and fibrosis