p38 Inhibitor Protects Mitochondrial Dysfunction by Induction of DJ-1 Mitochondrial Translocation After Subarachnoid Hemorrhage
This study suggested that overexpression of p38 induced the accumulation of mitochondrial dysfunction partly due to abnormal activation of autophagy, which largely relied on DJ-1 mitochondrial translocation. (Source: Journal of Molecular Neuroscience)
Source: Journal of Molecular Neuroscience - September 21, 2018 Category: Neuroscience Source Type: research

PAXX Participates in Base Excision Repair via Interacting with Pol β and Contributes to TMZ Resistance in Glioma Cells
In conclusion, the PAXX contributes to a variety of DNA repair pathways and TMZ resistance. Therefore, inhibition of PAXX may provide a promising way to overcome TMZ resistance and improve TMZ therapeutic effects in glioma treatment. (Source: Journal of Molecular Neuroscience)
Source: Journal of Molecular Neuroscience - September 20, 2018 Category: Neuroscience Source Type: research

Genetic Variation of the Kalirin Gene is Associated with ICAS in the Chinese Population
AbstractIntracranial atherosclerotic stenosis (ICAS) is one of the most common causes of ischemic stroke (IS), especially in recurrent patients. Several studies have demonstrated an intimate association between the genetic mutation of theKALRN gene and IS. The main aim of this study was to clarify the relationship between three single nucleotide polymorphisms (SNPs) ofKALRN and ICAS in a northern Chinese population and further explore the underlining mechanism. The relationship between each SNP and ICAS and the related components were examined in five models (co-dominant, dominant, recessive, heterozygous, and additive). M...
Source: Journal of Molecular Neuroscience - September 19, 2018 Category: Neuroscience Source Type: research

Carob ( Ceratonia siliqua L.) Prevents Short-Term Memory Deficit Induced by Chronic Stress in Rats
AbstractLong-term exposure to stressful conditions could impair the normal brain structure and function, specifically the hippocampus-dependent memory. This impairment could be attributed to a decrease in brain-derived neurotrophic factor (BDNF) levels during chronic stress. Knowing that carob [Ceratonia siliqua L. (Fabaceae)] is rich in a wide variety of polyphenols with a high antioxidant value, we hypothesized that the methanolic carob extract (C. siliqua) pods will prevent stress-induced memory impairment. Hence, the methanolic extract of carob pods was investigated for its ability to enhance learning and memory as wel...
Source: Journal of Molecular Neuroscience - September 14, 2018 Category: Neuroscience Source Type: research

Correction to: Implication of OPRM1 A118G Polymorphism in Opioids Addicts in Pakistan: In vitro and In silico Analysis
The original version of this article is missing the Acknowledgments section. (Source: Journal of Molecular Neuroscience)
Source: Journal of Molecular Neuroscience - September 14, 2018 Category: Neuroscience Source Type: research

Expression of ASIC3 in the Trigeminal Nucleus Caudalis Plays a Role in a Rat Model of Recurrent Migraine
In this study, we established a rat model of RM through repeated administration of inflammatory soup (IS) onto the dura. Then, we tested the mechanical pain thresholds of the face and hindpaws by von Frey filaments. qRT-PCR, Western blot and immunofluorescence labelling were used to detect the expression and localization of ASIC3 in the trigeminal nucleus caudalis (TNC). The protein levels of calcitonin gene-related peptide (CGRP), its receptor component receptor activity modifying protein 1 (RAMP1) and c-Fos were analysed following treatment with the ASIC3 inhibitor APETx2 and activator 2-guanidine-4-methylquinazoline (GM...
Source: Journal of Molecular Neuroscience - September 12, 2018 Category: Neuroscience Source Type: research

Neuregulin-1 β Plays a Neuroprotective Role by Inhibiting the Cdk5 Signaling Pathway after Cerebral Ischemia-Reperfusion Injury in Rats
This study investigated the effects of neuregulin-1 β (NRG1β) after middle cerebral artery occlusion/reperfusion (MCAO/R) in rats to evaluate whether they occur via the cyclin-dependent kinase (Cdk)5 signaling pathway. One hundred adult male Wistar rats were randomly divided into sham, MCAO/R, treatment (NRG1β), inhibitor (roscovitine; Ros), and i nhibitor + treatment (Ros + NRG1β) groups. The MCAO/R model was established using the intraluminal thread method. The neurobehavioral function was evaluated by the modified neurological severity score (mNSS). The cerebral infarction volume (CIV) ...
Source: Journal of Molecular Neuroscience - September 11, 2018 Category: Neuroscience Source Type: research

HIF-1 α/Beclin1-Mediated Autophagy Is Involved in Neuroprotection Induced by Hypoxic Preconditioning
AbstractHypoxic preconditioning (HPC) exerts a protective effect against hypoxic/ischemic brain injury, and one mechanism explaining this effect may involve the upregulation of hypoxia-inducible factor-1 (HIF-1). Autophagy, an endogenous protective mechanism against hypoxic/ischemic injury, is correlated with the activation of the HIF-1 α/Beclin1 signaling pathway. Based on previous studies, we hypothesize that the protective role of HPC may involve autophagy occurring via activation of the HIF-1α/Beclin1 signaling pathway. To test this hypothesis, we evaluated the effects of HPC on oxygen-glucose deprivation/r...
Source: Journal of Molecular Neuroscience - September 10, 2018 Category: Neuroscience Source Type: research

A Novel SYNJ1 Mutation in a Tunisian Family with Juvenile Parkinson ’s Disease Associated with Epilepsy
In this study, we report two siblings, from a consanguineous Tunisian family, presenting juvenile PD. Both siblings developed mild Parkinsonism at 16 and 21 years old respectively. On e patient had generalized tonic-clonic seizures since the age of 7 years. There was no evidence of sleep or autonomic dysfunctions and psychiatric disorders in both cases, but they developed a moderate cognitive impairment. They kept a good respond to low doses of levodopa treatment with no dyskine sia or motor fluctuations. We designed an NGS-based screening of 22 currently most prevalent parkinsonism-associated genes. Genetic stud...
Source: Journal of Molecular Neuroscience - September 5, 2018 Category: Neuroscience Source Type: research

Co-Administration of Progesterone and Melatonin Attenuates Ischemia-Induced Hippocampal Damage in Rats
AbstractStroke is the second leading reason for death worldwide and is one of the fundamental causes of long-term disabilities. The aim of this investigation was to assess the impact of combined administration progesterone (PROG) and melatonin (MEL) on stroke complications. Male Wistar rats (9 –10 weeks) weighing 250–300 g were used as a part of this examination. They were randomly separated into eight groups (nine rats for every group). Common carotid arteries on the two sides clamped (BCCAO model) with non-traumatic clips for 20 min. At that point, the rats were treated with 8 m g/kg PROG,...
Source: Journal of Molecular Neuroscience - September 4, 2018 Category: Neuroscience Source Type: research

Combined Gene Therapy to Reduce the Neuronal Damage in the Mouse Model of Focal Ischemic Injury
AbstractResearch into stroke is driven by frustration over the limited available therapeutics. Targeting a single aspect of this multifactorial disease contributes to the therapeutic boundaries. To overcome this, we devised a novel multifactorial-cocktail treatment, using lentiviruses encoding excitatory amino acid transporter 2 (EAAT2(, glutamate dehydrogenase 2 (GDH2), and nuclear factor E2-related factor 2 (Nrf2) genes, that acts synergistically to address the effected excito-oxidative axis. Here, we used the vasoconstrictor endothelin-1 (ET-1) to induce focal ischemic injury in mice by direct injection into the striatu...
Source: Journal of Molecular Neuroscience - September 3, 2018 Category: Neuroscience Source Type: research

Ferroptosis, a Recent Defined Form of Critical Cell Death in Neurological Disorders
AbstractFerroptosis is a recently defined form of cell death with the involvement of iron and reactive oxygen species (ROS), which is distinct from apoptosis, autophagy and other forms of cell death. Emerging evidence suggested that iron accumulation and lipid peroxidation can be discovered in various neurological diseases, accompanied with reduction of glutathione (GSH) and glutathione peroxidase 4 (GPX4). In addition, ferroptotic inhibitors have been shown to protect neurons, and recover the cognitive function in disease animal models. This review summarizes the mechanisms underlying ferroptosis and reviews the contribut...
Source: Journal of Molecular Neuroscience - August 25, 2018 Category: Neuroscience Source Type: research

Bisphenol S Triggers the Migration and Invasion of Pheochromocytoma PC12 Cells via Estrogen-Related Receptor α
AbstractPheochromocytoma (PCC) is a tumor of the adrenal medulla for which surgical resection is the only therapy approach. Risk factors responsible for the tumorigenesis and progression of PCC are not well illustrated. Our present study revealed that an industrial chemical, bisphenol S (BPS), can promote the migration and invasion of PCC PC12 cells, which was evidenced by the upregulation of fibronectin (FN) and matrix metalloproteinases (MMP-2 and MMP-9). The inhibitor of estrogen-related receptor α (ERRα), while not estrogen receptor α/β (ERα/β) or G protein-coupled estrogen receptor (G...
Source: Journal of Molecular Neuroscience - August 23, 2018 Category: Neuroscience Source Type: research

Nrf2 Signaling in Sodium Azide-Treated Oligodendrocytes Restores Mitochondrial Functions
AbstractMitochondrial dysfunctions mark a critical step in many central nervous system (CNS) pathologies, including multiple sclerosis (MS). Such dysfunctions lead to depolarization of mitochondrial membranes and imbalanced redox homeostasis. In this context, reactive oxygen species (ROS) are potentially deleterious but can also act as an important signaling step for cellular maintenance. The transcription factor nuclear  factor (erythroid-derived 2)-like 2 (Nrf2), the key regulator in the cellular oxidative stress-response, induces a battery of genes involved in repair and regeneration. Here, we investigated the...
Source: Journal of Molecular Neuroscience - August 23, 2018 Category: Neuroscience Source Type: research

Potential of Extracellular Vesicles in Neurodegenerative Diseases: Diagnostic and Therapeutic Indications
AbstractExtracellular vesicles (EVs) are membrane-bound vesicles, including exosomes and microvesicles. EVs are nanometer sized, found in physiological fluids such as urine, blood, cerebro-spinal fluid (CSF), with a capacity of transferring various biological materials such as microRNAs, proteins, and lipids among cells without direct cell-to-cell contact. Many cells in the nervous system have been shown to release EVs. These vesicles are involved in intercellular communication and a variety of biological processes such as modulation of immune response, signal transduction, and transport of genetic materials with low immun...
Source: Journal of Molecular Neuroscience - August 23, 2018 Category: Neuroscience Source Type: research

Caffeine Prevents Memory Impairment Induced by Hyperhomocysteinemia
Abstractl-Methionine chronic administration leads to impairment of memory. This impairment is due to the increase in the body oxidative stress, which damages neurons and prevents their firing. On the other hand, caffeine has antioxidant and neuroprotective effects that could prevent impairment of memory induced byl-methionine chronic administration. In the current study, this hypothesis was evaluated.l-methionine (1.7  g/kg/day) was orally administered to animals for 4 weeks and caffeine (0.3 g/L) treatment was added to the drinking water. The radial arm water maze (RAWM) was used to test spatial learning an...
Source: Journal of Molecular Neuroscience - August 23, 2018 Category: Neuroscience Source Type: research

Bioinformatics Analysis of Microarray Profiling Identifies That the miR-203-3p Target Ppp2ca Aggravates Seizure Activity in Mice
This study aimed to identify key genes (microRNA and messenger RNA (mRNA)) and associated signaling-regulated pathways in a drug-induced epilepsy model in mice by microarray profiling. The related microarray dataset of seizures was obtained from the NCBI Gene Expression Omnibus database (GEO), and differentially expressed genes (DEGs) between two control samples or multi-treated samples and samples were analyzed using the statistical software R. To identify the expected function of DEGs, Gene Set Enrichment Analysis (GSEA) was utilized to conduct Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG...
Source: Journal of Molecular Neuroscience - August 18, 2018 Category: Neuroscience Source Type: research

Genetic Risk Factors for Intracranial Aneurysm in the Kazakh Population
AbstractAn intracranial aneurysm (IA) is a weak or thin area on a blood vessel in the brain that balloons as it fills with blood. Genetic factors can influence the risk of developing an aneurism. The purpose of this study was to explore the relationship between single nucleotide polymorphisms (SNPs) and IA in Kazakh population. The patients were genotyped for 60 single nucleotide polymorphisms. Genotyping was performed on the QuantStudio 12K Flex (Life Technologies). A linear regression analysis found 13 SNPs ’ significant association with development and rupture of IA: the rs1800956 polymorphism of theENG gene, rs17...
Source: Journal of Molecular Neuroscience - August 18, 2018 Category: Neuroscience Source Type: research

The Heptahelical Domain of the Sweet Taste Receptor T1R2 Is a New Allosteric Binding Site for the Sweet Taste Modulator Amiloride That Modulates Sweet Taste in a Species-Dependent Manner
This study describes the species-dependent regulation of the response of sweet taste receptors by this sweet inhibitor. Amiloride inhibited the sweet taste response of humans and mice but not that of squirrel monkeys. Using human/squirrel monkey/mouse chimeric T1R2 and T1R3 receptors as well as the agonist perillartine (which can activate the single heptahelical domain of T1R2), we found that the heptahelical domain of T1R2 is the molecular determinant that mediates the species-dependent sensitivity to this sweet regulator. Compared to the sweet inhibitor lactisole (which acts on T1R3), amiloride has a different allosteric...
Source: Journal of Molecular Neuroscience - August 17, 2018 Category: Neuroscience Source Type: research

The Use of Multi-parametric Biomarker Profiles May Increase the Accuracy of ASD Prediction
In this study, we evaluate the usefulness of nine biomarkers and their association (combination) in predicting ASD onset and development. Data were analyzed using multiple independent mathematical and statistical approaches to verify the suitability of obtained results as predictive parameters. All biomarkers tested appeared useful in predicting ASD, particularly vitamin E, glutathione-S-transferase, and dopamine. Combining biomarkers into profiles improved the accuracy of ASD prediction but still failed to distinguish between participants with severe versus mild or moderate ASD. Library-based identification was effective ...
Source: Journal of Molecular Neuroscience - August 15, 2018 Category: Neuroscience Source Type: research

Pharmacological Comparisons Between Cannabidiol and KLS-13019
AbstractCannabidiol (CBD) exhibits neuroprotective properties in many experimental systems. However, development of CBD as a drug has been confounded by the following: (1) low potency; (2) a large number of molecular targets; (3) marginal pharmacokinetic properties; and (4) designation as a schedule 1 controlled substance. The present work compared the properties of CBD with a novel molecule (KLS-13019) that has structural similarities to CBD. The design strategy for KLS-13019 was to increase hydrophilicity while optimizing neuroprotective potency against oxidative stress toxicity relevant to hepatic encephalopathy. The pr...
Source: Journal of Molecular Neuroscience - August 14, 2018 Category: Neuroscience Source Type: research

Immunomodulatory Roles of PACAP and VIP: Lessons from Knockout Mice
AbstractA bidirectional cross-talk is established between the nervous and immune systems through common mediators including neuropeptides, neurotransmitters, and cytokines. Among these, PACAP and VIP are two highly related neuropeptides widely distributed in the organism with purported immunomodulatory actions. Due to their well-known anti-inflammatory properties, administration of these peptides has proven to be beneficial in models of acute and chronic inflammatory diseases. Nevertheless, the relevance of the endogenous source of these peptides in the modulation of immune responses remains to be elucidated. The developme...
Source: Journal of Molecular Neuroscience - August 13, 2018 Category: Neuroscience Source Type: research

Neuromuscular Junction Morphology and Gene Dysregulation in the Wobbler Model of Spinal Neurodegeneration
We examined biceps and end plate morphologies and monitored selected factors involved in end plate function. Structural volumes were determined from 3D reconstructions that were generated for the end plates. Wobbler mice exhibited size reductions of both the muscle fibers and the end plates within the biceps, and we found that the end plate volumes were the most sensitive indicator of the degeneration. Concurrently, we found increases in calcitonin gene-related peptide (CGRP) and its receptor in wobbler biceps and spinal cord. We also found increases in gene expression of two acetylcholine receptors within the wobbler bice...
Source: Journal of Molecular Neuroscience - August 13, 2018 Category: Neuroscience Source Type: research

Altered Notch Signaling in Developing Molar Teeth of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)-Deficient Mice
In this study, our main goal was to evaluate the possible effects of PACAP on Notch signaling pathway. Immunohistochemical staining was performed of Notch receptors (Notch1, 2, 3, 4), their ligands [delta-like protein (DLL)1, 3, 4, Jagged1, 2], and intracellular target molecules [CSL (CBF1 humans/Su (H)Drosophila/LAG1Caenorhabditis elegans transcription factor); TACE (TNF- α converting enzyme), NUMB] in molar teeth of 5-day-old WT, and homozygous and heterozygous PACAP-deficient mice. We measured immunopositivity in the enamel-producing ameloblasts and dentin-producing odontoblasts. Notch2 receptor and DLL1 expressio...
Source: Journal of Molecular Neuroscience - August 10, 2018 Category: Neuroscience Source Type: research

Long-Term Effects of Iloperidone on Cerebral Serotonin and Adrenoceptor Subtypes
We examined the long-term effects of multiple doses of iloperidone (0.5, 1.5, or 5  mg/kg) on serotonin (5-HT) 5-HT1A, 5-HT2A receptor subtypes, and adrenoceptors α1 and α2 subtypes. Rats received daily intraperitoneal injections of different doses of iloperiodone or vehicle for 4  weeks. Receptor autoradiography quantified the levels of 5-HT and adrenoceptors in medial prefrontal cortex (MPC), dorsolateral frontal cortex (DFC), caudate putamen (CPu), nucleus accumbens (NAc), and hippocampal CA1 (HIP-CA1) and CA3 (HIP-CA3) regions. Four weeks of iloperidone treatment signifi cantly and dose-dependentl...
Source: Journal of Molecular Neuroscience - August 9, 2018 Category: Neuroscience Source Type: research

Serum Coenzyme Q10 Is Associated with Clinical Neurological Outcomes in Acute Stroke Patients
This study aims at measuring serum concentration of CoQ10 along with major indicators of antioxidant and oxidant among patients within 24  h after onset of the stroke symptoms, and investigating their relation with the clinical status of patients. Serum levels of CoQ10, superoxide dismutase (SOD), and malondialdehyde (MDA) were measured in 76 patients and 34 healthy individuals. Severity of the neurological deficit, functional disabi lity, and cognitive status in ischemic subjects were respectively studied with the National Institutes of Health stroke scale (NIHSS), modified Rankin Scale (MRS), and Mini-Mental State E...
Source: Journal of Molecular Neuroscience - August 9, 2018 Category: Neuroscience Source Type: research

Correction to: Population-Based Analysis of Cluster Headache-Associated Genetic Polymorphisms
The original version of this article unfortunately contained mistakes in author group section. (Source: Journal of Molecular Neuroscience)
Source: Journal of Molecular Neuroscience - August 9, 2018 Category: Neuroscience Source Type: research

CYP27A1, CYP24A1, and RXR- α Polymorphisms, Vitamin D, and Multiple Sclerosis: a Pilot Study
AbstractMultiple sclerosis (MS) is a neurodegenerative autoimmune disease resulting from a complex interaction of genetic and environmental factors. Hypovitaminosis D seems to contribute to MS susceptibility as both an environmental and a genetic risk factor. The aim of our study was to investigate the association of SNPs in CYP27A1, CYP24A1, and RXR- α genes, vitamin D status, and MS risk. We performed a nested case-control study on patients with multiple sclerosis and healthy controls. Serum 25(OH)D3 levels and genotyping of CYP27A1, CYP24A1, and RXR- α -SNPs were investigated both in MS patients and in healt...
Source: Journal of Molecular Neuroscience - August 7, 2018 Category: Neuroscience Source Type: research

Alzheimer ’s Disease Risk Variant rs2373115 Regulates GAB2 and NARS2 Expression in Human Brain Tissues
AbstractGenetic association studies have identified significant association between theGAB2 rs2373115 variant and Alzheimer ’s disease (AD). However, it is unknown whether rs2373115 affects the regulation of nearby genes. Here, we evaluate the potential effect of rs2373115 on gene expression using multiple eQTL (expression quantitative trait loci) datasets from human brain tissues from the Mayo Clinic brain expression genome-wide association study (eGWAS), the UK Brain Expression Consortium (UKBEC), the Genotype-Tissue Expression (GTEx) project, and the Brain xQTL Serve. Our findings indicate that the rs2373115 C all...
Source: Journal of Molecular Neuroscience - August 7, 2018 Category: Neuroscience Source Type: research

Biglycan, a Nitric Oxide-Downregulated Proteoglycan, Prevents Nitric Oxide-Induced Neuronal Cell Apoptosis via Targeting Erk1/2 and p38 Signaling Pathways
AbstractNitric oxide (NO), a gaseous signaling molecule, induces apoptosis and mediates neurodegenerative diseases and brain injury. Biglycan (BGN), a member of the small leucine-rich proteoglycan family, was demonstrated to exert anti-apoptosis function in various disease models. However, little is known about the effect of BGN on NO-induced neurotoxicity. Here, for the first time, we reported that BGN protects against NO-induced apoptosis in human neuroblastoma SH-EP1 cells. This is supported by the finding that sodium nitroprusside (SNP), a NO donor, triggered downregulation of BGN in SH-EP1 cells, and over-expression o...
Source: Journal of Molecular Neuroscience - August 7, 2018 Category: Neuroscience Source Type: research

The Flavone Luteolin Improves Central Nervous System Disorders by Different Mechanisms: A Review
AbstractDevelopment and design of agents derived from natural sources with neuroprotective properties have received considerable attention. In the literature, it has been stated that these polyphenolic molecules have low adverse impacts and high efficacy when used in pathological conditions. Dietary flavonoids as a subgroup of polyphenols are bioactive products, extracted from several types of vegetables and fruits. Luteolin (3 ′,4′,5,7-tetrahydroxyflavone, LUT) is a widespread flavone known to have antioxidant and cytoprotective properties related to nuclear factor erythroid 2-related factor 2-(Nrf2) pathway. ...
Source: Journal of Molecular Neuroscience - August 6, 2018 Category: Neuroscience Source Type: research

Clinical, Molecular, and Computational Analysis Showed a Novel Homozygous Mutation Among the Substrate-Binding Site of ARSA Protein in Consanguineous Family with Late-Infantile MLD
AbstractMetachromatic leukodystrophy (MLD) is a neurodegenerative disorder characterized by progressive demyelination resulting from impaired degradation and thus the accumulation of cerebroside-3-sulfate (sulfatide). It is caused by the deficiency of arylsulfatase A (ARSA) enzyme which is encoded by theARSA gene. The present study reports the clinical, molecular, and bioinformatic investigation of three patients belonging to a consanguineous family with late-infantile MLD disorder. The results revealed a novel homozygous missense mutation c.699C>A (p.His231Gln) in exon 4 ofARSA gene in the three patients inherited from...
Source: Journal of Molecular Neuroscience - August 6, 2018 Category: Neuroscience Source Type: research

Identification of Critical Genes and miRNAs Associated with the Development of Parkinson ’s Disease
AbstractThe purpose of this study was to explore the key mechanism involved in the pathogenesis of Parkinson ’s disease (PD) based on microarray analysis. The expression profile data of GSE7621, which contained 9 substantia nigra tissues isolated from normals and 16 substantia nigra tissues isolated from PD patients, was obtained from Gene Expression Omnibus. The differentially expressed genes (DEGs) wer e screened, followed by functional enrichment analysis and protein-protein interaction (PPI) network construction. After the miRNAs regulating the DEGs were predicted, the miRNA-DEG regulatory network was then constr...
Source: Journal of Molecular Neuroscience - August 6, 2018 Category: Neuroscience Source Type: research

ORL 1 Activation Mediates a Novel ORL 1 Receptor Agonist SCH221510 Analgesia in Neuropathic Pain in Rats
AbstractOpioid receptor like 1 (ORL1) receptor activation displayed an anti-nociceptive effect at spinal level for acute and neuropathic pain. SCH221510, an orally active non-peptide ORL1 agonist, was reported to be effective in treating neuropathic pain. The present study used ORL1 antagonist and siRNA to investigate that ORL1 activation mediates intrathecal SCH221510 analgesia in neuropathic pain induced by chronic constrictive injury (CCI) to rat sciatic nerve. Paw withdrawal latency and 50% mechanical threshold were measured for thermal and mechanical hypersensitivity in rats. CCI significantly decreased paw withdrawal...
Source: Journal of Molecular Neuroscience - August 3, 2018 Category: Neuroscience Source Type: research

PAC1 Receptors: Shapeshifters in Motion
AbstractShapeshifters, in common mythology, are entities that can undergo multiple physical transformations. As our understanding of G protein-coupled receptors (GPCRs) has accelerated and been refined over the last two decades, we now understand that GPCRs are not static proteins, but rather dynamic structures capable of moving from one posture to the next, and adopting unique functional characteristics at each transition. This model of GPCR dynamics underlies our current understanding of biased agonism —how different ligands to the same receptor can generate different intracellular signals—and constitutive re...
Source: Journal of Molecular Neuroscience - August 3, 2018 Category: Neuroscience Source Type: research

Pituitary Adenylate Cyclase-Activating Peptide (PACAP) Signaling and the Dark Side of Addiction
AbstractWhile addiction to drugs of abuse represents a significant health problem worldwide, the behavioral and neural mechanisms that underlie addiction and relapse are largely unclear. The concept of thedark side of addiction, developed and explored by George Koob and colleagues, describes a systematic decrease in reward-related processing following drug self-administration and subsequent recruitment of anti-reward (i.e., stress) systems. Indeed, the activation of central nervous system (CNS) stress-response systems by drugs of abuse is contributory not only to mood and anxiety-related disorders but critical to both the ...
Source: Journal of Molecular Neuroscience - August 3, 2018 Category: Neuroscience Source Type: research

A Glutamate Transporter EAAT1 Gene Variant Influences Amygdala Functional Connectivity in Bipolar Disorder
AbstractBipolar disorder (BD) is a severe illness characterized by recurrent depressive and manic episodes and by emotional dysregulation. Altered cortico-limbic connectivity could account for typical symptoms of the disorder such as mood instability, emotional dysregulation, and cognitive deficits. Functional connectivity positively associated with glutamatergic neurotransmission. The inactivation of glutamate is handled by a series of glutamate transporters, among them, the excitatory amino acid transporter 1 (EAAT1) which is modulated by a SNP rs2731880 (C/T) where the C allele leads to increased EAAT1 expression and gl...
Source: Journal of Molecular Neuroscience - August 2, 2018 Category: Neuroscience Source Type: research

Clonidine Protects Against Neurotoxicity Induced by Sevoflurane Through NF- κB Signaling Inhibition and Proinflammatory Cytokine Release in Rats
AbstractExposure of neonatal animals to anesthetics may cause developmental functional changes and acute structural anomalies in the brain. Clonidine, an α2-adrenoceptor agonist, functions as an analgesic and sedative and protects against brain injury. Nevertheless, whether clonidine protects the developing brain from damage caused by sevoflurane (SEVO) anesthesia remains unclear. Seven-day-old rats were exposed to 3% SEVO for 6 h, during which tim e either clonidine or saline was injected three times. The arterial blood gases, respiratory rate, and anesthesia level of each rat were evaluated. Western blot analy...
Source: Journal of Molecular Neuroscience - August 2, 2018 Category: Neuroscience Source Type: research

Progress in Understanding the Relationship Between Circular RNAs and Neurological Disorders
AbstractCircular RNAs (circRNAs), a type of endogenous noncoding RNAs distinct from linear forms, are produced by backsplicing events within genes. circRNAs are structurally stable, highly conserved molecules found widely in organisms, and display tissue-type and developmental-stage specific expression patterns, which reveal their significant regulatory functions in gene expression. Based on accumulating evidence, some circRNAs are now believed to be a class of competitive endogenous RNAs that regulate gene expression. For example, circRNAs may prevent microRNAs from inhibiting target RNAs acting as microRNA sponges, or in...
Source: Journal of Molecular Neuroscience - August 1, 2018 Category: Neuroscience Source Type: research

A Novel scFv Anti-A β Antibody Reduces Pathological Impairments in APP/PS1 Transgenic Mice via Modulation of Inflammatory Cytokines and Aβ-related Enzymes
AbstractImmunotherapy for Alzheimer ’s disease (AD) remains promising in the improvement of cognition and memory via the clearing of amyloid-β protein (Aβ) in the AD brain, despite some side effects. Our previous studies demonstrated that the 31-35 sequence of the Aβ molecule was the shortest active center and that polyclonal ant i-Aβ31-35 antibody reduced neuronal apoptosis and cognitive impairments induced with acute Aβ application. The present study designed a novel single-chain variable fragment (scFv) monoclonal anti-Aβ31-35 antibody (scFv17) that specifically recognized extracellul...
Source: Journal of Molecular Neuroscience - July 31, 2018 Category: Neuroscience Source Type: research

Electroacupuncture Alleviated Neuronal Apoptosis Following Ischemic Stroke in Rats via Midkine and ERK/JNK/p38 Signaling Pathway
This study aimed to evaluate the effects of electroacupuncture (EA) intervention administered at rats of middle cerebral artery occlusion (MCAO)/reperfusion. Fifty-four male Sprague-Dawley rats were divided into three groups, consisting of sham group, MCAO/R group, and EA group. EA treatment at Quchi and Zusanli acupoints was applied in rats of EA group at 24  h after MCAO once per day for 3 days. Our results indicated that EA treatment reduced infarct volumes and neurological deficits, as well alleviated the apoptotic cells in peri-infarct cortex, indicating that EA exerted neuroprotective effect in cerebral isc...
Source: Journal of Molecular Neuroscience - July 31, 2018 Category: Neuroscience Source Type: research

PACAP/PAC1 Regulation of Inflammation via the Sympathetic Nervous System in a Model of Multiple Sclerosis
AbstractThe sympathetic nervous system (SNS) serves to maintain homeostasis of vital organ systems throughout the body, and its dysfunction plays a major role in human disease. The SNS also links the central nervous system to the immune system during different types of stress via innervation of the lymph nodes, spleen, thymus, and bone marrow. Previous studies have shown that pituitary adenylate cyclase-activating polypeptide (PACAP, gene name adcyap1) exhibits anti-inflammatory properties in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Because PACAP is known to regulate SNS function, we...
Source: Journal of Molecular Neuroscience - July 30, 2018 Category: Neuroscience Source Type: research

PACAP-Induced PAC1 Receptor Internalization and Recruitment of Endosomal Signaling Regulate Cardiac Neuron Excitability
AbstractPituitary adenylate cyclase-activating polypeptide (PACAP,Adcyap1) activation of PAC1 receptors (Adcyap1r1) significantly increases excitability of guinea pig cardiac neurons. This modulation of excitability is mediated in part by plasma membrane G protein-dependent activation of adenylyl cyclase and downstream signaling cascades, as well as by endosomal signaling mechanisms. PACAP/PAC1 receptor-mediated activation of plasma membrane adenylyl cyclase (AC) and the resulting increase in cellular cAMP enhances a hyperpolarization-induced nonselective cationic currentIh, which contributes to the PACAP-induced increase ...
Source: Journal of Molecular Neuroscience - July 27, 2018 Category: Neuroscience Source Type: research

The Potential Contribution of microRNAs in Anti-cancer Effects of Aurora Kinase Inhibitor (AZD1152-HQPA)
AbstractNeuroblastoma (NB) remains the critical challenge in pediatric oncology. It has the highest rate of spontaneous regression among all human cancers. Aurora kinase B (AURKB), a crucial regulator of malignant mitosis, is involved in chromosome segregation and cytokinesis. AZD1152-HQPA (Barasertib) is a small selective inhibitor of AURKB activity and currently bears clinical assessment for several malignancies. Studies suggested that microRNAs are involved in the pathobiology and chemoresistance of neuroblastoma. In the present study, we first investigated the restrictive potentials of AZD1152-HQPA on cell viability, c...
Source: Journal of Molecular Neuroscience - July 26, 2018 Category: Neuroscience Source Type: research

Novel and Recurring Disease-Causing NF1 Variants in Two Chinese Families with Neurofibromatosis Type 1
This study aims to discover the disease-causing variants responsible for NF1 in two Han Chinese families by using exome sequencing combined with Sanger sequencing. A recurrent missense variant c.269T>C (p.Leu90Pro) and a novel nonsense variant c.2993dupA (p.Tyr998*) in theNF1 gene were identified. These variants co-segregated with the disorder in the pedigrees and were absent in the normal controls. The results broaden theNF1 mutation spectrum responsible for NF1. This may be helpful in genetic counseling, clinical management, and gene-targeted therapies for NF1. (Source: Journal of Molecular Neuroscience)
Source: Journal of Molecular Neuroscience - July 25, 2018 Category: Neuroscience Source Type: research

Association Between Objectively Measured Physical Activity and Plasma BDNF in Adolescents: DADOS Study
AbstractBrain-derived neurotrophic factor (BDNF) is suggested to play a key role in moderating the benefits of physical activity (PA) on cognition. Previous research found that PA may have an impact on peripheral BDNF expression. The aim of our study was to analyze the association between objectively measured PA with circulating BDNF in a group of active adolescents. Two hundred thirty-four adolescents (132 boys) aged 13.9  ± 0.3 years old from the DADOS study were included in this cross-sectional analysis. PA was assessed by GENEActiv triaxial accelerometer. Participants wore the accelerometer on...
Source: Journal of Molecular Neuroscience - July 23, 2018 Category: Neuroscience Source Type: research

Photobiomodulation Therapy Attenuates Hypoxic-Ischemic Injury in a Neonatal Rat Model
AbstractPhotobiomodulation (PBM) has been demonstrated as a neuroprotective strategy, but its effect on perinatal hypoxic-ischemic encephalopathy is still unknown. The current study was designed to shed light on the potential beneficial effect of PBM on neonatal brain injury induced by hypoxia ischemia (HI) in a rat model. Postnatal rats were subjected to hypoxic-ischemic insult, followed by a 7-day PBM treatment via a continuous wave diode laser with a wavelength of 808  nm. We demonstrated that PBM treatment significantly reduced HI-induced brain lesion in both the cortex and hippocampal CA1 subregions. Molecular st...
Source: Journal of Molecular Neuroscience - July 22, 2018 Category: Neuroscience Source Type: research

Implication of OPRM1 A118G Polymorphism in Opioids Addicts in Pakistan: In vitro and In silico Analysis
AbstractSingle nucleotide polymorphism inOPRM1 gene is associated with hedonic and reinforcing consequences of opioids. Risk and protective alleles may vary in different populations. One hundred healthy controls and 100 opioids (predominantly heroin) addicts from Pakistani origin were genotyped for A118G (N40D) polymorphism inOPRM1. Structural and functional impact of the polymorphism on encoded protein was predicted by in silico analysis. Results show significant association between homozygous GG genotype and opioid addiction in Pakistani population (p value  = 0.016). In silico analysis by SIFT (TI =...
Source: Journal of Molecular Neuroscience - July 22, 2018 Category: Neuroscience Source Type: research

Homocysteine and A2A-D2 Receptor-Receptor Interaction at Striatal Astrocyte Processes
AbstractThe interaction between adenosine A2A and dopamine D2 receptors in striatal neurons is a well-established phenomenon and has opened up new perspectives on the molecular mechanisms involved in Parkinson ’s disease. However, it has barely been investigated in astrocytes. Here, we show by immunofluorescence that both A2A and D2 receptors are expressed in adult rat striatal astrocytes in situ, and investigate on presence, function, and interactions of the receptors in the astrocyte processes—acute ly prepared from the adult rat striatum—and on the effects of homocysteine on the A2A-D2 receptor-recepto...
Source: Journal of Molecular Neuroscience - July 20, 2018 Category: Neuroscience Source Type: research

Over-Expressed FEZF1 Predicts a Poor Prognosis in Glioma and Promotes Glioma Cell Malignant Biological Properties by Regulating Akt-ERK Pathway
AbstractFEZ family zinc finger 1 (FEZF1) is an essential transcription factor during olfactory development. In gastrointestinal tumors, FEZF1 plays an oncogenic role through DNA demethylation. However, the role of FEZF1 in the prognosis of human glioma prognosis remains unclear. In this research, we discovered that FEZF1 was significantly increased in glioma tissues in contrast to normal brain tissues (NBTs;P 
Source: Journal of Molecular Neuroscience - July 20, 2018 Category: Neuroscience Source Type: research