Correction to: The Medial Septum Is Insulin Resistant in the AD Presymptomatic Phase: Rescue by Nerve Growth Factor-Driven IRS 1 Activation
The authors, due to the change in one of the University name at the affiliation, hereby correct the proof. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 21, 2019 Category: Neurology Source Type: research

Effect of the HDAC Inhibitor, Sodium Butyrate, on Neurogenesis in a Rat Model of Neonatal Hypoxia –Ischemia: Potential Mechanism of Action
AbstractNeonatal hypoxic –ischemic (HI) brain injury likely represents the major cause of long-term neurodevelopmental disabilities in surviving babies. Despite significant investigations, there is not yet any known reliable treatment to reduce brain damage in suffering infants. Our recent studies in an animal model of HI revealed the therapeutic potential of a histone deacetylase inhibitor (HDACi). The neuroprotective action was connected with the stimulation of neurogenesis in the dentate gyrus subgranular zone. In the current study, we investigated whether HDACi—sodium butyrate (SB)—would also lead to ...
Source: Molecular Neurobiology - February 14, 2019 Category: Neurology Source Type: research

Transferrin Enhances Microglial Phagocytic Capacity
AbstractTransferrin (Tf) is a glycoprotein playing a critical role in iron homeostasis and transport and distribution throughout the body and within tissues and cells. This molecule has been shown to accelerate the process of myelination and remyelination in the central nervous system (CNS) in vivo and induce oligodendroglial cell maturation in vitro. While the mechanisms involved in oligodendroglial precursor cell (OPC) differentiation have not been fully elucidated yet, our group has previously described the first molecular events taking place in OPC in response to extracellular Tf. Here, we show the effect of Tf on the ...
Source: Molecular Neurobiology - February 13, 2019 Category: Neurology Source Type: research

Oxytocin Neurons Enable Melanocortin Regulation of Male Sexual Function in Mice
AbstractThe melanocortin pathway has been implicated in both metabolism and sexual function. When the melanocortin 4 receptor (MC4R) is knocked out globally, male mice display obesity, low sexual desire, and copulatory difficulties; however, it is unclear whether these phenotypes are interdependent. To elucidate the neuronal circuitry involved in sexual dysfunction in MC4R knockouts, we re-expressed the MC4R in these mice exclusively on Sim1 neurons (tbMC4RSim1 mice) or on a subset of Sim1 neurons, namely oxytocin neurons (tbMC4Roxt mice). The groups were matched at young ages to control for the effects of obesity. Interes...
Source: Molecular Neurobiology - February 12, 2019 Category: Neurology Source Type: research

Hesperetin Confers Neuroprotection by Regulating Nrf2/TLR4/NF- κB Signaling in an Aβ Mouse Model
AbstractHesperetin is a bioactive flavonoid in the body, produced from hesperidin. No comprehensive studies have shown its protective effects in neurodegenerative disorders. Here, we hypothesized that hesperetin may protect the mice brain against A β-induced neurodegeneration. Twenty-four hours after intracerebroventricular injection of Aβ1-42, the treated group was injected hesperetin. For in vitro experiments, HT22 and BV-2 cells were used. Immunoblot, immunofluorescence, and behavioral analyses were used to evaluate the different paramete rs. Our results indicated that hesperetin significantly attenuated oxida...
Source: Molecular Neurobiology - February 12, 2019 Category: Neurology Source Type: research

Spike-Related Electrophysiological Identification of Cultured Hippocampal Excitatory and Inhibitory Neurons
AbstractCultured hippocampal neurons represent the most widely used experimental substrate for in vitro electrophysiological studies. Nevertheless, in most cases, the nature of neuron under study is not identified as excitatory or inhibitory, or even worse, recorded neurons are considered as excitatory because of the paucity of GABAergic interneurons. Thus, the definition of reliable criteria able to guarantee an unequivocal identification of excitatory and inhibitory cultured hippocampal neurons is an unmet need. To reach this goal, we compared the electrophysiological properties and the localization and size of the axon ...
Source: Molecular Neurobiology - February 12, 2019 Category: Neurology Source Type: research

Transcriptional Signatures of Cognitive Impairment in Rat Exposed to Prenatal Stress
AbstractExposure to adverse events during gestation has detrimental effects on the maturation of specific brain networks, triggering changes in the expression of several stress-related mechanisms that may lead to long-lasting functional consequences, including cognitive deterioration. On these bases, the aim of the present study was to investigate the effects of early-life stress exposure on cognition and to explore potential molecular mechanisms contributing to the long-term functional impairment. We found that exposure to prenatal stress, a well-established animal model of early-life adversity, produces a significant dis...
Source: Molecular Neurobiology - February 11, 2019 Category: Neurology Source Type: research

Changes in Dendritic Spine Density and Inhibitory Perisomatic Connectivity onto Medium Spiny Neurons in l -Dopa-Induced Dyskinesia
AbstractUsing bacterial artificial chromosome –double transgenic mice expressing tdTomato in D1 receptor-medium spiny neurons (MSNs) and enhanced green fluorescent protein in D2 receptor-MSNs, we have studied changes in spine density and perisomatic GABAergic boutons density in MSNs of both the D1R and D2R pathways, in an experimental model o f parkinsonism (mouse injected with 6-hydroxydopamine in the medial forebrain bundle), both in the parkinsonian and dyskinetic condition induced byl-DOPA treatment. To assess changes in perisomatic GABAergic connectivity onto MSNs, we measured the number of contacts originated f...
Source: Molecular Neurobiology - February 11, 2019 Category: Neurology Source Type: research

Tactile Stimulation on Adulthood Modifies the HPA Axis, Neurotrophic Factors, and GFAP Signaling Reverting Depression-Like Behavior in Female Rats
AbstractDepression is a common psychiatric disease which pharmacological treatment relieves symptoms, but still far from ideal. Tactile stimulation (TS) has shown beneficial influences in neuropsychiatric disorders, but the mechanism of action is not clear. Here, we evaluated the TS influence when applied on adult female rats previously exposed to a reserpine-induced depression-like animal model. Immediately after reserpine model (1  mg/kg/mL, 1×/day, for 3 days), femaleWistar rats were submitted to TS (15  min, 3×/day, for 8 days) or not (unhandled). Imipramine (10 mg/kg/mL) was used a...
Source: Molecular Neurobiology - February 11, 2019 Category: Neurology Source Type: research

Water-Soluble Arginyl –Diosgenin Analog Attenuates Hippocampal Neurogenesis Impairment Through Blocking Microglial Activation Underlying NF-κB and JNK MAPK Signaling in Adult Mice Challenged by LPS
AbstractMicroglia-mediated neuroinflammatory responses are well known to inhibit neurogenesis in the dentate gyrus (DG) of the adult hippocampus, and growing evidence indicates that therapeutic intervention to suppress microglial activation could be an effective strategy for restoring the impaired neurogenesis and memory performance. In the present study, we investigated the effects of water-soluble arginyl –diosgenin analog (Arg-DG) on the adult hippocampal neurogenesis using a central LPS-induced inflammatory mice model, along with the fundamental mechanisms in vivo and in vitro using LPS-stimulated microglial BV2 ...
Source: Molecular Neurobiology - February 11, 2019 Category: Neurology Source Type: research

Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated Memory
AbstractDopamine (DA) neurons in the ventral tegmental area (VTA) are well-known components of the brain involved in reward-related behaviors and participate in the generation of new memories. Much attention has been focused to understand how DA neurons integrate a diversity of afferent signals with local excitatory and inhibitory influences regulated by somatodendritic release of dopamine. However, the mechanisms that actively forget rewarding information are still terra incognita. Using rodents in the conditioned place preference (CPP) behavioral task, we show that during acquisition D1-type DA receptors (D1R) in the VTA...
Source: Molecular Neurobiology - February 9, 2019 Category: Neurology Source Type: research

The ERK Pathway: Molecular Mechanisms and Treatment of Depression
AbstractMajor depressive disorder is a chronic debilitating mental illness. Its pathophysiology at cellular and molecular levels is incompletely understood. Increasing evidence supports a pivotal role of the mitogen-activated protein kinase (MAPK), in particular the extracellular signal-regulated kinase (ERK) subclass of MAPKs, in the pathogenesis, symptomatology, and treatment of depression. In humans and various chronic animal models of depression, the ERK signaling was significantly downregulated in the prefrontal cortex and hippocampus, two core areas implicated in depression. Inhibiting the ERK pathway in these areas ...
Source: Molecular Neurobiology - February 9, 2019 Category: Neurology Source Type: research

Microglial Depletion with Clodronate Liposomes Increases Proinflammatory Cytokine Levels, Induces Astrocyte Activation, and Damages Blood Vessel Integrity
In this study, injecting 1  μL of clodronate liposomes (7 μg/μL) into the striatum of mice caused ablation of microglia at 1 day that persisted for 3 days. Microglia reappeared in the boundary regions of microglia elimination after 5 days. Importantly, we observed an increase in proinflammatory cytokine levels and an increase in neural/glial antigen 2 and glial fibrillary acidic protein expression in the perilesional region. In contrast, expression levels of myelin basic protein, microtubule-associated protein 2, and postsynaptic protein-95 decreased in the periphery of regions where micro...
Source: Molecular Neurobiology - February 8, 2019 Category: Neurology Source Type: research

Pathological Alterations of Tau in Alzheimer ’s Disease and 3xTg-AD Mouse Brains
AbstractMicrotubule-associated protein tau in Alzheimer ’s disease (AD) brain is hyperphosphorylated, truncated, and aggregated into neurofibrillary tangles. Oligomeric and hyperphosphorylated tau (Oligo-tau) isolated from AD brain captures and templates normal tau into filaments both in vitro and in vivo; this prion-like activity is believed to be res ponsible for the progression of neurofibrillary pathology in AD. The 3xTg-AD mouse model develops both Aβ and tau pathologies and thus gains popularity in preclinical studies of AD. Despite the histopathological similarity of the 3xTg-AD model to AD, biochemical a...
Source: Molecular Neurobiology - February 8, 2019 Category: Neurology Source Type: research

Systematic Review of miRNA as Biomarkers in Alzheimer ’s Disease
AbstractCurrently there are 850,000 people with Alzheimer ’s disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer’s disease is characterised by the accumulation of amyloid-beta plaques and hyperphosphorylated tau in the brain causing a progressive decline in cognitive impairment. Small non-coding microRNA (miRNA) sequences have b een found to be deregulated in the peripheral blood of Alzheimer patients. A systematic review was conducted to extract all miRNA found to be significantly deregulated in the peripheral blood. These deregulated miRNAs were cross-referenced against the miRNAs dere...
Source: Molecular Neurobiology - February 8, 2019 Category: Neurology Source Type: research

Immuno-Pharmacological Characterization of Presynaptic GluN3A-Containing NMDA Autoreceptors: Relevance to Anti-NMDA Receptor Autoimmune Diseases
AbstractMouse hippocampal glutamatergic nerve endings express presynaptic release-regulating NMDA autoreceptors (NMDARs). The presence of GluN1, GluN2A, GluN2B, and GluN3A subunits in hippocampal vesicular glutamate transporter type 1-positive synaptosomes was confirmed with confocal microscopy. GluN2C, GluN2D, and GluN3B immunopositivity was scarcely present. Incubation of synaptosomes with the anti-GluN1, the anti-GluN2A, the anti-GluN2B, or the anti-GluN3A antibody prevented the 30  μM NMDA/1 μM glycine-evoked [3H]d-aspartate ([3H]d-ASP) release. The NMDA/glycine-evoked [3H]d-ASP release was reduced by i...
Source: Molecular Neurobiology - February 7, 2019 Category: Neurology Source Type: research

Copper Binding Regulates Cellular Prion Protein Function
AbstractThe cellular prion protein (PrPC), mainly known for its role in neurodegenerative diseases, is involved in several physiological processes including neuritogenesis. In addition, its ability to bind copper or zinc has been suggested for its role in metal homeostasis. Although PrPC has been known as a copper-binding molecule, little is known about how copper can affect PrPC physiological functions. By combining genomic approaches, cellular assays, and focal stimulation technique, we found that PrPC neuritogenesis function is directly influenced by N-terminal copper-binding amino acids. Several recombinant mouse PrP (...
Source: Molecular Neurobiology - February 7, 2019 Category: Neurology Source Type: research

CHRM2 Genotype Affects Inhibitory Control Mechanisms During Cognitive Flexibility
AbstractThe cholinergic system is one of the most important neurotransmitter systems, but knowledge about the relevance of the cholinergic muscarinergic receptor system for cognitive functions is still scarce. Evidence suggests that the cholinergic muscarinic 2 receptor (CHRM2) plays an important role in the processing of cueing/prior information that help to increase the efficacy of lower-level attentional processes. In the current study, we investigated whether this is also the case for higher-level cognitive flexibility mechanisms. To this end, we testedN = 210 healthy adults with a backward inhibition tas...
Source: Molecular Neurobiology - February 7, 2019 Category: Neurology Source Type: research

Correction to: Nanocarrier-Mediated Delivery of CORM-2 Enhances Anti-Allodynic and Anti-Hyperalgesic Effects of CORM-2
The original version of this article, the name of author was incorrectely presented. That is Kyungjae Won (K. Won) should be presented asJae Won Kyung (J.W. Kyung). (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 7, 2019 Category: Neurology Source Type: research

Rab18 Collaborates with Rab7 to Modulate Lysosomal and Autophagy Activities in the Nervous System: an Overlapping Mechanism for Warburg Micro Syndrome and Charcot-Marie-Tooth Neuropathy Type 2B
AbstractMutations inRAB18, a member of small G protein, cause Warburg micro syndrome (WARBM), whose clinical features include vision impairment, postnatal microcephaly, and lower limb spasticity. Previously, ourRab18−/− mice exhibited hind limb weakness and spasticity as well as signs of axonal degeneration in the spinal cord and lumbar spinal nerves. However, the cellular and molecular function of RAB18 and its roles in the pathogenesis of WARBM are still not fully understood. Using immunofluorescence staining and expression of Rab18 and organelle markers, we find that Rab18 associates with lysosomes and activ...
Source: Molecular Neurobiology - February 5, 2019 Category: Neurology Source Type: research

Wide Profiling of Circulating MicroRNAs in Spinocerebellar Ataxia Type 7
In this study, we showed, to our knowledge for the first time, the expression profile of circulating miRNAs in SCA7. Using the TaqMan profiling low density array (TLDA), we found 71 differentially expressed miRNAs in the plasma of SCA7 patients, compared with healthy controls. The reliability of TLDA data was validated independently by quantitative real-time polymerase chain reaction in an independent cohort of patients and controls. We identified four validated miRNAs that possesses the diagnostic value to discriminate between healthy controls and patients (hsa-let-7a-5p, hsa-let7e-5p, hsa-miR-18a-5p, and hsa-miR-30b-5p)....
Source: Molecular Neurobiology - February 5, 2019 Category: Neurology Source Type: research

Current Understanding of the Role of Neuronal Calcium Sensor 1 in Neurological Disorders
AbstractNeuronal calcium sensor 1 (NCS-1) is a high-affinity calcium-binding protein and its ubiquitous expression in the nervous system implies a wide range of functions. To date, it has been implicated in regulation of calcium channels in both axonal growth cones and presynaptic terminals, pre- and postsynaptic plasticity mechanisms, learning and memory behaviors, dopaminergic signaling, and axonal regeneration. This review summarizes these functions and relates them to several diseases in which NCS-1 plays a role, such as schizophrenia and bipolar disorder, X-linked mental retardation and fragile X syndrome, and spinal ...
Source: Molecular Neurobiology - February 4, 2019 Category: Neurology Source Type: research

Blood-Based Biomarkers in High Grade Gliomas: a Systematic Review
AbstractHigh-grade gliomas (HGG) are the most common malignant primary brain tumor in adults. During the course of disease, several challenges occur, like measuring tumor burden, monitoring of treatment response, estimating the patient ’s prognosis, and distinguishing between true progression and pseudo-progression. So far, no blood-based biomarker has been established in the clinical routine to address these challenges. The aim of this systematic review was to analyze the present evidence on blood-based biomarkers for HGG. We s ystematically searched in PubMed, Web of Sciences, Scopus, and Cochrane Library databases...
Source: Molecular Neurobiology - February 4, 2019 Category: Neurology Source Type: research

Pluripotent Stem Cells as Models of Retina Development
AbstractThe ability of pluripotent stem cells (PSCs) to differentiate into retinal tissue has led to many attempts to direct this process to yield specific retinal cell types. The ability to do so would greatly impact both the study of normal retina development in model systems that can be precisely controlled and the generation of a homogeneous population of cells optimized for transplantation in cell replacement therapy. Thus far, many reviews have focused on the translational potential of PSC retinal studies. Here, we focus on the former by summarizing the advances and reflecting on the current limitations to using in v...
Source: Molecular Neurobiology - February 4, 2019 Category: Neurology Source Type: research

Cyclooxygenase (COX) Inhibition by Acetyl Salicylic Acid (ASA) Enhances Antitumor Effects of Nitric Oxide in Glioblastoma In Vitro
In this study, we show that pretreatment with acetyl salicylic acid (ASA) enhanced the c ytotoxic antitumor effect of NO in vitro. Combination of low doses of JS-K and ASA revealed a dose-dependent synergistic increase of necrotic cell death under circumvention of classical apoptosis and alteration of the metabolic calcium level. These findings provide an opportunity to improve currentl y used therapeutic strategies in the treatment of gliomas with a well-established remedy. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 4, 2019 Category: Neurology Source Type: research

Prions Strongly Reduce NMDA Receptor S-Nitrosylation Levels at Pre-symptomatic and Terminal Stages of Prion Diseases
We report that hippocampal NMDAR S-nitrosylation is greatly reduced in all three prion strain infections in both pre-symptomatic and terminal stages of mouse disease. Indeed, we show that NMDAR S-nitrosylation dysregulation affecting prion-inoculated animals precedes the appearance of clinical signs of disease and visible neuropathological changes, such as PrPSc accumulation and deposition. The pre-symptomatic reduction of NMDAR S-nitrosylation in prion-infected mice may be a possible cause of neuronal death in prion pathology, and it might contribute to the pathology progression opening new therapeutic strategies against ...
Source: Molecular Neurobiology - February 1, 2019 Category: Neurology Source Type: research

Upregulation of Proteolytic Pathways and Altered Protein Biosynthesis Underlie Retinal Pathology in a Mouse Model of Alzheimer ’s Disease
AbstractIncreased amyloid β (Aβ) aggregation is a hallmark feature of Alzheimer’s disease (AD) pathology. The APP/PS1 mouse model of AD exhibits accumulation of Aβ in the retina and demonstrates reduced retinal function and other degenerative changes. The overall molecular effects of AD pathology on the retina remain un determined. Using a proteomics approach, this study assessed the molecular effects of Aβ accumulation and progression of AD pathology on the retina. Retinal tissues from younger (2.5 months) and older 8-month APP/PS1 mice were analysed for protein expression changes. A multipl...
Source: Molecular Neurobiology - February 1, 2019 Category: Neurology Source Type: research

Correction to: In Vitro Seeding Activity of Glycoform-Deficient Prions from Variably Protease-Sensitive Prionopathy and Familial CJD Associated with PrP V180I Mutation
The original version of this article unfortunately contained a mistake. The email address Dr. Wen-Quan Zou, one of the corresponding authors should be written as “wxz6@case.edu” instead of “wxz@case.edu”. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 1, 2019 Category: Neurology Source Type: research

Sex-Dependent Sensory Phenotypes and Related Transcriptomic Expression Profiles Are Differentially Affected by Angelman Syndrome
AbstractAngelman syndrome (AS) is a genetic disorder which entails autism, intellectual disability, lack of speech, motor deficits, and seizure susceptibility. It is caused by the lack of UBE3A protein expression, which is an E3-ubiquitin ligase. Despite AS equal prevalence in males and females, not much data on how sex affects the syndrome was reported. In the herein study, we thoroughly characterized many behavioral phenotypes of AS mice. The behavioral data acquired was analyzed with respect to sex. In addition, we generated a new mRNA sequencing dataset. We analyzed the coding transcriptome expression profiles with res...
Source: Molecular Neurobiology - January 31, 2019 Category: Neurology Source Type: research

Inhibition of Semaphorin3A Promotes Ocular Dominance Plasticity in the Adult Rat Visual Cortex
AbstractPerineuronal nets (PNNs) are condensed structures in the extracellular matrix that mainly surround GABA-ergic parvalbumin-positive interneurons in the adult brain. Previous studies revealed a parallel between PNN formation and the closure of the critical period. Moreover, ocular dominance plasticity is enhanced in response to PNN manipulations in adult animals. However, the mechanisms through which perineuronal nets modulate plasticity are still poorly understood. Recent work indicated that perineuronal nets may convey molecular signals by binding and storing proteins with important roles in cellular communication....
Source: Molecular Neurobiology - January 31, 2019 Category: Neurology Source Type: research

Aluminum in Neurological and Neurodegenerative Disease
AbstractWith continuing cooperation from 18 domestic and international brain banks over the last 36  years, we have analyzed the aluminum content of the temporal lobe neocortex of 511 high-quality human female brain samples from 16 diverse neurological and neurodegenerative disorders, including 2 groups of age-matched controls. Temporal lobes (Brodmann areas A20–A22) were selected for analysis because of their availability and their central role in massive information-processing operations including efferent-signal integration, cognition, and memory formation. We used the analytical technique of (i) Zeeman-type ...
Source: Molecular Neurobiology - January 31, 2019 Category: Neurology Source Type: research

Fingolimod Suppresses the Proinflammatory Status of Interferon- γ-Activated Cultured Rat Astrocytes
AbstractAstroglia, the primary homeostatic cells of the central nervous system, play an important role in neuroinflammation. They act as facultative immunocompetent antigen-presenting cells (APCs), expressing major histocompatibility complex (MHC) class II antigens upon activation with interferon (IFN)- γ and possibly other proinflammatory cytokines that are upregulated in disease states, including multiple sclerosis (MS). We characterized the anti-inflammatory effects of fingolimod (FTY720), an established drug for MS, and its phosphorylated metabolite (FTY720-P) in IFN-γ-activated cultured rat astrocytes. The...
Source: Molecular Neurobiology - January 30, 2019 Category: Neurology Source Type: research

ROS-Induced Activation of DNA Damage Responses Drives Senescence-Like State in Postmitotic Cochlear Cells: Implication for Hearing Preservation
We examined whether ROS-induced DNA damage response drives cochlear cell senescence and contributes to ARHL from the cellular up to the system level. Our results revealed that sublethal concentrations of hydrogen peroxide (H2O2) exposure initiated a DNA damage response illustrated by increased γH2AX and 53BP1 expression and foci formation mainly in sensory hair cells, together with increased levels of p-Chk2 and p53. Interestingly, postmitotic cochlear cells exposed to H2O2 displayed key hallmarks of senescent cells, including dramatically increased levels of p21, p38, and p-p38 expression, concomitant with decreased...
Source: Molecular Neurobiology - January 28, 2019 Category: Neurology Source Type: research

Altered Nup153 Expression Impairs the Function of Cultured Hippocampal Neural Stem Cells Isolated from a Mouse Model of Alzheimer ’s Disease
AbstractImpairment of adult hippocampal neurogenesis is an early event in Alzheimer ’s disease (AD), playing a crucial role in cognitive dysfunction associated with this pathology. However, the mechanisms underlying defective neurogenesis in AD are still unclear. Recently, the nucleoporin Nup153 has been described as a new epigenetic determinant of adult neural stem cell (NSC) ma intenance and fate. Here we investigated whether Nup153 dysfunction could affect the plasticity of NSCs in AD. Nup153 expression was strongly reduced in AD-NSCs, as well as its interaction with the transcription factor Sox2, a master regulat...
Source: Molecular Neurobiology - January 28, 2019 Category: Neurology Source Type: research

A Targeted Mutation Disrupting Mitochondrial Complex IV Function in Primary Afferent Neurons Leads to Pain Hypersensitivity Through P2Y 1 Receptor Activation
AbstractAs mitochondrial dysfunction is evident in neurodegenerative disorders that are accompanied by pain, we generated inducible mutant mice with disruption of mitochondrial respiratory chain complex IV, by COX10 deletion limited to sensory afferent neurons through the use of anAdvillin Cre-reporter. COX10 deletion results in a selective energy-deficiency phenotype with minimal production of reactive oxygen species. Mutant mice showed reduced activity of mitochondrial respiratory chain complex IV in many sensory neurons, increased ADP/ATP ratios in dorsal root ganglia and dorsal spinal cord synaptoneurosomes, as well as...
Source: Molecular Neurobiology - January 28, 2019 Category: Neurology Source Type: research

CTGF/CCN2 from Skeletal Muscle to Nervous System: Impact on Neurodegenerative Diseases
AbstractConnective tissue growth factor (CTGF/CCN2) is a matricellular protein that belongs to the CCN family of proteins. Since its discovery, it has been linked to cellular processes such as cell proliferation, differentiation, adhesion, migration, and synthesis of extracellular matrix (ECM) components, among others. The pro-fibrotic role of CTGF/CCN2 has been well-studied in several pathologies characterized by the development of fibrosis. Reduction of CTGF/CCN2 levels inmdx mice, a murine model for Duchenne muscular dystrophy (DMD), decreases fibrosis and improves skeletal muscle phenotype and function. Recently, it ha...
Source: Molecular Neurobiology - January 28, 2019 Category: Neurology Source Type: research

Targeting CB 1 and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson ’s Disease
AbstractCannabinoid CB1 receptors (CB1R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson ’s disease (PD), one of the most prevalent neurodegenerative diseases in developed countries. The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, MPP+, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter. The SH-SY5Y cell line model was used as it expresses DAT and, therefore, is able to uptake MPP+ that inhibits complex I of the respiratory mi...
Source: Molecular Neurobiology - January 28, 2019 Category: Neurology Source Type: research

A Novel Divergent Gene Transcription Paradigm —the Decisive, Brain-Specific, Neural |-Srgap2–Fam72a-| Master Gene Paradigm
AbstractBrain development and repair largely depend on neural stem cells (NSCs). Here, we suggest that two genes, i.e., Srgap2 (SLIT-ROBO Rho GTPase –activating protein 2) and Fam72a (family with sequence similarity to 72, member A), constitute a single, NSC-specific, |-Srgap2–Fam72a-| master gene pair co-existing in reciprocal functional dependency. This gene pair has a dual, commonly used, intergenic region (IGR) promotor, which is a prere quisite in controlling human brain plasticity. We applied fluorescence cellular microscopy and fluorescence-activated cell sorting (FACS) to assess rat |-Srgap2–Fam72...
Source: Molecular Neurobiology - January 26, 2019 Category: Neurology Source Type: research

Socioeconomic Deprivation, Adverse Childhood Experiences and Medical Disorders in Adulthood: Mechanisms and Associations
AbstractSevere socioeconomic deprivation (SED) and adverse childhood experiences (ACE) are significantly associated with the development in adulthood of (i) enhanced inflammatory status and/or hypothalamic –pituitary–adrenal (HPA) axis dysfunction and (ii) neurological, neuroprogressive, inflammatory and autoimmune diseases. The mechanisms by which these associations take place are detailed. The two sets of consequences are themselves strongly associated, with the first set likely contributing to the second. Mechanisms enabling bidirectional communication between the immune system and the brain are described, i...
Source: Molecular Neurobiology - January 26, 2019 Category: Neurology Source Type: research

JNK Isoforms Are Involved in the Control of Adult Hippocampal Neurogenesis in Mice, Both in Physiological Conditions and in an Experimental Model of Temporal Lobe Epilepsy
AbstractNeurogenesis in the adult dentate gyrus (DG) of the hippocampus allows the continuous generation of new neurons. This cellular process can be disturbed under specific environmental conditions, such as epileptic seizures; however, the underlying mechanisms responsible for their control remain largely unknown. Although different studies have linked the JNK (c-Jun-N-terminal-kinase) activity with the regulation of cell proliferation and differentiation, the specific function of JNK in controlling adult hippocampal neurogenesis is not well known. The purpose of this study was to analyze the role of JNK isoforms (JNK1/J...
Source: Molecular Neurobiology - January 26, 2019 Category: Neurology Source Type: research

Impaired Pentose Phosphate Pathway in the Spinal Cord of the hSOD1 G93A Mouse Model of Amyotrophic Lateral Sclerosis
AbstractImpairments in energy metabolism in amyotrophic lateral sclerosis (ALS) have long been known. However, the changes in the energy-producing pathways in ALS are not comprehensively understood. To investigate specific alterations in glucose metabolism in glycolytic, pentose phosphate, and TCA cycle pathways, we injected uniformly labeled [U-13C]glucose to wild-type and hSOD1G93A mice at symptom onset (80  days). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), levels of metabolites were determined in extracts of the cortex and spinal cord. In addition, the activities of several enzymes involved in...
Source: Molecular Neurobiology - January 26, 2019 Category: Neurology Source Type: research

Mechanisms Associated with Type 2 Diabetes as a Risk Factor for Alzheimer-Related Pathology
AbstractCurrent evidence suggests dementia and pathology in Alzheimer ’s Disease (AD) are both dependent and independent of amyloid processing and can be induced by multiple ‘hits’ on vital neuronal functions. Type 2 diabetes (T2D) poses the most important risk factor for developing AD after ageing and dysfunctional IR/PI3K/Akt signalling is a major contributor in both diseases. We developed a model of T2D, coupling subdiabetogenic doses of streptozotocin (STZ) with a human junk food (HJF) diet to more closely mimic the human condition. Over 35 weeks, this induced classic signs of T2D (hyperglycemia ...
Source: Molecular Neurobiology - January 25, 2019 Category: Neurology Source Type: research

NeuroMuscleDB: a Database of Genes Associated with Muscle Development, Neuromuscular Diseases, Ageing, and Neurodegeneration
AbstractSkeletal muscle is a highly complex, heterogeneous tissue that serves a multitude of biological functions in living organisms. With the advent of methods, such as microarrays, transcriptome analysis, and proteomics, studies have been performed at the genome level to gain insight of changes in the expression profiles of genes during different stages of muscle development and of associated diseases. In the present study, a database was conceived for the straightforward retrieval of information on genes involved in skeletal muscle formation, neuromuscular diseases (NMDs), ageing, and neurodegenerative disorders (NDs)....
Source: Molecular Neurobiology - January 25, 2019 Category: Neurology Source Type: research

Molecular Insights into NR4A2(Nurr1): an Emerging Target for Neuroprotective Therapy Against Neuroinflammation and Neuronal Cell Death
AbstractNR4A2 is a nuclear receptor and a transcription factor, with distinctive physiological features. In the cell nuclei of the central nervous system, it is widely expressed and identified as a crucial regulator of dopaminergic (DA) neuronal differentiation, survival, and maintenance. Importantly, it has regulated different genes crucial for dopaminergic signals, and its expression has been diminished in both aged and PD post-mortem brains and reduced in PD patients. In microglia and astrocytes, the expression of NR4A2 has been found where it can be capable of inhibiting the expression of proinflammatory mediators; hen...
Source: Molecular Neurobiology - January 25, 2019 Category: Neurology Source Type: research

Metabo-lipidomics of Fibroblasts and Mitochondrial-Endoplasmic Reticulum Extracts from ALS Patients Shows Alterations in Purine, Pyrimidine, Energetic, and Phospholipid Metabolisms
AbstractAmyotrophic lateral sclerosis (ALS) is characterized by a wide metabolic remodeling, as shown by recent metabolomics and lipidomics studies performed in samples from patient cohorts and experimental animal models. Here, we explored the metabolome and lipidome of fibroblasts from sporadic ALS patients (n = 13) comparatively to age- and sex-matched controls (n = 11), and the subcellular fraction containing the mitochondria and endoplasmic reticulum (mito-ER), given that mitochondrial dysfunctions and ER stress are important features of ALS patho-mechanisms. We also assessed the mitochondri...
Source: Molecular Neurobiology - January 24, 2019 Category: Neurology Source Type: research

SNAP-25 in Serum Is Carried by Exosomes of Neuronal Origin and Is a Potential Biomarker of Alzheimer ’s Disease
AbstractA loss of synaptic density and connectivity is observed in multiple brain regions of Alzheimer ’s disease (AD) patients, resulting in a reduced expression of synaptic proteins such as SNAP-25 (synaptosomal-associated-protein-25). SNAP-25 alterations thus could be an index of the degree of synaptic degeneration in the central nervous system (CNS). We isolated from serum of both AD patients a nd healthy controls (HC) a population of neuron-derived exosomes (NDEs) and measured the concentrations of SNAP-25 contained in such NDEs. The levels of SNAP-25 carried by NDEs were reduced in AD patients (mean 459.05 ...
Source: Molecular Neurobiology - January 24, 2019 Category: Neurology Source Type: research

FABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation
In this study, we sought to examine the role of FABP7 in primary mouse astrocytes, focusing on its protective effect against reactive oxygen species (ROS) stress. In FABP7 knockout (KO) astrocytes, ROS induction significantly decreased LD accumulation, elevated ROS toxicity, and impaired thioredoxin (TRX) but not peroxiredoxin 1 (PRX1) signalling compared to ROS induction in wild-type astrocytes. Consequently, activation of apoptosis signalling molecules, including p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and increased expression of cleaved caspase ...
Source: Molecular Neurobiology - January 24, 2019 Category: Neurology Source Type: research

Exploring Cerebrospinal Fluid IgG N -Glycosylation as Potential Biomarker for Amyotrophic Lateral Sclerosis
AbstractAmyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease for which the existing candidate biomarkers (neurofilaments) have low specificity. Changes in blood IgGN-glycosylation have been observed in several diseases, including ALS, whereas cerebrospinal fluid (CSF) IgG has been less studied. Here, we characterizedN-glycans of CSF IgG from ALS patients in comparison with a control group of other neurological diseases. Cerebrospinal fluid was collected from patients with ALS (n = 26) and other neurological diseases (n = 10).N-Glycans were released from CSF purified IgG with pepti...
Source: Molecular Neurobiology - January 23, 2019 Category: Neurology Source Type: research

Non-Peptidergic Nociceptive Neurons Are Essential for Mechanical Inflammatory Hypersensitivity in Mice
AbstractSmall nerve fibers that bind the isolectin B4 (IB4+ C-fibers) are a subpopulation of primary afferent neurons that are involved in nociceptive sensory transduction and do not express the neuropeptides substance P and calcitonin-gene related peptide (CGRP). Several studies have attempted to elucidate the functional role of IB4+-nociceptors in different models of pain. However, a functional characterization of the non-peptidergic nociceptors in mediating mechanical inflammatory hypersensitivity in mice is still lacking. To this end, in the present study, the neurotoxin IB4-Saporin (IB4-Sap) was employed to ablate non...
Source: Molecular Neurobiology - January 23, 2019 Category: Neurology Source Type: research

Ethanol Exposure Transiently Elevates but Persistently Inhibits Tyrosine Kinase Activity and Impairs the Growth of the Nascent Apical Dendrite
In this study, we find that 10  min of alcohol exposure (400 mg/dL ethanol) by itself causes an unexpected increase in tyrosine phosphorylation of many proteins including Src and Dab1 that are essential downstream effectors of Reelin signaling. This increase in phosphotyrosine is dose-dependent and blockable by selective inhibi tors of Src Family Kinases (SFKs). However, the response is transient, and phosphotyrosine levels return to baseline after 30 min of continuous ethanol exposure, both in vitro and in vivo. During this latter period, Src is inactivated and Reelin application cannot stimulate Dab1 phosp...
Source: Molecular Neurobiology - January 23, 2019 Category: Neurology Source Type: research