Heme Oxygenase-1 and Carbon Monoxide Regulate Growth and Progression in Glioblastoma Cells
In conclusion, our data suggest that HO-1 and its by-product CO exhibit a cell-specific effect on various aspe cts of disease progression and are associated with a complex series of molecular mechanisms driving cell proliferation, survival and metastasis. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 27, 2020 Category: Neurology Source Type: research

Nociception in a Progressive Multiple Sclerosis Model in Mice Is Dependent on Spinal TRPA1 Channel Activation
In conclusion, these results support the hypothesis of the TRPA1 receptor involvement in nociception observed in a PMS-EAE model in mice. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 24, 2020 Category: Neurology Source Type: research

Correction to: Increased DNA Damage and Apoptosis in CDKL5-Deficient Neurons
The original version of this article unfortunately contained error in Fig.  5a to where a panel is missing. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 17, 2020 Category: Neurology Source Type: research

Context-Dependent Functions of E2F1: Cell Cycle, Cell Death, and DNA Damage Repair in Cortical Neurons
In this study, we investigate how DNA damage elicited by exposure to the topoisomerase I inhibitor camptothecin (CPT) leads to cycle-related death of cultu red cortical neurons and examine the function of E2F1 in this process. CPT treatment induced cell cycle initiation of cortical neurons and elevated the expression of certain cell cycle components (e.g., cyclin D1, CDK4, E2F1) but failed to drive S phase entry or DNA synthesis. The arrest in the cell cycle is explained by the elevated expression of the CDK inhibitor p21Cip1. Though its level was increased after CPT treatment, E2F1 did not drive treated neurons into the G...
Source: Molecular Neurobiology - February 15, 2020 Category: Neurology Source Type: research

Current and Future Therapies for Psoriasis with a Focus on Serotonergic Drugs
AbstractPsoriasis is a chronic immune-mediated skin disease, with a pathogenesis resulting from a combination of genetic and environmental factors. The pathogenesis of psoriasis is driven by the interaction between innate and adaptive immune cells and keratinocytes, in a complex process mediated by cytokines and other signaling molecules. This leads to an inflammatory process with increased proliferation of epidermal cells, neo-angiogenesis, and infiltration of white cells in the skin, which cause the characteristic psoriasis plaques. Several studies have suggested that the neurotransmitter serotonin, a key mediator betwee...
Source: Molecular Neurobiology - February 15, 2020 Category: Neurology Source Type: research

Genetic Up-Regulation or Pharmacological Activation of the Na + /Ca 2+ Exchanger 1 (NCX1) Enhances Hippocampal-Dependent Contextual and Spatial Learning and Memory
AbstractThe Na+/Ca2+ exchanger 1 (NCX1) participates in the maintenance of neuronal Na+ and Ca2+ homeostasis, and it is highly expressed at synapse level of some brain areas involved in learning and memory processes, including the hippocampus, cortex, and amygdala. Furthermore, NCX1 increases Akt1 phosphorylation and enhances glutamate-mediated Ca2+ influx during depolarization in hippocampal and cortical neurons, two processes involved in learning and memory mechanisms. We investigated whether the modulation of NCX1 expression/activity might influence learning and memory processes. To this aim, we used a knock-in mouse ov...
Source: Molecular Neurobiology - February 11, 2020 Category: Neurology Source Type: research

MicroRNA Regulatory Network as Biomarkers of Late Seizure in Patients with Spontaneous Intracerebral Hemorrhage
AbstractApproximately 15% of patients experience seizures after spontaneous intracerebral hemorrhage (ICH). The pathogenesis of seizures post-ICH is not well-known; however, iron deposition –related neuronal injury following hemoglobin breakdown may contribute. Profiling known miRNAs to identify biomarkers for post-ICH late seizures, we found 64 differentially expressed miRNA: 32 upregulated and 32 downregulated in seizure vs. non-seizure. Functional classification of upregulated miR NA for KEGG pathways and biological processes identified enrichment for cell cycle, protein modifications, and FoxO neurotrophin signal...
Source: Molecular Neurobiology - February 10, 2020 Category: Neurology Source Type: research

Increased Levels of Plasma Tumor Necrosis Factor- α Mediate Schizophrenia Symptom Dimensions and Neurocognitive Impairments and Are Inversely Associated with Natural IgM Directed to Malondialdehyde and Paraoxonase 1 Activity
AbstractAccumulating evidence suggests that TNF- α-mediated immune-neurotoxicity contributes to cognitive impairments and the overall severity of schizophrenia (OSOS). There are no data whether peripheral IL-6 and IL-4 may affect the phenome of schizophrenia above and beyond the effects of TNF-α and whether those cytokines are regulated by lower ed natural IgM to malondialdehyde (MDA) and paraoxonase 1 enzyme activity. We assessed the aforementioned biomarkers in a cross-sectional study that enrolled schizophrenia patients with (n = 40) and without (n = 40) deficit schizophrenia and ...
Source: Molecular Neurobiology - February 10, 2020 Category: Neurology Source Type: research

Oxidative Stress in Autism Spectrum Disorder
AbstractAccording to the United States Centers for Disease Control and Prevention (CDC), as of July 11, 2016, the reported average incidence of children diagnosed with an autism spectrum disorder (ASD) was 1 in 68 (1.46%) among 8-year-old children born in 2004 and living within the 11 monitoring sites ’ surveillance areas in the United States of America (USA) in 2012. ASD is a multifaceted neurodevelopmental disorder that is also considered a hidden disability, as, for the most part; there are no apparent morphological differences between children with ASD and typically developing children. ASD is diagnosed based upo...
Source: Molecular Neurobiology - February 5, 2020 Category: Neurology Source Type: research

Differential Expression of Hippocampal Circular RNAs in the BTBR Mouse Model for Autism Spectrum Disorder
In conclusion, our results indicate a consistent deregulation of circRNA expression in the hippocampus of BTBR mice. ASD-related circRNAs should be considered in functional studies to identify their contribution to the etiology of the disorder. In addition, as abundant and highly stable molecules, circRNAs represent interesting potential biomarkers for autism. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 4, 2020 Category: Neurology Source Type: research

BAX-Depleted Retinal Ganglion Cells Survive and Become Quiescent Following Optic Nerve Damage
In this study,Bax+/ − mice were used to test the hypothesis that lowering the quantity of BAX in RGCs would delay apoptosis following optic nerve injury. RGCs were damaged by performing optic nerve crush (ONC) and then immunostaining for phospho-cJUN, and quantitative PCR were used to monitor the status of the BAX activation mechanism in the months following injury. The apoptotic susceptibility of injured cells was directly tested by virally introducing GFP-BAX intoBax−/− RGCs after injury. The competency of quiescent RGCs to reactivate their BAX activation mechanism was tested by intravitreal injection o...
Source: Molecular Neurobiology - February 1, 2020 Category: Neurology Source Type: research

The Expression of CNS-Specific PPARGC1A Transcripts Is Regulated by Hypoxia and a Variable GT Repeat Polymorphism
AbstractPPARGC1A encodes a transcriptional co-activator also termed peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1-alpha (PGC-1 α) which orchestrates multiple transcriptional programs. We have recently identified CNS-specific transcripts that are initiated far upstream of the reference gene (RG) promoter. The regulation of these isoforms may be relevant, as experimental and genetic studies implicated thePPARGC1A locus in neurodegenerative diseases. We therefore studied cis- and trans-regulatory elements activating the CNS promoter in comparison to the RG promoter in human neuronal cell lines. A...
Source: Molecular Neurobiology - February 1, 2020 Category: Neurology Source Type: research

Mesenchymal Stem Cells Therapy Improved the Streptozotocin-Induced Behavioral and Hippocampal Impairment in Rats
In this study, we hypothesized that long-lasting therapy with mesench ymal stem cells (MSC) would have a restorative effect on the behavioral alterations and cognitive decline typical of sAD, as they have shown neurogenic and immunomodulatory activities. To test this, we chronically injected intravenous human MSC in a sAD rat model induced by the intracerebroventricul ar injection of streptozotocin (STZ). During the last 2 weeks, we performed open field, Barnes maze, and marble burying tests. STZ-treated rats displayed a poor performance in all behavioral tests. Cell therapy increased exploratory behavior, decreased a...
Source: Molecular Neurobiology - February 1, 2020 Category: Neurology Source Type: research

GLUT12 Expression in Brain of Mouse Models of Alzheimer ’s Disease
AbstractThe brain depends on glucose as a source of energy. This implies the presence of glucose transporters, being GLUT1 and GLUT3 the most relevant. Expression of GLUT12 is found in mouse and human brain at low levels. We previously demonstrated GLUT12 upregulation in the frontal cortex of aged subjects that was even higher in aged Alzheimer ’s disease (AD) patients. However, the cause and the mechanism through which this increase occurs are still unknown. Here, we aimed to investigate whether the upregulation of GLUT12 in AD is related with aging or Aβ deposition in comparison with GLUT1, GLUT3, and GLUT4. I...
Source: Molecular Neurobiology - February 1, 2020 Category: Neurology Source Type: research

The N-Terminal Polybasic Region of Prion Protein Is Crucial in Prion Pathogenesis Independently of the Octapeptide Repeat Region
AbstractConformational conversion of the cellular isoform of prion protein, designated PrPC, into the abnormally folded, amyloidogenic isoform, PrPSc, is an essential pathogenic event in prion diseases. However, the exact conversion mechanism remains largely unknown. Lines of evidence indicate that the N-terminal domain, which includes the N-terminal, positively charged polybasic region and the octapeptide repeat (OR) region, is important for PrPC to convert into PrPSc after infection with prions. To further gain insights into the role of the polybasic region and the OR region in prion pathogenesis, we generated two differ...
Source: Molecular Neurobiology - February 1, 2020 Category: Neurology Source Type: research

Phosphodiesterase 7 Regulation in Cellular and Rodent Models of Parkinson ’s Disease
AbstractParkinson ’s disease is characterized by a loss of dopaminergic neurons in the ventral midbrain. This disease is diagnosed when around 50% of these neurons have already died; consequently, therapeutic treatments start too late. Therefore, an urgent need exists to find new targets involved in the onset and p rogression of the disease. Phosphodiesterase 7 (PDE7) is a key enzyme involved in the degradation of intracellular levels of cyclic adenosine 3′, 5′-monophosphate in different cell types; however, little is known regarding its role in neurodegenerative diseases, and specifically in Parkinson&rs...
Source: Molecular Neurobiology - February 1, 2020 Category: Neurology Source Type: research

Cell-Type-Specific Analysis of Molecular Pathology in Autism Identifies Common Genes and Pathways Affected Across Neocortical Regions
AbstractDespite its heterogeneity, autism is characterized by a defined behavioral phenotype, suggesting that the molecular pathology affects specific neural substrates to cause behavioral dysfunction. Previous studies identified genes dysregulated in autism cortex but did not address their cell-type specificity. Moreover, it is unknown whether there is a core of genes dysregulated across multiple neocortical regions. We applied RNA sequencing to postmortem brain tissue samples from autism patients and neurologically normal controls and combined our data with previously published datasets. We then identified genes, pathway...
Source: Molecular Neurobiology - February 1, 2020 Category: Neurology Source Type: research

Amyloid Fibril –Induced Astrocytic Glutamate Transporter Disruption Contributes to Complement C1q-Mediated Microglial Pruning of Glutamatergic Synapses
AbstractThe complement C1q plays a critical role in microglial phagocytosis of glutamatergic synapses and in the pathogenesis of neuroinflammation in Alzheimer ’s disease (AD). We recently reported that upregulation of metabotropic glutamate receptor signaling is associated with increased synaptic C1q production and subsequent microglial phagocytosis of synapses in the rodent models of AD. Here, we explored the role of astrocytic glutamate transporter in the synaptic C1q production and microglial phagocytosis of hippocampal glutamatergic synapses in a rat model of AD. Activation of astrocyte and reduction glutamate t...
Source: Molecular Neurobiology - February 1, 2020 Category: Neurology Source Type: research

The Anti-Neuron-Specific Enolase Antibody Induced Neuronal Cell Death in a Novel Fashion
AbstractSuppression of ubiquitin proteasome pathway (UPP) and stimulation of caspase-3 are involved in neurodegeneration. Can UPP activators and caspase-3 inhibitors ameliorate neurodegeneration? Here, we found a novel neuronal cell death accompanied with UPP activation and caspase-3 inhibition. Recently, plasmalemmal neuron-specific enolase (NSE) has been identified as one of membrane targets of 15-deoxy- Δ12,14-prostaglandin J2 (15d-PGJ2). 15d-PGJ2 induces neuronal apoptosis via activating caspase-3 and inactivating UPP, whereas the anti-NSE antibody inactivated caspase-3, activated UPP, and caused neuronal cell de...
Source: Molecular Neurobiology - January 31, 2020 Category: Neurology Source Type: research

Correction to: Ancestral Folate Promotes Neuronal Regeneration in Serial Generations of Progeny
The original version of this article unfortunately contained error in Figure 4a to where some of the text was overlapping. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - January 30, 2020 Category: Neurology Source Type: research

Increased DNA Damage and Apoptosis in CDKL5-Deficient Neurons
AbstractMutations in theCDKL5 gene, which encodes a serine/threonine kinase, causes a rare encephalopathy, characterized by early-onset epilepsy and severe intellectual disability, named CDKL5 deficiency disorder (CDD). In vitro and in vivo studies in mouse models of Cdkl5 deficiency have highlighted the role of CDKL5 in brain development and, in particular, in the morphogenesis and synaptic connectivity of hippocampal and cortical neurons. Interestingly, Cdkl5 deficiency in mice increases vulnerability to excitotoxic stress in hippocampal neurons. However, the mechanism by which CDKL5 controls neuronal survival is far fro...
Source: Molecular Neurobiology - January 30, 2020 Category: Neurology Source Type: research

Selected microRNAs Increase Synaptic Resilience to the Damaging Binding of the Alzheimer ’s Disease Amyloid Beta Oligomers
AbstractAlzheimer ’s disease (AD) is marked by synaptic loss (at early stages) and neuronal death (at late stages). Amyloid beta (Aβ) and tau oligomers can target and disrupt synapses thus driving cognitive decay. Non-demented individuals with Alzheimer’s neuropathology (NDAN) are capable of withstanding Aβ and tau toxicity, thus remaining cognitively intact despite presence of AD neuropathology. Understanding the involved mechanism(s) would lead to development of novel effective therapeutic strategies aimed at promoting synaptic resilience to amyloid toxicity. NDAN have a unique hippocampal post-syna...
Source: Molecular Neurobiology - January 29, 2020 Category: Neurology Source Type: research

Regulation of Small GTPase Prenylation in the Nervous System
AbstractMevalonate pathway inhibitors have been extensively studied for their roles in cholesterol depletion and for inhibiting the prenylation and activation of various proteins. Inhibition of protein prenylation has potential therapeutic uses against neurological disorders, like neural cancers, neurodegeneration, and neurotramatic lesions. Protection against neurodegeneration and promotion of neuronal regeneration is regulated in large part by Ras superfamily small guanosine triphosphatases (GTPases), particularly the Ras, Rho, and Rab subfamilies. These proteins are prenylated to target them to cellular membranes. Preny...
Source: Molecular Neurobiology - January 27, 2020 Category: Neurology Source Type: research

Sephin1 Reduces Prion Infection in Prion-Infected Cells and Animal Model
AbstractPrion diseases are fatal infectious neurodegenerative disorders in human and animals caused by misfolding of the cellular prion protein (PrPC) into the infectious isoform PrPSc. These diseases have the potential to transmit within or between species, and no cure is available to date. Targeting the unfolded protein response (UPR) as an anti-prion therapeutic approach has been widely reported for prion diseases. Here, we describe the anti-prion effect of the chemical compound Sephin1 which has been shown to protect in mouse models of protein misfolding diseases including amyotrophic lateral sclerosis (ALS) and multip...
Source: Molecular Neurobiology - January 24, 2020 Category: Neurology Source Type: research

Defining a Time Window for Neuroprotection and Glia Modulation by Caffeine After Neonatal Hypoxia-Ischaemia
In conclusion, caffeine only yielded neuroprotection and immunomodulation in a neonatal model of brain hypoxia ischaemia if administered immediately after injury. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - January 23, 2020 Category: Neurology Source Type: research

The Ubiquitin System: a Regulatory Hub for Intellectual Disability and Autism Spectrum Disorder
AbstractIntellectual disability (ID) and autism spectrum disorder (ASD) are two of the most common neurodevelopmental disorders. Both disorders are extremely heterogenous, and only ~  40% of reported cases have so far been attributed to genetic mutations. Of the many cellular processes that are affected, the ubiquitin system (UbS) is of particular relevance in that it can rapidly regulate multiple signaling cascades simultaneously. The UbS is a post-translational modification process that revolves around the covalent attachment of a ubiquitin moiety to a substrate, thereby influencing different elements of protein b...
Source: Molecular Neurobiology - January 23, 2020 Category: Neurology Source Type: research

Retraction Note: Aluminum in Neurological and Neurodegenerative Disease
The Editor-in Chief of Molecular Neurobiology has retracted this article [1] at the request of the corresponding author. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - January 23, 2020 Category: Neurology Source Type: research

Antioxidant and Anti-inflammatory Diagnostic Biomarkers in Multiple Sclerosis: A Machine Learning Study
AbstractAn imbalance of inflammatory/anti-inflammatory and oxidant/antioxidant molecules has been implicated in the demyelination and axonal damage in multiple sclerosis (MS). The current study aimed to evaluate the plasma levels of tumor necrosis factor (TNF)- α, soluble TNF receptor (sTNFR)1, sTNFR2, adiponectin, hydroperoxides, advanced oxidation protein products (AOPP), nitric oxide metabolites, total plasma antioxidant capacity using the total radical-trapping antioxidant parameter (TRAP), sulfhydryl (SH) groups, as well as serum levels of zinc in 17 4 MS patients and 182 controls. The results show that MS is ch...
Source: Molecular Neurobiology - January 22, 2020 Category: Neurology Source Type: research

Comparative Pro-cognitive and Neurochemical Profiles of Glycine Modulatory Site Agonists and Glycine Reuptake Inhibitors in the Rat: Potential Relevance to Cognitive Dysfunction and Its Management
In conclusion, despite contrasting neurochemical profiles, partial glycine site agonists and glycine reuptake inhibitors exhibit comparable pro-cognitive effects in rats of poten tial relevance to treatment of schizophrenia and other brain disorders where cognitive performance is impaired. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - January 20, 2020 Category: Neurology Source Type: research

Reduced Influence of apoE on A β43 Aggregation and Reduced Vascular Aβ43 Toxicity as Compared with Aβ40 and Aβ42
AbstractThe amyloid- β 43 (Aβ43) peptide has been shown to be abundantly expressed in Alzheimer’s disease plaques, whereas only relatively low levels have been demonstrated in cerebral amyloid angiopathy (CAA). To better understand this discrepant distribution, we studied various biochemical properties of Aβ43, in comparison with Aβ40 and Aβ42. We assessed the interaction of Aβ43 with the three apoE isoforms (apoE2, apoE3, and apoE4) using SDS-PAGE/Western blotting and ELISA, aggregation propensity using thioflavin T assays, and cytotoxicity towards cerebrovascular cells using MTT assays...
Source: Molecular Neurobiology - January 17, 2020 Category: Neurology Source Type: research

A Homeobox Transcription Factor Scarecrow (SCRO) Negatively Regulates Pdf Neuropeptide Expression through Binding an Identified cis -Acting Element in Drosophila melanogaster
AbstractInDrosophila, transcriptional feedback loops contribute to intracellular timekeeping mechanisms responsible for daily rhythms. Pigment-dispersing factor (PDF) is the major neuropeptide produced by latero-ventral neurons (LNvs) that function as a central pacemaker for circadian locomotor activity rhythms. PDF synchronizes other clock neurons thereby playing an essential role in the maintenance and coordination of circadian locomotor rhythms. However, the underlying molecular mechanism of the LNvs-specificPdf expression is not well understood. Here, usingPdf promoter-bashing experiment, we identified acis-actingPdf r...
Source: Molecular Neurobiology - January 16, 2020 Category: Neurology Source Type: research

Correction to: Progerin-Induced Transcriptional Changes in Huntington ’s Disease Human Pluripotent Stem Cell-Derived Neurons
In the original version of the paper, the name of one of the contributing authors, Dr. Mundackal S. Divya (orcid:0000-0002-2869-7191). (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - January 15, 2020 Category: Neurology Source Type: research

Pituitary Adenylate Cyclase-Activating Polypeptide in the Ventromedial Hypothalamus Is Responsible for Food Intake Behavior by Modulating the Expression of Agouti-Related Peptide in Mice
AbstractPituitary adenylate cyclase-activating polypeptide (PACAP) is abundantly expressed in the hypothalamus and contributes to hypothalamic functions, including appetite regulation. Although food intake is suggested to be decreased in PACAP ( −/−) mice, the detailed mechanisms are still being discussed. We sought to investigate this link. The food consumption at 8 h after refeeding in the (−/−) mice who had fasted for 2 days was significantly lower than in the PACAP (+/+) mice. The nocturnal and daily food intake of (−/−) m ice was significantly lower than those of (+/+) mic...
Source: Molecular Neurobiology - January 11, 2020 Category: Neurology Source Type: research

CRISPR, Prime Editing, Optogenetics, and DREADDs: New Therapeutic Approaches Provided by Emerging Technologies in the Treatment of Spinal Cord Injury
AbstractSpinal cord injury (SCI) causes temporary disabilities or permanent effects including neuropathic pain and spastiscity. The damage often results frommechanical trauma, which in turn triggers the neuroinflammatory process. Neuroinflammation plays essential roles in the structural, biochemical, and cellular changes that take place in the spinal cord after the injury. Indeed, SCI activates many different signaling pathways that coordinate the resulting cellular responses. While neuroinflammation serves as a physiological reaction to harmful stimuli, it is clear that long-lasting inflammatory response leads to aggravat...
Source: Molecular Neurobiology - January 11, 2020 Category: Neurology Source Type: research

Neuroendocrine Effects of Lactation and Hormone-Gene-Environment Interactions
AbstractWhile correlational studies suggest that lactation may confer a certain level of protection from mental illness, this benefit is not uniformly expressed in all women who choose to breastfeed. We propose here that the neuroendocrine “resetting” induced by lactation may predispose toward positive affect states in a subset of hormone-sensitive mothers, with hormone-gene and hormone-environment interactions determining the ultimate psychological outcome. We find evidence to suggest that higher secretion of prolactin/oxytocin a s well as lower secretion of vasopression/androgens in lactating mothers may prot...
Source: Molecular Neurobiology - January 11, 2020 Category: Neurology Source Type: research

Ancestral Folate Promotes Neuronal Regeneration in Serial Generations of Progeny
AbstractFolate supplementation in F0 mating rodents increases regeneration of injured spinal axons in vivo in 4 or more generations of progeny (F1 –F4) in the absence of interval folate administration to the progeny. Transmission of the enhanced regeneration phenotype to untreated progeny parallels axonal growth in neuron culture after in vivo folate administration to the F0 ancestors alone, in correlation with differential patterns of genom ic DNA methylation and RNA transcription in treated lineages. Enhanced axonal regeneration phenotypes are observed with diverse folate preparations and routes of administration, ...
Source: Molecular Neurobiology - January 10, 2020 Category: Neurology Source Type: research

Lactate: More Than Merely a Metabolic Waste Product in the Inner Retina
AbstractThe retina is an extension of the central nervous system and has been considered to be a simplified, more tractable and accessible version of the brain for a variety of neuroscience investigations. The optic nerve displays changes in response to underlying neurodegenerative diseases, such as stroke, multiple sclerosis, and Alzheimer ’s disease, as well as inner retinal neurodegenerative disease, e.g., glaucoma. Neurodegeneration has increasingly been linked to dysfunctional energy metabolism or conditions in which the energy supply does not meet the demand. Likewise, increasing lactate levels have been correl...
Source: Molecular Neurobiology - January 8, 2020 Category: Neurology Source Type: research

Cellular and Molecular Changes in Hippocampal Glutamate Signaling and Alterations in Learning, Attention, and Impulsivity Following Prenatal Nicotine Exposure
AbstractOver 70 million European pregnant women are smokers during their child-bearing years. Consumption of tobacco-containing products during pregnancy is associated with several negative behavioral outcomes for the offspring, including a higher susceptibility for the development of attention-deficit/hyperactive disorder (ADHD). In efforts to minimize fetal exposure to tobacco smoke, many women around the world switch to nicotine replacement therapies (NRTs) during the gestational period; however, prenatal nicotine exposure (PNE) in any form has been associated with alterations in cognitive processes, including learning,...
Source: Molecular Neurobiology - January 8, 2020 Category: Neurology Source Type: research

Elevated Type 1 Metabotropic Glutamate Receptor Availability in a Mouse Model of Huntington ’s Disease: a Longitudinal PET Study
In this study, we assessed in vivo pathological changes in mGluR1 availability in the Q175DN mouse model of HD using longitudinal positron emission tomography (PET) imaging with the radioligand [11C]ITDM. Ninety-minute dynamic PET imaging scans were performed in 22 heterozygous (HET) Q175DN mice and 22 wild-type (WT) littermates longitudinally at 6, 12, and 16  months of age. Analyses of regional volume of distribution with an image-derived input function (VT (IDIF)) and voxel-wise parametricVT (IDIF) maps were performed to assess differences between genotypes.Post-mortem evaluation at 16  months was done to supp...
Source: Molecular Neurobiology - January 8, 2020 Category: Neurology Source Type: research

Intracerebral Expression of AAV-APOE4 Is Not Sufficient to Alter Tau Burden in Two Distinct Models of Tauopathy
AbstractApolipoprotein E4 (APOE4) is the major genetic risk factor for sporadic Alzheimer's disease (AD), which is characterized by amyloid β (Aβ) plaques and tau tangles. Though the role of APOE4 in Aβ pathogenesis has been mechanistically defined in rodent models, much less is known regarding the relationship of APOE4 to tau pathogenesis. Recent studies have indicated a possible correlation between APOE isoform-dependent alteratio ns in tau pathology and neurodegeneration. To explore whether neuronal expression of APOE4 triggers tauopathy, here we delivered adeno-associated viruses (AAV) expressing hu...
Source: Molecular Neurobiology - January 6, 2020 Category: Neurology Source Type: research

Comparison of Effects of Spatial and Non-Spatial Memory Acquisition on the CaMKII Pathway During Hypothyroidism and Nicotine Treatment
AbstractMolecular, cellular, and behavioral studies have shown that hypothyroidism impairs hippocampus-dependent learning and memory in adult rats. In these studies, spatial learning and memory were tested in the radial arm water maze (RAWM), which involved locating a hidden platform. In the present study, we investigated the effects of nicotine and hypothyroidism on the CaMKII pathway during learning and memory processes in both spatial and non-spatial memory forms. We used nicotine as a neuroprotective agent. Hypothyroidism was induced by thyroidectomy in adult rats. Rats were trained on the hidden platform (the RAWM for...
Source: Molecular Neurobiology - January 3, 2020 Category: Neurology Source Type: research

Targeting Cannabinoid Receptor Activation and BACE-1 Activity Counteracts TgAPP Mice Memory Impairment and Alzheimer ’s Disease Lymphoblast Alterations
We report here that NP137 and NP148 showed neuroprotective effects in amyloid-β-treated primary cortical neurons, and NP137 in particu lar rescued the cognitive deficit of TgAPP mice. The latter compound was able to blunt the abnormal cell response to serum addition or withdrawal of lymphoblasts derived from AD patients. It is suggested that NP137 could be a good drug candidate for future treatment of AD. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - January 3, 2020 Category: Neurology Source Type: research

Alzheimer ’s Disease and Diabetes: Insulin Signaling as the Bridge Linking Two Pathologies
AbstractAlzheimer ’s (or Alzheimer) disease (AD) is the most prevalent subset of dementia, affecting elderly populations worldwide. The cumulative costs of the AD care are rapidly accelerating as the average lifespan increases. Onset and risk factors for AD and AD-like dementias have been largely unknown until rece ntly. Studies show that chronic type II diabetes mellitus (DM) is closely associated with neurodegeneration, especially AD. Type II DM is characterized by the cells’ inability to take up insulin, as well as chronic hyperglycemia. In the central nervous system, insulin has crucial regulatory roles, wh...
Source: Molecular Neurobiology - January 3, 2020 Category: Neurology Source Type: research

Promising Role of Nano-Encapsulated Drugs for Spinal Cord Injury
AbstractNanomaterials have been utilized for the drug delivery in the central nervous system (CNS), and many research investigators are currently focussing on this specified area. There has been a lot of advancement in the nanoparticle-mediated drug delivery to the brain. Neuronal injuries including spinal cord injury (SCI) and their targeted therapies are still in its infancy on this planet. SCI has been known to cause axonal damage followed by the loss of communication between CNS and other non-neuronal systems. SCI has been critically associated with prolonged inflammation, sensory dysfunction, and motor impairment in S...
Source: Molecular Neurobiology - January 3, 2020 Category: Neurology Source Type: research

Gene Therapy with Single-Subunit Yeast NADH-Ubiquinone Oxidoreductase (NDI1) Improves the Visual Function in Experimental Autoimmune Encephalomyelitis (EAE) Mice Model of Multiple Sclerosis (MS)
In conclusion, targeting the dysfunctional complex I usingNDI1 gene can be an approach to address axonal and neuronal loss responsible for permanent disability in MS that is unaltered by current disease modifying drugs. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - January 3, 2020 Category: Neurology Source Type: research

P2X4 Receptors on Muscle Macrophages Are Required for Development of Hyperalgesia in an Animal Model of Activity-Induced Muscle Pain
AbstractActivity-induced pain is common in those with chronic musculoskeletal pain and limits participation in daily activities and exercise. Our laboratory developed a model of activity-induced pain and shows that depletion of muscle macrophages prevents development of hyperalgesia. Adenosine triphosphate (ATP) is released from fatiguing muscle and activates purinergic receptors (P2X), and P2X4 receptors are expressed on macrophages. We hypothesized that exercise releases ATP to activate P2X4 receptors on muscle macrophages, which subsequently release interleukin-1 β (IL-1β) to produce hyperalgesia. In an animal...
Source: Molecular Neurobiology - January 2, 2020 Category: Neurology Source Type: research

Correction to: NMDA Receptors Regulate Neuregulin 2 Binding to ER-PM Junctions and Ectodomain Release by ADAM10
The original version of this article unfortunately contained an error in Title as the authors inadvertently deleted during revisions the last two words of the  paper’s title (“by ADAM10”), which is very important for explaining the article’s content and impact. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - January 1, 2020 Category: Neurology Source Type: research

Phenotypic Characterization of Larval Zebrafish ( Danio rerio ) with Partial Knockdown of the cacna1a Gene
In this study, we aimed for the first time to assess phenotypic and behavioral alterations in larval zebrafish with partialcacna1aa knockdown, placing special emphasis on changes in epileptiform-like electrographic discharges in larval brains. Whole-mount in situ hybridization analysis revealed expression ofcacna1aa in the optic tectum and medulla oblongata of larval zebrafish at 4 and 5  days post-fertilization. Next, microinjection of two antisense morpholino oligomers (individually or in combination) targeting all splice variants ofcacna1aa into fertilized zebrafish eggs resulted in dose-dependent mortality and dec...
Source: Molecular Neurobiology - December 26, 2019 Category: Neurology Source Type: research

Neuroprotective Effects of Doxycycline in the R6/2 Mouse Model of Huntington ’s Disease
AbstractMechanisms of tissue damage in Huntington ’s disease involve excitotoxicity, mitochondrial damage, and inflammation, including microglia activation. Immunomodulatory and anti-protein aggregation properties of tetracyclines were demonstrated in several disease models. In the present study, the neuroprotective and anti-inflammatory effects of the tetracycline doxycycline were investigated in the mouse model of HD disease R6/2. Transgenic mice were daily treated with doxycycline 20 mg/kg, starting from 4 weeks of age. After sacrifice, histological and immunohistochemical studies were performed. We foun...
Source: Molecular Neurobiology - December 26, 2019 Category: Neurology Source Type: research

Preferential Neurodegeneration in the Dentate Gyrus by Amyloid β 1–42 -Induced Intracellular Zn 2+ Dysregulation and Its Defense Strategy
AbstractOn the basis of the evidence that rapid intracellular Zn2+ dysregulation by amyloid β1 –42 (A β1 –42) in the normal hippocampus transiently induces cognitive decline, here we report preferential neurodegeneration in the dentate gyrus by A β1 –42-induced intracellular Zn2+ dysregulation and its defense strategy. Neurodegeneration was preferentially observed in the dentate granule cell layer in the hippocampus after a single A β1 –42 injection into the lateral ventricle but not in the CA1 and CA3 pyramidal cell layers, while intracellular Zn2+ dysregulation was extensively ...
Source: Molecular Neurobiology - December 21, 2019 Category: Neurology Source Type: research