Correction to: Cotinine: A Therapy for Memory Extinction in Post-traumatic Stress Disorder
The original version of this article unfortunately contained mistake in its Funding inforation. That is, the Grant Number has an error currently read as “This work was supported by the Fondo de Ciencia y Tecnología (FONDECYT) de Chile, Grant #1150149”. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - July 20, 2018 Category: Neurology Source Type: research

IVIG Delays Onset in a Mouse Model of Gerstmann-Str äussler-Scheinker Disease
In this study, we used Gerstmann-Sträussler-Scheinker (GSS)-Tg (PrP-A116V) transgenic mice to test IVIG efficacy since amyloid plaque formation played an important role in GSS pathogenesis. H ere, we provided strong evidence that demonstrates how IVIG could significantly delay disease onset, elongate survival, and improve clinical phenotype in Tg (PrP-A116V) mice. Additionally, in treated animals, IVIG could markedly inhibit PrP amyloid plaque formation and attenuate neuronal apoptosis a t the age of 120 days in mice. Our results indicate that IVIG may be a potential, effective therapeutic treatment for GSS and o...
Source: Molecular Neurobiology - July 19, 2018 Category: Neurology Source Type: research

Recombinant FGF21 Protects Against Blood-Brain Barrier Leakage Through Nrf2 Upregulation in Type 2 Diabetes Mice
This study may provide an impetus for development of therapeutics targeting BBB damage in diabetes. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - July 19, 2018 Category: Neurology Source Type: research

Resveratrol as a Therapy to Restore Neurogliogenesis of Neural Progenitor Cells Infected by Toxoplasma gondii
AbstractThe intracellular protozoanToxoplasma gondii may cause congenital toxoplasmosis and serious brain damage in fetus. However, the underlying mechanism of neuropathogenesis in brain toxoplasmosis remains unclear. For this study, neural progenitor cells (NPCs) were obtained from embryo telencephalons (embryonic day 13) and induced to proliferation in the presence of growth factors (GFs). For gathering insights into the biological effects of resveratrol (RSV) on neurogenesis, this study aimed to investigate effects of RSV concentrations (0.1 to 100  μM) on proliferation, migration and differentiation of NPCs inf...
Source: Molecular Neurobiology - July 19, 2018 Category: Neurology Source Type: research

Correction to: Growth Factors and Neuroglobin in Astrocyte Protection Against Neurodegeneration and Oxidative Stress
The original version of this article unfortunately contained a typo error. The name of author “Ghulam Md Ashrad” should be written as “Ghulam Md Ashraf”. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - July 19, 2018 Category: Neurology Source Type: research

Dehydroepiandrosterone Induces Temozolomide Resistance Through Modulating Phosphorylation and Acetylation of Sp1 in Glioblastoma
AbstractGlioblastoma is the most malignant type of brain tumor for which there are currently no effective treatments. Patient prognosis is improved by radiation combined with temozolomide (TMZ) therapy but only for a short period of time due to the high prevalence of recurrence. Although O6-methylguanine-DNA methyltransferase (MGMT)-mediated DNA repair is a well-defined characteristic of TMZ resistance, the mechanism by which MGMT-deficient glioblastoma counteracts TMZ-induced DNA damage, leading to apoptosis, still remains unclear. Previously, we determined that aberrantly activated cytochrome P450 17A1 causes TMZ resista...
Source: Molecular Neurobiology - July 18, 2018 Category: Neurology Source Type: research

Stores, Channels, Glue, and Trees: Active Glial and Active Dendritic Physiology
AbstractGlial cells and neuronal dendrites were historically assumed to be passive structures that play only supportive physiological roles, with no active contribution to information processing in the central nervous system. Research spanning the past few decades has clearly established this assumption to be far from physiological realities. Whereas the discovery of active channel conductances and their localized plasticity was the turning point for dendritic structures, the demonstration that glial cells release transmitter molecules and communicate across the neuroglia syncytium through calcium wave propagation constitu...
Source: Molecular Neurobiology - July 16, 2018 Category: Neurology Source Type: research

Peripheral Biomarkers for Early Detection of Alzheimer ’s and Parkinson’s Diseases
This article reviews the peripheral biomarkers explored for early detection of Alzheimer’s and Parkinson’s diseases including blood cells, skin fibroblast, proteomics, saliva, olfactory, stomach and colon, heart and peripheral nervous system, and others.Graphical Abstractᅟ (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - July 14, 2018 Category: Neurology Source Type: research

Chemotherapy-Induced Cognitive Impairment Is Associated with Cytokine Dysregulation and Disruptions in Neuroplasticity
In this study, mice received three intraperitoneal injections of a combination of docetaxel, adriamycin, and cyclophosphamide (DAC) at 2-day intervals. A water maze test was used to examine cognitive performance, and manganese-enhanced magnetic resonance im aging (MEMRI) was used to examine hippocampal neuronal activity. The whole brain, prefrontal cortex, hippocampus, and blood samples were then collected for cytokine measurement. The DAC-treated mice displayed a significantly shorter duration spent in and fewer entries into the target quadrant of the water maze than the control mice and a pronounced decrease in MEMRI sig...
Source: Molecular Neurobiology - July 14, 2018 Category: Neurology Source Type: research

Pharmacological Sequestration of Mitochondrial Calcium Uptake Protects Neurons Against Glutamate Excitotoxicity
AbstractNeuronal excitotoxicity which is induced by exposure to excessive extracellular glutamate is shown to be involved in neuronal cell death in acute brain injury and a number of neurological diseases. High concentration of glutamate induces calcium deregulation which results in mitochondrial calcium overload and mitochondrial depolarization that triggers the mechanism of cell death. Inhibition of mitochondrial calcium uptake could be potentially neuroprotective but complete inhibition of mitochondrial calcium uniporter could result in the loss of some physiological processes linked to Ca2+ in mitochondria. Here, we fo...
Source: Molecular Neurobiology - July 14, 2018 Category: Neurology Source Type: research

Neonatal Dexamethasone Treatment Suppresses Hippocampal Estrogen Receptor α Expression in Adolescent Female Rats
AbstractPrevious studies showed that neonatal dexamethasone treatment (NDT) transiently impaired hippocampal function in male rats. Hippocampal estrogen receptors (ERs) participate in avoidance learning. As previous studies focused on males only, this study was aimed to investigate the NDT effects on the hippocampal function of female rats. Newborn Wistar female rats were subjected to a tapering dose of dexamethasone (0.5  mg, 0.3 mg, and 0.1 mg/kg, subcutaneously) from postnatal days 1 to 3 and were subjected to experiments at the age of 6 weeks (adolescence). Brain slice extracellular recording and th...
Source: Molecular Neurobiology - July 13, 2018 Category: Neurology Source Type: research

A β Oligomer Elimination Restores Cognition in Transgenic Alzheimer’s Mice with Full-blown Pathology
AbstractOligomers of the amyloid- β (Aβ) protein are suspected to be responsible for the development and progression of Alzheimer’s disease. Thus, the development of compounds that are able to eliminate already formed toxic Aβ oligomers is very desirable. Here, we describe the in vivo efficacy of the compound RD2, which was dev eloped to directly and specifically eliminate toxic Aβ oligomers. In a truly therapeutic, rather than a preventive study, oral treatment with RD2 was able to reverse cognitive deficits and significantly reduce Aβ pathology in old-aged transgenic Alzheimer’s Disea...
Source: Molecular Neurobiology - July 12, 2018 Category: Neurology Source Type: research

Impairment of Axonal Transport in Diabetes: Focus on the Putative Mechanisms Underlying Peripheral and Central Neuropathies
AbstractDiabetes mellitus is a chronic disease with numerous complications that severely impact on the quality of life of patients. Different neuropathies may arise as complications associated with the nervous system, both peripherally and at the central level. The mechanisms behind these neuronal complications are far from being clarified, but axonal transport impairment, a vital process for neuronal physiology, has been described in the context of experimental diabetes. Alterations in neuronal cytoskeleton and motor proteins, deficits in ATP supply or neuroinflammation, as processes that disturb the effective transport o...
Source: Molecular Neurobiology - July 12, 2018 Category: Neurology Source Type: research

Absence of Stress Response in Dorsal Raphe Nucleus in Modulator of Apoptosis 1-Deficient Mice
AbstractModulator of apoptosis 1 (MOAP-1) is a Bcl-2-associated X Protein (BAX)-associating protein that plays an important role in regulating apoptosis. It is highly enriched in the brain but its function in this organ remains unknown. Studies on BAX−/− mice suggested that disruption of programmed cell death may lead to abnormal emotional states. We thus hypothesize that MOAP-1−/− mice may also display stress-related behavioral differences and perhaps involved in stress responses in the brain and investigated if a depression-like trait exists in MOAP-1−/− mice, and if so, whether it is ...
Source: Molecular Neurobiology - July 12, 2018 Category: Neurology Source Type: research

Epigenetic Control of the Notch and Eph Signaling Pathways by the Prion Protein: Implications for Prion Diseases
AbstractAmong the ever-growing number of self-replicating proteins involved in neurodegenerative diseases, the prion protein PrP remains the most infamous for its central role in transmissible spongiform encephalopathies (TSEs). In these diseases, pathogenic prions propagate through a seeding mechanism, where normal PrPC molecules are converted into abnormally folded scrapie isoforms termed PrPSc. Since its discovery over 30  years ago, much advance has contributed to define the host-encoded cellular prion protein PrPC as a critical relay of prion-induced neuronal cell demise. A current consensual view is that the con...
Source: Molecular Neurobiology - July 11, 2018 Category: Neurology Source Type: research

Inhibition of the Nrf2/HO-1 Axis Suppresses the Mitochondria-Related Protection Promoted by Gastrodin in Human Neuroblastoma Cells Exposed to Paraquat
AbstractMitochondria are double-membrane organelles involved in the transduction of energy from different metabolic substrates into adenosine triphosphate (ATP) in mammalian cells. The oxidative phosphorylation system is comprised by the activity of the respiratory chain and the complex V (ATP synthase/ATPase). This system is dependent on oxygen gas (O2) in order to maintain a flux of electrons in the respiratory chain, since O2 is the final acceptor of these electrons. Electron leakage from this complex system leads to the continuous generation of reactive species in the cells. The mammalian cells exhibit certain mechanis...
Source: Molecular Neurobiology - July 11, 2018 Category: Neurology Source Type: research

Cortical Neurotoxic Astrocytes with Early ALS Pathology and miR-146a Deficit Replicate Gliosis Markers of Symptomatic SOD1G93A Mouse Model
AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron (MN) loss. Recent evidences highlight astrocytes as important players in MN death, but the mechanism-based neurotoxicity is still unknown. It is also unclear whether activation of astrocytes in ALS occurs differently in the cerebral cortex and spinal cord. We investigated glial and neuronal alterations in the cortex of SOD1G93A (mSOD1) mice in pre-symptomatic and symptomatic stages. We also characterized astrocytes isolated from the cortex of 7-day-old mSOD1 mice for their aberrancy and MN-induced degenerative eff...
Source: Molecular Neurobiology - July 11, 2018 Category: Neurology Source Type: research

Ischemic Injury-Induced CaMKII δ and CaMKIIγ Confer Neuroprotection Through the NF-κB Signaling Pathway
AbstractCa2+/calmodulin-dependent protein kinase II (CaMKII) has long been implicated in neuronal injury caused by acute ischemia/reperfusion (I/R). However, its precise role and regulatory mechanisms remain obscure. Here, we investigated the role of the CaMKII family in neuronal survival during I/R. Our data indicated thatCAMK2D/CaMKII δ andCAMK2G/CaMKII γ were selectively upregulated in a time-dependent manner at both transcriptional and protein levels after acute ischemia. Overexpression of CaMKIIδ promoted neuronal survival, while their depletion exacerbated ischemic neuronal death. Similar to CaMKII&...
Source: Molecular Neurobiology - July 11, 2018 Category: Neurology Source Type: research

Neuroglobin Expression in the Brain: a Story of Tissue Homeostasis Preservation
AbstractAfter its discovery in 2000, the notion grew that neuroglobin, a neuronal specific heme protein, is involved in cytoprotection. To date, neuroglobin levels have been positively correlated with a beneficial outcome in a plethora of neurotoxic insults, e.g., ischemic and traumatic brain injuries and Alzheimer ’s disease. The first part of this review goes further into these changes of neuroglobin expression upon different neuronal insults as well as the underlying regulation. In the second part, we shed light on the mechanisms by which neuroglobin contributes to neuroprotection, being (i) the scavengin g and de...
Source: Molecular Neurobiology - July 10, 2018 Category: Neurology Source Type: research

MTOR Pathway-Based Discovery of Genetic Susceptibility to L-DOPA-Induced Dyskinesia in Parkinson ’s Disease Patients
AbstractDyskinesia induced by L-DOPA administration (LID) is one of the most invalidating adverse effects of the gold standard treatment restoring dopamine transmission in Parkinson ’s disease (PD). However, LID manifestation in parkinsonian patients is variable and heterogeneous. Here, we performed a candidate genetic pathway analysis of the mTOR signaling cascade to elucidate a potential genetic contribution to LID susceptibility, since mTOR inhibition ameliorates LID in PD animal models. We screened 64 single nucleotide polymorphisms (SNPs) mapping to 57 genes of the mTOR pathway in a retrospective cohort of 401 P...
Source: Molecular Neurobiology - July 10, 2018 Category: Neurology Source Type: research

Anti-prion Protein Antibody 6D11 Restores Cellular Proteostasis of Prion Protein Through Disrupting Recycling Propagation of PrP Sc and Targeting PrP Sc for Lysosomal Degradation
AbstractPrPSc is an infectious and disease-specific conformer of the prion protein, which accumulation in the CNS underlies the pathology of prion diseases. PrPSc replicates by binding to the cellular conformer of the prion protein (PrPC) expressed by host cells and rendering its secondary structure a likeness of itself. PrPC is a plasma membrane anchored protein, which constitutively recirculates between the cell surface and the endocytic compartment. Since PrPSc engages PrPC along this trafficking pathway, its replication process is often referred to as “recycling propagation.” Certain monoclonal antibodies (...
Source: Molecular Neurobiology - July 9, 2018 Category: Neurology Source Type: research

Involvement of Claudin-11 in Disruption of Blood-Brain, -Spinal Cord, and -Arachnoid Barriers in Multiple Sclerosis
In conclusion, our present findings indicate that claudin-11 expression at the BBB, BSCB, and BAB, but not the BCSFB, is downregulated in multiple sclerosis, impairing the functional integrity of these barriers. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - July 8, 2018 Category: Neurology Source Type: research

Expression of the Cerebral Olfactory Receptors Olfr110/111 and Olfr544 Is Altered During Aging and in Alzheimer ’s Disease-Like Mice
AbstractA growing number of studies report the expression of olfactory receptors (ORs) in many non-chemosensory tissues and organs. However, within the brain, very few ectopic ORs are exhaustively documented. Their kinetic expression, cellular localization, and functions remain elusive. Using cDNA microarrays, quantitative PCR, and immunohistochemistry, we studied the cellular and sub-cellular localization of Olfr110/111 and Olfr544 and their timely expression in various brain areas of wild-type and transgenic Alzheimer ’s disease-like (5xFAD) mice. We observed that Olfr110/111 and Olfr544 proteins are mainly express...
Source: Molecular Neurobiology - July 8, 2018 Category: Neurology Source Type: research

Growth Factors and Neuroglobin in Astrocyte Protection Against Neurodegeneration and Oxidative Stress
AbstractNeurodegenerative diseases, such as Parkinson and Alzheimer, are among the main public health issues in the world due to their effects on life quality and high mortality rates. Although neuronal death is the main cause of disruption in the central nervous system (CNS) elicited by these pathologies, other cells such as astrocytes are also affected. There is no treatment for preventing the cellular death during neurodegenerative processes, and current drug therapy is focused on decreasing the associated motor symptoms. For these reasons, it has been necessary to seek new therapeutical procedures, including the use of...
Source: Molecular Neurobiology - July 7, 2018 Category: Neurology Source Type: research

Physical Exercise During Pregnancy Prevents Cognitive Impairment Induced by Amyloid- β in Adult Offspring Rats
AbstractAlzheimer ’s disease (AD) is the main aging-associated neurodegenerative disorder and is characterized by mitochondrial dysfunction, oxidative stress, synaptic failure, and cognitive decline. It has been a challenge to find disease course-modifying treatments. However, several studies demonstrated that regu lar physical activity and exercise are capable of promoting brain health by improving the cognitive function. Maternal lifestyle, including regular exercise during pregnancy, has also been shown to influence fetal development and disease susceptibility in adulthood through fetal metabolism programmi ng. He...
Source: Molecular Neurobiology - July 7, 2018 Category: Neurology Source Type: research

Endothelial Cell Dysfunction and Injury in Subarachnoid Hemorrhage
AbstractIn the brain, vascular endothelial cells conserve blood viscosity, control blood flow, and form the interface between central nervous system and circulating blood. Clinical outcome after aneurysmal subarachnoid hemorrhage is linked to early brain injury, cerebral vasospasm, and other causes of delayed cerebral ischemia. The cerebral vasculature remains a unique target for therapies since it becomes rapidly disrupted after subarachnoid hemorrhage, and damage to the blood vessels continues into the delayed injury phase. The current failure of therapies to improve clinical outcome warrants a re-evaluation of current t...
Source: Molecular Neurobiology - July 7, 2018 Category: Neurology Source Type: research

Pathological Modification of TDP-43 in Amyotrophic Lateral Sclerosis with SOD1 Mutations
AbstractAmyotrophic lateral sclerosis (ALS) is a fatal, adult-onset, progressive neurodegenerative disorder with no known cure. Cu/Zn-superoxide dismutase (SOD1) was the first identified protein associated with familial ALS (fALS). Recently, TAR DNA-binding protein 43 (TDP-43) has been found to be a principal component of ubiquitinated cytoplasmic inclusions in neurons and glia in ALS. However, it remains unclear whether these ALS-linked proteins partly have a shared pathogenesis. Here, we determine the association between mutant SOD1 and the modification of TDP-43 and the relationship of pathologic TDP-43 to neuronal cyto...
Source: Molecular Neurobiology - July 7, 2018 Category: Neurology Source Type: research

Myostatin Is Associated With Cognitive Decline in an Animal Model of Alzheimer ’s Disease
AbstractWith aging, there are progressive functional declines in multiple organ systems. One of the major physiological problems observed in aged people is skeletal muscle loss. This age-related muscle loss causes muscle weakness and disability, which in turn might reduce the quality of life in older adults and lead to the progression of several diseases, particularly Alzheimer ’s disease (AD). Some researchers have hypothesized that loss of muscle mass and strength is linked to the risk of developing AD. In addition, unintended weight loss often occurs in AD patients and might reflect dementia severity. However, the...
Source: Molecular Neurobiology - July 7, 2018 Category: Neurology Source Type: research

Small Molecule GSK-J1 Affects Differentiation of Specific Neuronal Subtypes in Developing Rat Retina
In this study, we focused on the role of potent histone demethylase inhibitor GSK-J1 as a blocker of Jumonji domain-containing protein 3 (Jmjd3) in early postnatal retinal development. Jmjd3 participates in different processes such as cell proliferation, apoptosis, differentiation, senescence, and cell reprogramming via demethylation of histone 3 lysine 27 trimethylation status (H3K27 me3). As a first approach, we determined the localization of Jmjd3 in neonate and adult rat retina. We observed that Jmjd3 accumulation is higher in the adult retina, which is consistent with the localization in the differentiated neurons, in...
Source: Molecular Neurobiology - July 7, 2018 Category: Neurology Source Type: research

Effects of Prion Protein on A β42 and Pyroglutamate-Modified AβpΕ3-42 Oligomerization and Toxicity
AbstractSoluble A β oligomers are widely recognized as the toxic forms responsible for triggering AD, and Aβ receptors are hypothesized to represent the first step in a neuronal cascade leading to dementia. Cellular prion protein (PrP) has been reported as a high-affinity binder of Aβ oligomers. The interactions o f PrP with both Aβ42 and the highly toxic N-truncated pyroglutamylated species (AβpE3-42) are here investigated, at a molecular level, by means of ThT fluorescence, NMR and TEM. We demonstrate that soluble PrP binds both Aβ42 and AβpE3-42, preferentially interacting with oligome...
Source: Molecular Neurobiology - July 6, 2018 Category: Neurology Source Type: research

Possible Involvement of PI3-K/Akt-Dependent GSK-3 β Signaling in Proliferation of Neural Progenitor Cells After Hypoxic Exposure
AbstractWe previously demonstrated that proliferation of endogenous neural progenitor cells is enhanced by cerebral ischemia and that phosphatidylinositol 3-kinase (PI3-K)/Akt-dependent glycogen synthase kinase (GSK)-3 β signaling is involved in ischemia-induced neurogenesis. It is important to learn more about the regulation of proliferation and differentiation of neural progenitor cells under ischemic conditions, as such knowledge that may serve as the basis for the development of new therapeutic approaches for stroke. However, it remains to be addressed whether a change in that signaling pathway is induced in neura...
Source: Molecular Neurobiology - July 6, 2018 Category: Neurology Source Type: research

Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement
AbstractPurinergic signaling is the main synaptic and non-synaptic signaling system in brain. ATP acts as a fast excitatory transmitter, while adenosine sets a global inhibitory tone within hippocampal neuronal networks. ATP and adenosine are interconnected by ectonucleotidase enzymes, which convert ATP to adenosine. Existing data point to the converging roles of ovarian steroids and purinergic signaling in synapse formation and refinement and synapse activity in the hippocampus. Therefore, in the present study, we have used enzyme histochemistry and expression analysis to obtain data on spatial distribution and expression...
Source: Molecular Neurobiology - July 6, 2018 Category: Neurology Source Type: research

Alcohol and Cocaine Exposure Modulates ABCB1 and ABCG2 Transporters in Male Alcohol-Preferring Rats
In this study, we determined the effects of voluntary ethanol consumption following repeated exposure to cocaine or vehicle on the relative mRNA and protein expression ofAbcg2/ABCG2 andAbcb1/ABCB1 in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) of male alcohol-preferring (P) rats. Male P rats were allowed free choice access to ethanol (15 and 30%v/v) and water for 5  weeks to establish baseline drinking behavior. The following week, rats were either injected with 20 mg/kg i.p. of cocaine or saline, once a day, for 7 days. The relative mRNA and protein expression ofAbcb1/ABCB1 andAbcg2/ABCG...
Source: Molecular Neurobiology - July 6, 2018 Category: Neurology Source Type: research

Viral Triggers and Inflammatory Mechanisms in Pediatric Epilepsy
AbstractExperimental and clinical findings suggest a crucial role for inflammation in the onset of pediatric seizures; this mechanism is not targeted by conventional antiepileptic drugs and may contribute to refractory epilepsy. Several triggers, including infection with neurotropic viruses such as human herpesvirus 6 (HHV-6), other herpesviruses, and picornaviruses, appear to induce activation of the innate and adaptive immune systems, which results in several neuroinflammatory responses, leading to enhanced neuronal excitability, and ultimately contributing to epileptogenesis. This review discusses the proposed mechanism...
Source: Molecular Neurobiology - July 5, 2018 Category: Neurology Source Type: research

Klotho at the Edge of Alzheimer ’s Disease and Senile Depression
AbstractKlotho, encoded by theKL gene, is a single-pass transmembrane protein and a circulating factor that plays a key role in cellular metabolism and body homeostasis and has been associated with age-related diseases. Alterations of this protein seem to influence the development of serotonergic neurons and could play a role in major depression in the elderly. Pretreatment of neurons with Klotho protein can avoid neuronal injury related to the toxic amyloid- β and glutamate, centrally related to the pathogenesis of Alzheimer’s disease (AD), in order that Klotho protein could play a neuroprotective role in AD pa...
Source: Molecular Neurobiology - July 5, 2018 Category: Neurology Source Type: research

Hyperglycemia-Driven Neuroinflammation Compromises BBB Leading to Memory Loss in Both Diabetes Mellitus (DM) Type 1 and Type 2 Mouse Models
AbstractEnd organ injury in diabetes mellitus (DM) is driven by microvascular compromise (including diabetic retinopathy and nephropathy). Cognitive impairment is a well-known complication of DM types 1 and 2; however, its mechanism(s) is(are) not known. We hypothesized that blood-brain barrier (BBB) compromise plays a key role in cognitive decline in DM. Using a DM type 1 model (streptozotocin injected C57BL/6 mice) and type 2 model (leptin knockout obese db/db mice), we showed enhanced BBB permeability and memory loss (Y maze, water maze) that are associated with hyperglycemia. Gene profiling in isolated microvessels fro...
Source: Molecular Neurobiology - July 5, 2018 Category: Neurology Source Type: research

Wnt-7a Stimulates Dendritic Spine Morphogenesis and PSD-95 Expression Through Canonical Signaling
AbstractWnt signaling regulates brain development and synapse maturation; however, the precise molecular mechanism remains elusive. Here, we report that Wnt-7a stimulates dendritic spine morphogenesis in the hippocampus via glycogen synthase kinase-3 β (GSK-3β) inhibition, triggering β-catenin/T cell factor/lymphoid enhancer factor (TCF/LEF)-dependent gene transcription and promoting postsynaptic density-95 (PSD-95) protein expression. In addition, wild-type mice treated with an inhibitor of β-catenin/TCF/LEF-mediated transcription showed a reduction in spatial memory acquisition accompanied by a reduct...
Source: Molecular Neurobiology - July 2, 2018 Category: Neurology Source Type: research

Soluble Amyloid Precursor Protein Alpha Interacts with alpha3-Na, K-ATPAse to Induce Axonal Outgrowth but Not Neuroprotection: Evidence for Distinct Mechanisms Underlying these Properties
AbstractAmyloid precursor protein (APP) is cleaved not only to generate the amyloid peptide (A ß), involved in neurodegenerative processes, but can also be metabolized by alpha secretase to produce and release soluble N-terminal APP (sAPPα), which has many properties including the induction of axonal elongation and neuroprotection. The mechanisms underlying the properties of sAPPα are not known. Here, we used proteomic analysis of mouse cortico-hippocampal membranes to identify the neuronal specific alpha3 (α3)-subunit of the plasma membrane enzyme Na, K-ATPase (NKA) as a new binding partner of sAPP...
Source: Molecular Neurobiology - June 9, 2018 Category: Neurology Source Type: research

Photobiomodulation Therapy Improves Acute Inflammatory Response in Mice: the Role of Cannabinoid Receptors/ATP-Sensitive K + Channel/p38-MAPK Signalling Pathway
AbstractAlthough photobiomodulation therapy (PBM) has been applied clinically for the treatment of pain and inflammation, wound healing, sports and soft tissue injuries, as well as to repair injured spinal cords and peripheral nerves, it remains unclear which molecular substrates (receptor) are implicated in the cellular mechanisms of PBM. Here, we reported that PBM (660  nm, 30 mW, 0.06 cm2, 50  J/cm2, plantar irradiation) significantly inhibited carrageenan-induced paw oedema, but not noxious thermal response, through positive modulation to both CB1 and CB2 cannabinoid receptors. The use of CB1 antago...
Source: Molecular Neurobiology - June 9, 2018 Category: Neurology Source Type: research

Paracrine and Intracrine Angiotensin 1-7/Mas Receptor Axis in the Substantia Nigra of Rodents, Monkeys, and Humans
AbstractIn addition to the classical hormonal (tissue-to-tissue) renin-angiotensin system (RAS), there are a paracrine (cell-to-cell) and an intracrine (intracellular/nuclear) RAS. A local paracrine brain RAS has been associated with several brain disorders, including Parkinson ’s disease (PD). Classically, angiotensin II (Ang II) is the main RAS effector peptide and acts through two major receptors: Ang II type 1 and 2 (AT1 and AT2) receptors. It has been shown that enhanced activation of the Ang II/AT1 axis exacerbates dopaminergic cell death. Several new components of the RAS have more recently been discovered. Ho...
Source: Molecular Neurobiology - June 9, 2018 Category: Neurology Source Type: research

Adaptor Protein APPL2 Affects Adult Antidepressant Behaviors and Hippocampal Neurogenesis via Regulating the Sensitivity of Glucocorticoid Receptor
In conclusion, APPL2 could be an important regulator for adult neurogenesis. APPL2 overexpression could blunt the activation of glucocorticoid receptor when undergoing environmental stress. Our study suggests that APPL2 might be a new therapeutic target for mental disorders. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - June 9, 2018 Category: Neurology Source Type: research

Validation of Reference Genes for Expression Studies in Human Meningiomas under Different Experimental Settings
AbstractQuantitative polymerase chain reaction (qPCR) is a sensitive technique for the quantitative analysis of gene expression levels. To compare mRNA transcripts across tumour and non-pathological tissue, appropriate reference genes are required for internal standardisation. Validation of these reference genes in meningiomas has not yet been reported. After mRNA transcription of meningioma (WHO grade I-III) and meningeal tissue from three different experimental sample types (fresh tissue, primary cell cultures and FFPE tissue), 13 candidate reference genes (ACTB,B2M,HPRT,VIM,GAPDH,YWHAZ,EIF4A2,MUC1,ATP5B,GNB2L,TUBB,CYC1,...
Source: Molecular Neurobiology - June 9, 2018 Category: Neurology Source Type: research

Natural Dietary Supplementation of Anthocyanins via PI3K/Akt/Nrf2/HO-1 Pathways Mitigate Oxidative Stress, Neurodegeneration, and Memory Impairment in a Mouse Model of Alzheimer ’s Disease
In conclusion, our data suggested that consumption and supplementation of natural-derived anti-oxidant neuroprotective ag ent such as anthocyanins may be beneficial and suggest new dietary-supplement strategies for intervention in and prevention of progressive neurodegenerative diseases, such as AD. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - June 9, 2018 Category: Neurology Source Type: research

The Role of WD40-Repeat Protein 62 (MCPH2) in Brain Growth: Diverse Molecular and Cellular Mechanisms Required for Cortical Development
AbstractGenetic disruptions of spindle/centrosome-associated WD40-repeat protein 62 (WDR62) are causative for autosomal recessive primary microcephaly (MCPH) and a broader range of cortical malformations. Since the identification of WDR62 as encoded by the MCPH2 locus in 2010, recent studies that have deleted/depleted WDR62 in various animal models of cortical development have highlighted conserved functions in brain growth. Here, we provide a timely review of our current understanding of WDR62 contributions in the self-renewal, expansion and fate specification of neural stem and progenitor cells that are critical for neoc...
Source: Molecular Neurobiology - June 9, 2018 Category: Neurology Source Type: research

Protein Biomarkers and Neuroproteomics Characterization of Microvesicles/Exosomes from Human Cerebrospinal Fluid Following Traumatic Brain Injury
This study sought to examine if CSF samples from severe TBI patients contain MV/E with unique protein contents. First, nanoparticle tracking analysis determined MV/E from TBI have a mode of 74 –98 nm in diameter, while control CSF MV/E have a mode of 99–104 nm. Also, there are more MV/E were isolated from TBI CSF (27.8–33.6 × 108/mL) than from control CSF (13.1 –18.5 × 108/mL). Transmission electron microscopy (TEM) visualization also confirmed characteristic MV/E morphology. Using targeted immunoblotting approach, we observed the presence of several...
Source: Molecular Neurobiology - June 9, 2018 Category: Neurology Source Type: research

Field Synopsis and Re-analysis of Systematic Meta-analyses of Genetic Association Studies in Multiple Sclerosis: a Bayesian Approach
AbstractTo provide an up-to-date summary of multiple sclerosis-susceptible gene variants and assess the noteworthiness in hopes of finding true associations, we investigated the results of 44 meta-analyses on gene variants and multiple sclerosis published through December 2016. Out of 70 statistically significant genotype associations, roughly a fifth (21%) of the comparisons showed noteworthy false-positive rate probability (FPRP) at a statistical power to detect an OR of 1.5 and at a prior probability of 10−6 assumed for a random single nucleotide polymorphism. These associations (IRF8/rs17445836,STAT3/rs744166,HLA...
Source: Molecular Neurobiology - June 9, 2018 Category: Neurology Source Type: research

Exposure to Hypertensive Disorders of Pregnancy Increases the Risk of Autism Spectrum Disorder in Affected Offspring
AbstractThere is growing awareness that prenatal adversity may increase the risk of autism spectrum disorder (ASD). Here, we examined the association between hypertensive disorders of pregnancy (HDP) and ASD risk at 7  years of age using the Millennium Cohort Study (MCS), a representative cohort of 13,192 children born in the UK from 2000 to 2001. We also sought to examine cytokine expression in the serum of women with pre-eclampsia, which is the most common HDP, and whether exposure of foetal neurons to this se rum could change patterns of neuronal growth. HDP were reported by mothers 9 months post-delivery. ASD...
Source: Molecular Neurobiology - June 9, 2018 Category: Neurology Source Type: research

Ketamine Self-Administration Elevates αCaMKII Autophosphorylation in Mood and Reward-Related Brain Regions in Rats
AbstractModulation of αCaMKII expression and phosphorylation is a feature shared by drugs of abuse with different mechanisms of action. Accordingly, we investigated whether αCaMKII expression and activation could be altered by self-administration of ketamine, a non-competitive antagonist of the NMDA glutamate receptor, with antidepressant and psychotomimetic as well as reinforcing properties. Rats self-administered ketamine at a sub-anesthetic dose for 43 days and were sacrificed 24 h after the last drug exposure; reward-related brain regions, such as medial prefrontal cortex (PFC), ventral striatum (...
Source: Molecular Neurobiology - June 9, 2018 Category: Neurology Source Type: research

The Effects of Extracellular Serum Concentration on APP Processing in Npc1-Deficient APP-Overexpressing N2a Cells
AbstractAmyloid precursor protein (APP) is cleaved by a set of proteases including α-/β-/γ- and recently identified η-secretases, generating C-terminal fragments (CTFs) of varying lengths and amyloid β (Aβ) peptides, which are considered to play a pivotal role in Alzheimer’s disease (AD) pathogenesis. Cellular cholesterol content/distribution can regulate the production/cl earance of APP metabolites and hence modify AD pathology. To determine the functional relation between endosomal-lysosomal (EL) cholesterol sequestration and APP metabolism, we used our recently developed mouse N2a-AN...
Source: Molecular Neurobiology - June 9, 2018 Category: Neurology Source Type: research

Multifaceted Regulation of ALDH1A1 by Cdk5 in Alzheimer ’s Disease Pathogenesis
This study revealed multifaceted regulation of ALDH1A1 by Cdk5 in Alzheimer ’s disease (AD) pathogenesis. ALDH1A1 is a multifunctional enzyme with dehydrogenase, esterase, and anti-oxidant activities. ALDH1A1 is also a major regulator of retinoic acid (RA) signaling, which is critical for normal brain homeostasis. We identified ALDH1A1 as both physiological and pathologic al target of Cdk5. First, under neurotoxic conditions, Cdk5-induced oxidative stress upregulatesALDH1A1 transcription. Second, Cdk5 increases ALDH1A1 levels by preventing its ubiquitylation via direct phosphorylation. Third, ALDH1A1 phosphorylation ...
Source: Molecular Neurobiology - June 8, 2018 Category: Neurology Source Type: research