Repairing the Brain by SCF+G-CSF Treatment at 6 Months Postexperimental Stroke: Mechanistic Determination of the Causal Link Between Neurovascular Regeneration and Motor Functional Recovery
This study provides novel insights into the development of new restorative strategies for stroke recovery. (Source: ASN Neuro)
Source: ASN Neuro - August 8, 2016 Category: Neuroscience Authors: Cui, L., Wang, D., McGillis, S., Kyle, M., Zhao, L.-R. Tags: Original Article Source Type: research
Antioxidant Protection of NADPH-Depleted Oligodendrocyte Precursor Cells Is Dependent on Supply of Reduced Glutathione
The pentose phosphate pathway is the main source of NADPH, which by reducing oxidized glutathione, contributes to antioxidant defenses. Although oxidative stress plays a major role in white matter injury, significance of NADPH for oligodendrocyte survival has not been yet investigated. It is reported here that the NADPH antimetabolite 6-amino-NADP (6AN) was cytotoxic to cultured adult rat spinal cord oligodendrocyte precursor cells (OPCs) as well as OPC-derived oligodendrocytes. The 6AN-induced necrosis was preceded by increased production of superoxide, NADPH depletion, and lower supply of reduced glutathione. Moreover, s...
Source: ASN Neuro - July 20, 2016 Category: Neuroscience Authors: Kilanczyk, E., Saraswat Ohri, S., Whittemore, S. R., Hetman, M. Tags: Original Article Source Type: research
A Complex Interaction Between Reduced Reelin Expression and Prenatal Organophosphate Exposure Alters Neuronal Cell Morphology
Genetic and environmental factors are both likely to contribute to neurodevelopmental disorders including schizophrenia, autism spectrum disorders, and major depressive disorders. Prior studies from our laboratory and others have demonstrated that the combinatorial effect of two factors—reduced expression of reelin protein and prenatal exposure to the organophosphate pesticide chlorpyrifos oxon—gives rise to acute biochemical effects and to morphological and behavioral phenotypes in adolescent and young adult mice. In the current study, we examine the consequences of these factors on reelin protein expression a...
Source: ASN Neuro - June 29, 2016 Category: Neuroscience Authors: Mullen, B. R., Ross, B., Chou, J. W., Khankan, R., Khialeeva, E., Bui, K., Carpenter, E. M. Tags: Original Article Source Type: research
Zinc in Multiple Sclerosis: A Systematic Review and Meta-Analysis
In the last 35 years, zinc (Zn) has been examined for its potential role in the disease multiple sclerosis (MS). This review gives an overview of the possible role of Zn in the pathogenesis of MS as well as a meta-analysis of studies having measured Zn in serum or plasma in patients with MS. Searching the databases PubMed and EMBASE as well as going through reference lists in included articles 24 studies were found measuring Zn in patients with MS. Of these, 13 met inclusion criteria and were included in the meta-analysis. The result of the meta-analysis shows a reduction in serum or plasma Zn levels in patients with MS wi...
Source: ASN Neuro - June 8, 2016 Category: Neuroscience Authors: Bredholt, M., Frederiksen, J. L. Tags: Review Source Type: research
Perk Ablation Ameliorates Myelination in S63del-Charcot-Marie-Tooth 1B Neuropathy
In peripheral nerves, P0 glycoprotein accounts for more than 20% of myelin protein content. P0 is synthesized by Schwann cells, processed in the endoplasmic reticulum (ER) and enters the secretory pathway. However, the mutant P0 with S63 deleted (P0S63del) accumulates in the ER lumen and induces a demyelinating neuropathy in Charcot–Marie–Tooth disease type 1B (CMT1B)–S63del mice. Accumulation of P0S63del in the ER triggers a persistent unfolded protein response. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) is an ER stress sensor that phosphorylates eukaryotic initiation factor 2 alpha (eIF...
Source: ASN Neuro - April 18, 2016 Category: Neuroscience Authors: Musner, N., Sidoli, M., Zambroni, D., Del Carro, U., Ungaro, D., DAntonio, M., Feltri, M. L., Wrabetz, L. Tags: Original Article Source Type: research
Hydroxysafflor Yellow A Protects Neurons From Excitotoxic Death through Inhibition of NMDARs
Excessive glutamate release causes overactivation of N-methyl d-aspartate receptors (NMDARs), leading to excitatory neuronal damage in cerebral ischemia. Hydroxysafflor yellow A (HSYA), a compound extracted from Carthamus tinctorius L., has been reported to exert a neuroprotective effect in many pathological conditions, including brain ischemia. However, the underlying mechanism of HSYA's effect on neurons remains elusive. In the present study, we conducted experiments using patch-clamp recording of mouse hippocampal slices. In addition, we performed Ca2+ imaging, Western blots, as well as mitochondrial-targeted circularly...
Source: ASN Neuro - April 9, 2016 Category: Neuroscience Authors: Wang, X., Ma, Z., Fu, Z., Gao, S., Yang, L., Jin, Y., Sun, H., Wang, C., Fan, W., Chen, L., Zheng, Q.-Y., Bi, G., Ma, C.-L. Tags: Original Article Source Type: research
Large-Scale Functional RNAi Screen in C. elegans Identifies TGF-{beta} and Notch Signaling Pathways as Modifiers of CACNA1A
Variants in CACNA1A that encodes the pore-forming α1-subunit of human voltage-gated Cav2.1 (P/Q-type) Ca2+ channels cause several autosomal-dominant neurologic disorders, including familial hemiplegic migraine type 1, episodic ataxia type 2, and spinocerebellar ataxia type 6. To identify modifiers of incoordination in movement disorders, we performed a large-scale functional RNAi screen, using the Caenorhabditis elegans strain CB55, which carries a truncating mutation in the unc-2 gene, the worm ortholog for the human CACNA1A. The screen was carried out by the feeding method in 96-well liquid culture format, using th...
Source: ASN Neuro - March 21, 2016 Category: Neuroscience Authors: Pereira, M. d. C., Morais, S., Sequeiros, J., Alonso, I. Tags: Original Article Source Type: research
Refined Analysis of Brain Energy Metabolism Using In Vivo Dynamic Enrichment of 13C Multiplets
Carbon-13 nuclear magnetic resonance spectroscopy in combination with the infusion of 13C-labeled precursors is a unique approach to study in vivo brain energy metabolism. Incorporating the maximum information available from in vivo localized 13C spectra is of importance to get broader knowledge on cerebral metabolic pathways. Metabolic rates can be quantitatively determined from the rate of 13C incorporation into amino acid neurotransmitters such as glutamate and glutamine using suitable mathematical models. The time course of multiplets arising from 13C-13C coupling between adjacent carbon atoms was expected to...
Source: ASN Neuro - March 11, 2016 Category: Neuroscience Authors: Dehghani M., M., Lanz, B., Duarte, J. M. N., Kunz, N., Gruetter, R. Tags: Original Article Source Type: research
Astrocytic Ephrin-B1 Regulates Synapse Remodeling Following Traumatic Brain Injury
Traumatic brain injury (TBI) can result in tissue alterations distant from the site of the initial injury, which can trigger pathological changes within hippocampal circuits and are thought to contribute to long-term cognitive and neuropsychological impairments. However, our understanding of secondary injury mechanisms is limited. Astrocytes play an important role in brain repair after injury and astrocyte-mediated mechanisms that are implicated in synapse development are likely important in injury-induced synapse remodeling. Our studies suggest a new role of ephrin-B1, which is known to regulate synapse development in neu...
Source: ASN Neuro - February 29, 2016 Category: Neuroscience Authors: Nikolakopoulou, A. M., Koeppen, J., Garcia, M., Leish, J., Obenaus, A., Ethell, I. M. Tags: Original Article Source Type: research
Ganglioside-Dependent Neural Stem Cell Proliferation in Alzheimers Disease Model Mice
The aggregation and formation of amyloid plaques by amyloid β-peptides (Aβs) is believed to be one of the pathological hallmarks of Alzheimer’s disease (AD). Intriguingly, Aβs have also been shown to possess proliferative effects on neural stem cells (NSCs). Many essential cellular processes in NSCs, such as fate determination and proliferation, are heavily influenced by cell surface glycoconjugates, including gangliosides. It has recently been shown that Aβ1-42 alters several key glycosyltransferases and glycosidases. To further define the effects of Aβs and to clarify the potential mechanis...
Source: ASN Neuro - December 23, 2015 Category: Neuroscience Authors: Koon, N. A., Itokazu, Y., Yu, R. K. Tags: Original Article Source Type: research
Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury
We investigated the effects of the administration of docosahexaenoic acid (DHA) post-traumatic brain injury (TBI) on reducing neuroinflammation. TBI was induced by cortical contusion injury in Sprague Dawley rats. Either DHA (16 mg/kg in dimethyl sulfoxide) or vehicle dimethyl sulfoxide (1 ml/kg) was administered intraperitonially at 5 min after TBI, followed by a daily dose for 3 to 21 days. TBI triggered activation of microglia or macrophages, detected by an increase of Iba1 positively stained microglia or macrophages in peri-lesion cortical tissues at 3, 7, and 21 days post-TBI. The inflammatory response was further cha...
Source: ASN Neuro - December 18, 2015 Category: Neuroscience Authors: Harvey, L. D., Yin, Y., Attarwala, I. Y., Begum, G., Deng, J., Yan, H. Q., Dixon, C. E., Sun, D. Tags: Original Article Source Type: research
A Cytotoxic, Co-operative Interaction Between Energy Deprivation and Glutamate Release From System xc- Mediates Aglycemic Neuronal Cell Death
The astrocyte cystine/glutamate antiporter (system xc–) contributes substantially to the excitotoxic neuronal cell death facilitated by glucose deprivation. The purpose of this study was to determine the mechanism by which this occurred. Using pure astrocyte cultures, as well as, mixed cortical cell cultures containing both neurons and astrocytes, we found that neither an enhancement in system xc– expression nor activity underlies the excitotoxic effects of aglycemia. In addition, using three separate bioassays, we demonstrate no change in the ability of glucose-deprived astrocytes—either cultured alone o...
Source: ASN Neuro - November 9, 2015 Category: Neuroscience Authors: Thorn, T. L., He, Y., Jackman, N. A., Lobner, D., Hewett, J. A., Hewett, S. J. Tags: Original Article Source Type: research
The Circadian Clock Gene Period1 Connects the Molecular Clock to Neural Activity in the Suprachiasmatic Nucleus
In this study, we sought to examine how the clock gene Period1 (Per1) regulates the electrical activity in the mouse SCN by transiently and selectively decreasing levels of PER1 through use of an antisense oligodeoxynucleotide. We found that this treatment effectively reduced SCN neural activity. Direct current injection to restore the normal membrane potential partially, but not completely, returned firing rate to normal levels. The antisense treatment also reduced baseline [Ca2+]i levels as measured by Fura2 imaging technique. Whole cell patch clamp recording techniques were used to examine which specific potassium curre...
Source: ASN Neuro - November 9, 2015 Category: Neuroscience Authors: Kudo, T., Block, G. D., Colwell, C. S. Tags: Original Article Source Type: research
Ultrastructural Correlates of Enhanced Norepinephrine and Neuropeptide Y Cotransmission in the Spontaneously Hypertensive Rat Brain
The spontaneously hypertensive rat (SHR) replicates many clinically relevant features of human essential hypertension and also exhibits behavioral symptoms of attention-deficit/hyperactivity disorder and dementia. The SHR phenotype is highly complex and cannot be explained by a single genetic or physiological mechanism. Nevertheless, numerous studies including our own work have revealed striking differences in central catecholaminergic transmission in SHR such as increased vesicular catecholamine content in the ventral brainstem. Here, we used immunolabeling followed by confocal microscopy and electron microscopy to quanti...
Source: ASN Neuro - October 29, 2015 Category: Neuroscience Authors: Kourtesis, I., Kasparov, S., Verkade, P., Teschemacher, A. G. Tags: Original Article Source Type: research
Disruption of Fractalkine Signaling Leads to Microglial Activation and Neuronal Damage in the Diabetic Retina
Fractalkine (CX3CL1 or FKN) is a membrane-bound chemokine expressed on neuronal membranes and is proteolytically cleaved to shed a soluble chemoattractant domain. FKN signals via its unique receptor CX3CR1 expressed on microglia and other peripheral leukocytes. The aim of this study is to determine the role of CX3CR1 in inflammatory-mediated damage to retinal neurons using a model of diabetic retinopathy. For this, we compared neuronal, microglial, and astroglial densities and inflammatory response in nondiabetic and diabetic (Ins2Akita) CX3CR1-wild-type and CX3CR1-deficient mice at 10 and 20 weeks of age. Our results show...
Source: ASN Neuro - October 29, 2015 Category: Neuroscience Authors: Cardona, S. M., Mendiola, A. S., Yang, Y.-C., Adkins, S. L., Torres, V., Cardona, A. E. Tags: Original Article Source Type: research
