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ASN Neuro

Sahar Farajnia, Johanna H Meijer, Stephan Michel
One feature of the mammalian circadian clock, situated in the suprachiasmatic nucleus (SCN), is its ability to measure day length and thereby contribute to the seasonal adaptation of physiology and behavior. The timing signal from the SCN, namely the 24 hr pattern of electrical activity, is adjusted according to the photoperiod being broader in long days and narrower in short days. Vasoactive intestinal peptide and gamma-aminobutyric acid play a crucial role in intercellular communication within the SCN and contribute to the seasonal changes in phase distribution...
October 2016: ASN Neuro
Scott A Sands, Regis Leung-Toung, Yingsheng Wang, John Connelly, Steven M LeVine
Histochemical methods of detecting iron in the rodent brain result mainly in the labeling of oligodendrocytes, but as all cells utilize iron, this observation suggests that much of the iron in the central nervous system goes undetected. Paraffin embedding of tissue is a standard procedure that is used to prepare sections for microscopic analysis. In the present study, we questioned whether we could modify the iron histochemical procedure to enable a greater detection of iron in paraffin sections. Indeed, various modifications led to the widespread labeling of iron in mouse brain tissue (for instance, labeling of neurons and neuropil)...
October 2016: ASN Neuro
Joshua D Aaker, Benayahu Elbaz, Yuwen Wu, Timothy J Looney, Li Zhang, Bruce T Lahn, Brian Popko
The transcriptional program that controls oligodendrocyte maturation and central nervous system (CNS) myelination has not been fully characterized. In this study, we use high-throughput RNA sequencing to analyze how the loss of a key transcription factor, zinc finger protein 191 (ZFP191), results in oligodendrocyte development abnormalities and CNS hypomyelination. Using a previously described mutant mouse that is deficient in ZFP191 protein expression (Zfp191(null)), we demonstrate that key transcripts are reduced in the whole brain as well as within oligodendrocyte lineage cells cultured in vitro To determine whether the loss of myelin seen in Zfp191(null) mice contributes indirectly to these perturbations, we also examined the transcriptome of a well-characterized mouse model of hypomyelination, in which the myelin structural protein myelin basic protein (MBP) is deficient...
October 2016: ASN Neuro
Brandon J Dixon, Di Chen, Yang Zhang, Jerry Flores, Jay Malaguit, Derek Nowrangi, John H Zhang, Jiping Tang
Neonatal hypoxic-ischemic encephalopathy (HIE) is an injury that often leads to detrimental neurological deficits. Currently, there are no established therapies for HIE and it is critical to develop treatments that provide protection after HIE. The objective of this study was to investigate the ability of interferon beta (IFNβ) to provide neuroprotection and reduce apoptosis after HIE. Postnatal Day 10 rat pups were subjected to unilateral carotid artery ligation followed by 2.5 hr of exposure to hypoxia (8% O2)...
October 2016: ASN Neuro
Dongpei Li, Seigo Usuki, Brandy Quarles, Michael H Rivner, Toshio Ariga, Robert K Yu
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. Although the etiology of ALS is obscure, genetic studies of familiar ALS suggest a multifactorial etiology for this condition. Similarly, there probably are multiple causes for sporadic ALS. Autoimmune-mediated motor neuron dysfunction is one proposed etiology for sporadic ALS. In the present study, anti-glycolipid antibodies including GM1, GD1b, GD3, and sulfoglucuronosyl paragloboside (SGPG) were investigated in the sera of a large number of patient samples, including 113 ALS patients and 50 healthy controls, by means of enzyme-linked immunosorbent assay with affinity parametric complex criterion evaluation and thin-layer chromatography immunooverlay (immuno-TLC)...
October 2016: ASN Neuro
Donají Chi-Castañeda, Arturo Ortega
Circadian rhythms are periodic patterns in biological processes that allow the organisms to anticipate changes in the environment. These rhythms are driven by the suprachiasmatic nucleus (SCN), the master circadian clock in vertebrates. At a molecular level, circadian rhythms are regulated by the so-called clock genes, which oscillate in a periodic manner. The protein products of clock genes are transcription factors that control their own and other genes' transcription, collectively known as "clock-controlled genes...
October 2016: ASN Neuro
Natalie A Wheeler, Babette Fuss, Pamela E Knapp, ShiPing Zou
White matter injury has been frequently reported in HIV(+) patients. Previous studies showed that HIV-1 Tat (transactivator of transcription), a viral protein that is produced and secreted by HIV-infected cells, is toxic to young, immature oligodendrocytes (OLGs). Adding Tat to the culture medium reduced the viability of immature OLGs, and the surviving OLGs exhibited reduced process networks. OLGs produce and secrete autotaxin (ATX), an ecto-enzyme containing a lysophospholipase D (lysoPLD) activity that converts lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a lipid signaling molecule that stimulates OLG differentiation...
October 2016: ASN Neuro
Reiji Yamazaki, Tomoko Ishibashi, Hiroko Baba, Yoshihide Yamaguchi
Myelin is a special multilamellar structure involved in various functions in the nervous system. In the central nervous system, the oligodendrocyte (OL) produces myelin and has a unique morphology. OLs have a dynamic membrane sorting system associated with cytoskeletal organization, which aids in the production of myelin. Recently, it was reported that the assembly and disassembly of actin filaments is crucial for myelination. However, the partner myosin molecule which associates with actin filaments during the myelination process has not yet been identified...
October 2016: ASN Neuro
Salman Goudarzi, Andrea Rivera, Arthur M Butt, Sassan Hafizi
A key aim of therapy for multiple sclerosis (MS) is to promote the regeneration of oligodendrocytes and remyelination in the central nervous system (CNS). The present study provides evidence that the vitamin K-dependent protein growth arrest specific 6 (Gas6) promotes such repair in in vitro cultures of mouse optic nerve and cerebellum. We first determined expression of Gas6 and TAM (Tyro3, Axl, Mer) receptors in the mouse CNS, with all three TAM receptors increasing in expression through postnatal development, reaching maximal levels in the adult...
October 2016: ASN Neuro
Neha Sharma, Nicholas W Colangelo, Sonia M de Toledo, Edouard I Azzam
Harmful effects that alter the homeostasis of neural stem or progenitor cells (NSPs) can affect regenerative processes in the central nervous system. We investigated the effect of soluble factors secreted by control or (137)Cs-γ-irradiated glioblastoma or medulloblastoma cells on redox-modulated endpoints in recipient human NSPs. Growth medium harvested from the nonirradiated brain tumor cells, following 24 h of growth, induced prominent oxidative stress in recipient NSPs as judged by overall increases in mitochondrial superoxide radical levels (p < ...
August 2016: ASN Neuro
Melissa Smallwood, Ashley Sareen, Emma Baker, Rachel Hannusch, Eddy Kwessi, Tyisha Williams
Autism spectrum disorder (ASD) is a perplexing and pervasive developmental disorder characterized by social difficulties, communicative deficits, and repetitive behavior. The increased rate of ASD diagnosis has raised questions concerning the genetic and environmental factors contributing to the development of this disorder; meanwhile, the cause of ASD remains unknown. This study surveyed mothers of ASD and non-ASD children to determine possible effects of labor and delivery (L&D) drugs on the development of ASD...
August 2016: ASN Neuro
Ewa Kilanczyk, Sujata Saraswat Ohri, Scott R Whittemore, Michal Hetman
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...
August 2016: ASN Neuro
Lili Cui, Dandan Wang, Sandra McGillis, Michele Kyle, Li-Ru Zhao
Stroke, a leading cause of adult disability in the world, is a severe medical condition with limited treatment. Physical therapy, the only treatment available for stroke rehabilitation, appears to be effective within 6 months post-stroke. Here, we have mechanistically determined the efficacy of combined two hematopoietic growth factors, stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF; SCF + G-CSF), in brain repair 6 months after cortical infarct induction in the transgenic mice carrying yellow fluorescent protein in Layer V pyramidal neurons (Thy1-YFP-H)...
June 2016: ASN Neuro
Brian R Mullen, Brennan Ross, Joan Wang Chou, Rana Khankan, Elvira Khialeeva, Kimberly Bui, Ellen M Carpenter
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...
June 2016: ASN Neuro
Mikkel Bredholt, Jette Lautrup Frederiksen
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...
June 2016: ASN Neuro
Nicolò Musner, Mariapaola Sidoli, Desireè Zambroni, Ubaldo Del Carro, Daniela Ungaro, Maurizio D'Antonio, Maria L Feltri, Lawrence Wrabetz
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 (eIF2alpha) in order to attenuate protein synthesis...
March 2016: ASN Neuro
Xingtao Wang, Zhiyuan Ma, Zhongxiao Fu, Su Gao, Liu Yang, Yan Jin, Hui Sun, Chaoyun Wang, Weiming Fan, Lin Chen, Qing-Yin Zheng, Guoqiang Bi, Chun-Lei Ma
Excessive glutamate release causes overactivation of N-methyld-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...
March 2016: ASN Neuro
Maria da Conceição Pereira, Sara Morais, Jorge Sequeiros, Isabel Alonso
Variants in CACNA1A that encodes the pore-forming α1-subunit of human voltage-gated Cav2.1 (P/Q-type) Ca(2+)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 elegansstrain CB55, which carries a truncating mutation in the unc-2gene, the worm ortholog for the human CACNA1A The screen was carried out by the feeding method in 96-well liquid culture format, using the ORFeome v1...
March 2016: ASN Neuro
Masoumeh Dehghani M, Bernard Lanz, João M N Duarte, Nicolas Kunz, Rolf Gruetter
Carbon-13 nuclear magnetic resonance spectroscopy in combination with the infusion of (13)C-labeled precursors is a unique approach to study in vivo brain energy metabolism. Incorporating the maximum information available from in vivo localized (13)C spectra is of importance to get broader knowledge on cerebral metabolic pathways. Metabolic rates can be quantitatively determined from the rate of (13)C incorporation into amino acid neurotransmitters such as glutamate and glutamine using suitable mathematical models...
March 2016: ASN Neuro
Angeliki M Nikolakopoulou, Jordan Koeppen, Michael Garcia, Joshua Leish, Andre Obenaus, Iryna M Ethell
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...
January 2016: ASN Neuro
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