A Distinct Class of Antibodies May Be an Indicator of Gray Matter Autoimmunity in Early and Established Relapsing Remitting Multiple Sclerosis Patients
We have previously identified a distinct class of antibodies expressed by B cells in the cerebrospinal fluid (CSF) of early and established relapsing remitting multiple sclerosis (RRMS) patients that is not observed in healthy donors. These antibodies contain a unique pattern of mutations in six codons along VH4 antibody genes that we termed the antibody gene signature (AGS). In fact, patients who have such B cells in their CSF are identified as either having RRMS or developing RRMS in the future. As mutations in antibody genes increase antibody affinity for particular antigens, the goal for this study was to investigate w...
Source: ASN Neuro - October 21, 2015 Category: Neuroscience Authors: Ligocki, A. J., Rivas, J. R., Rounds, W. H., Guzman, A. A., Li, M., Spadaro, M., Lahey, L., Chen, D., Henson, P. M., Graves, D., Greenberg, B. M., Frohman, E. M., Sally Ward, E., Robinson, W., Meinl, E., White, C. L., Stowe, A. M., Monson, N. L. Tags: Original Article Source Type: research
Expression of the Astrocyte Water Channel Aquaporin-4 in the Mouse Brain
In this study, we used Western blotting and immunohistochemical techniques to characterize AQP4 expression and localization throughout the mouse brain. We observed AQP4 expression throughout the forebrain, subcortical areas, and brainstem. AQP4 protein levels were highest in the cerebellum with lower expression in the cortex and hippocampus. We found that AQP4 immunoreactivity was profuse on glial cells bordering ventricles, blood vessels, and subarachnoid space. Throughout the brain, AQP4 was expressed on astrocytic end-feet surrounding blood vessels but was also heterogeneously expressed in brain tissue parenchyma and ne...
Source: ASN Neuro - October 21, 2015 Category: Neuroscience Authors: Hubbard, J. A., Hsu, M. S., Seldin, M. M., Binder, D. K. Tags: Original Article Source Type: research
Osmotic Edema Rapidly Increases Neuronal Excitability Through Activation of NMDA Receptor-Dependent Slow Inward Currents in Juvenile and Adult Hippocampus
Cellular edema (cell swelling) is a principal component of numerous brain disorders including ischemia, cortical spreading depression, hyponatremia, and epilepsy. Cellular edema increases seizure-like activity in vitro and in vivo, largely through nonsynaptic mechanisms attributable to reduction of the extracellular space. However, the types of excitability changes occurring in individual neurons during the acute phase of cell volume increase remain unclear. Using whole-cell patch clamp techniques, we report that one of the first effects of osmotic edema on excitability of CA1 pyramidal cells is the generation of...
Source: ASN Neuro - October 21, 2015 Category: Neuroscience Authors: Lauderdale, K., Murphy, T., Tung, T., Davila, D., Binder, D. K., Fiacco, T. A. Tags: Original Article Source Type: research
Crosstalk Between MAPK/ERK and PI3K/AKT Signal Pathways During Brain Ischemia/Reperfusion
The epidermal growth factor receptor (EGFR) is linked to the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Raf/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK1/2) signaling pathways. During brain ischemia/reperfusion, EGFR could be transactivated, which stimulates these intracellular signaling cascades that either protect cells or potentiate cell injury. In the present study, we investigated the activation of EGFR, PI3K/AKT, and Raf/MAPK/ERK1/2 during ischemia or reperfusion of the brain using the middle cerebral artery occlusion model. We found that EGFR was phosphoryla...
Source: ASN Neuro - October 6, 2015 Category: Neuroscience Authors: Zhou, J., Du, T., Li, B., Rong, Y., Verkhratsky, A., Peng, L. Tags: Original Article Source Type: research
Glial Fibrillary Acidic Protein-Expressing Glia in the Mouse Lung
We describe the morphology of non-myelinating Schwann cells in the lung and verify that they express glial fibrillary acidic protein and S100, a classic glial marker. Furthermore, we characterize the relationship of non-myelinating Schwann cells to pulmonary nerves. Finally, we report tools for studying their function, including a commercially available transgenic mouse line. (Source: ASN Neuro)
Source: ASN Neuro - October 6, 2015 Category: Neuroscience Authors: Suarez-Mier, G. B., Buckwalter, M. S. Tags: Original Article Source Type: research
Intranasal Delivery of Apelin-13 Is Neuroprotective and Promotes Angiogenesis After Ischemic Stroke in Mice
This study demonstrates a noninvasive intranasal delivery of apelin-13 after stroke, suggesting that the reduced inflammatory activities, decreased cell death, and increased angiogenesis contribute to the therapeutic benefits of apelin-13. (Source: ASN Neuro)
Source: ASN Neuro - September 21, 2015 Category: Neuroscience Authors: Chen, D., Lee, J., Gu, X., Wei, L., Yu, S. P. Tags: Original Article Source Type: research
Axo-Glia Interaction Preceding CNS Myelination Is Regulated by Bidirectional Eph-Ephrin Signaling
In the central nervous system, myelination of axons is required to ensure fast saltatory conduction and for survival of neurons. However, not all axons are myelinated, and the molecular mechanisms involved in guiding the oligodendrocyte processes toward the axons to be myelinated are not well understood. Only a few negative or positive guidance clues that are involved in regulating axo-glia interaction prior to myelination have been identified. One example is laminin, known to be required for early axo-glia interaction, which functions through α6β1 integrin. Here, we identify the Eph-ephrin family of guidance re...
Source: ASN Neuro - September 8, 2015 Category: Neuroscience Authors: Linneberg, C., Harboe, M., Laursen, L. S. Tags: Original Article Source Type: research
Activation of Neuropeptide Y Receptors Modulates Retinal Ganglion Cell Physiology and Exerts Neuroprotective Actions In Vitro
In conclusion, we found modulatory effects of NPY application that for the first time were detected at the level of RGCs. However, further studies are needed to evaluate whether NPY neuroprotective actions detected in retinal explants can be translated into animal models of retinal degenerative diseases. (Source: ASN Neuro)
Source: ASN Neuro - August 26, 2015 Category: Neuroscience Authors: Martins, J., Elvas, F., Brudzewsky, D., Martins, T., Kolomiets, B., Tralhao, P., Gotzsche, C. R., Cavadas, C., Castelo-Branco, M., Woldbye, D. P. D., Picaud, S., Santiago, A. R., Ambrosio, A. F. Tags: Original Article Source Type: research
SORT1 Mutation Resulting in Sortilin Deficiency and p75NTR Upregulation in a Family With Essential Tremor
In this study, whole exome sequencing and subsequent approaches were performed in a family with an autosomal dominant form of early-onset ET. Functional analyses including mutagenesis, cell culture, gene expression, enzyme-linked immunosorbent, and apoptosis assays were also performed. A disease-segregating mutation (p.Gly171Ala), absent in normal population, was identified in the SORT1 gene. The p.Gly171Ala mutation was shown not only to impair the expression of its encoding protein sortilin but also the mRNA levels of its binding partner p75 neurotrophin receptor that is known to be implicated in brain injury, neuronal a...
Source: ASN Neuro - August 21, 2015 Category: Neuroscience Authors: Sanchez, E., Bergareche, A., Krebs, C. E., Gorostidi, A., Makarov, V., Ruiz-Martinez, J., Chorny, A., Lopez de Munain, A., Marti-Masso, J. F., Paisan-Ruiz, C. Tags: Original Article Source Type: research
Nrf2 and HSF-1 Pathway Activation via Hydroquinone-Based Proelectrophilic Small Molecules Is Regulated by Electrochemical Oxidation Potential
Activation of the Kelch-like ECH-associated protein 1/nuclear factor (erythroid-derived 2)-like 2 and heat-shock protein 90/heat-shock factor-1 signal-transduction pathways plays a central role in combatting cellular oxidative damage and related endoplasmic reticulum stress. Electrophilic compounds have been shown to be activators of these transcription-mediated responses through S-alkylation of specific regulatory proteins. Previously, we reported that a prototype compound (D1, a small molecule representing a proelectrophilic, para-hydroquinone species) exhibited neuroprotective action by activating both of these pathways...
Source: ASN Neuro - August 3, 2015 Category: Neuroscience Authors: Satoh, T., Stalder, R., McKercher, S. R., Williamson, R. E., Roth, G. P., Lipton, S. A. Tags: Original Article Source Type: research
The Role of Negative Charge in the Delivery of Quantum Dots to Neurons
In this study, we compared three zwitterionic QD coatings differing only in their regions of positive or negative charge, as well as a positively charged (NH2) polyethylene glycol (PEG) coat, for their ability to deliver the cell-membrane-penetrating chaperone lipopeptide JB577 (WG(Palmitoyl)VKIKKP9G2H6) to individual cells in neonatal rat hippocampal slices. We confirm both that preferential uptake in neurons, and the lack of uptake in glia, is strongly associated with having a region of greater negative charge on the QD coating. In addition, the role of negatively charged chondroitin sulfate of the extracellular matrix (...
Source: ASN Neuro - August 3, 2015 Category: Neuroscience Authors: Walters, R., Medintz, I. L., Delehanty, J. B., Stewart, M. H., Susumu, K., Huston, A. L., Dawson, P. E., Dawson, G. Tags: Original Article Source Type: research
Forced Exercise Preconditioning Attenuates Experimental Autoimmune Neuritis by Altering Th1 Lymphocyte Composition and Egress
A short-term exposure to moderately intense physical exercise affords a novel measure of protection against autoimmune-mediated peripheral nerve injury. Here, we investigated the mechanism by which forced exercise attenuates the development and progression of experimental autoimmune neuritis (EAN), an established animal model of Guillain–Barré syndrome. Adult male Lewis rats remained sedentary (control) or were preconditioned with forced exercise (1.2 km/day x 3 weeks) prior to P2-antigen induction of EAN. Sedentary rats developed a monophasic course of EAN beginning on postimmunization day 12.3 ± 0.2 a...
Source: ASN Neuro - July 17, 2015 Category: Neuroscience Authors: Calik, M. W., Shankarappa, S. A., Langert, K. A., Stubbs, E. B. Tags: Article Source Type: research
Epigenetic Modulation of Microglial Inflammatory Gene Loci in Helminth-Induced Immune Suppression: Implications for Immune Regulation in Neurocysticercosis
In neurocysticercosis, parasite-induced immune suppressive effects are thought to play an important role in enabling site-specific inhibition of inflammatory responses to infections. It is axiomatic that microglia-mediated (M1 proinflammatory) response causes central nervous system inflammation; however, the mechanisms by which helminth parasites modulate microglia activation remain poorly understood. Here, we show that microglia display a diminished expression of M1-inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nitric oxide synthase 2 (NOS2) in murine neurocysticercosi...
Source: ASN Neuro - July 6, 2015 Category: Neuroscience Authors: Chauhan, A., Quenum, F. Z., Abbas, A., Bradley, D. S., Nechaev, S., Singh, B. B., Sharma, J., Mishra, B. B. Tags: Original Article Source Type: research
Combined HDAC1 and HDAC2 Depletion Promotes Retinal Ganglion Cell Survival After Injury Through Reduction of p53 Target Gene Expression
Histones deacetylases (HDACs), besides their function as epigenetic regulators, deacetylate and critically regulate the activity of nonhistone targets. In particular, HDACs control partially the proapoptotic activity of p53 by balancing its acetylation state. HDAC inhibitors have revealed neuroprotective properties in different models, but the exact mechanisms of action remain poorly understood. We have generated a conditional knockout mouse model targeting retinal ganglion cells (RGCs) to investigate specifically the functional role of HDAC1 and HDAC2 in an acute model of optic nerve injury. Our results demonstrate that c...
Source: ASN Neuro - June 30, 2015 Category: Neuroscience Authors: Lebrun-Julien, F., Suter, U. Tags: Original Article Source Type: research
Ionizing Radiation Perturbs Cell Cycle Progression of Neural Precursors in the Subventricular Zone Without Affecting Their Long-Term Self-Renewal
We examined cellular and molecular changes associated with exposure of neural stem/progenitor cells (NSPs) to 137Cs -ray doses in the range of 0 to 8 Gy. Subventricular zone NSPs isolated from newborn mouse pups were analyzed for proliferation, self-renewal, and differentiation, shortly after irradiation. Strikingly, there was no apparent increase in the fraction of dying cells after irradiation, and the number of single cells that formed neurospheres showed no significant change from control. Upon differentiation, irradiated neural precursors did not differ in their ability to generate neurons, astrocytes, and oligodendro...
Source: ASN Neuro - June 8, 2015 Category: Neuroscience Authors: Chen, H., Goodus, M. T., de Toledo, S. M., Azzam, E. I., Levison, S. W., Souayah, N. Tags: Original Article Source Type: research
