Myelin Abnormalities in the Optic and Sciatic Nerves in Mice With GM1-Gangliosidosis
GM1-gangliosidosis is a glycosphingolipid lysosomal storage disease involving accumulation of GM1 and its asialo form (GA1) primarily in the brain. Thin-layer chromatography and X-ray diffraction were used to analyze the lipid content/composition and the myelin structure of the optic and sciatic nerves from 7- and 10-month old β-galactosidase (β-gal) +/? and β-gal –/– mice, a model of GM1gangliosidosis. Optic nerve weight was lower in the β-gal –/– mice than in unaffected β-gal +/? mice, but no difference was seen in sciatic nerve weight. The levels of GM1 and GA1 were signi...
Source: ASN Neuro - February 18, 2015 Category: Neuroscience Authors: Heinecke, K. A., Luoma, A., d'Azzo, A., Kirschner, D. A., Seyfried, T. N. Tags: Original Article Source Type: research
Nutrition Facts in Multiple Sclerosis
The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style...
Source: ASN Neuro - February 18, 2015 Category: Neuroscience Authors: Riccio, P., Rossano, R. Tags: Review Source Type: research
Internalization and Axonal Transport of the HIV Glycoprotein gp120
The HIV glycoprotein gp120, a neurotoxic HIV glycoprotein that is overproduced and shed by HIV-infected macrophages, is associated with neurological complications of HIV such as distal sensory polyneuropathy, but interactions of gp120 in the peripheral nervous system remain to be characterized. Here, we demonstrate internalization of extracellular gp120 in a manner partially independent of binding to its coreceptor CXCR4 by F11 neuroblastoma cells and cultured dorsal root ganglion neurons. Immunocytochemical and pharmacological experiments indicate that gp120 does not undergo trafficking through the endolysosomal pathway. ...
Source: ASN Neuro - January 30, 2015 Category: Neuroscience Authors: Berth, S., Caicedo, H. H., Sarma, T., Morfini, G., Brady, S. T. Tags: Original Article Source Type: research
Brain-Derived Neurotrophic Factor Deficiency Restricts Proliferation of Oligodendrocyte Progenitors Following Cuprizone-Induced Demyelination
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that through its neurotrophic tyrosine kinase, receptor, type 2 (TrkB) receptor, increases 5-bromo-2-deoxyuridine incorporation in oligodendrocyte progenitor cells (OPCs) in culture. Roles in vivo are less well understood; however, increases in numbers of OPCs are restricted in BDNF+/– mice following cuprizone-elicited demyelination. Here, we investigate whether these blunted increases in OPCs are associated with changes in proliferation. BDNF+/+ and BDNF+/– mice were fed cuprizone-containing or control feed. ...
Source: ASN Neuro - January 13, 2015 Category: Neuroscience Authors: Tsiperson, V., Huang, Y., Bagayogo, I., Song, Y., VonDran, M. W., DiCicco-Bloom, E., Dreyfus, C. F. Tags: Original Article Source Type: research
Connecting the Retina to the Brain
The visual system is beautifully crafted to transmit information of the external world to visual processing and cognitive centers in the brain. For visual information to be relayed to the brain, a series of axon pathfinding events must take place to ensure that the axons of retinal ganglion cells, the only neuronal cell type in the retina that sends axons out of the retina, find their way out of the eye to connect with targets in the brain. In the past few decades, the power of molecular and genetic tools, including the generation of genetically manipulated mouse lines, have multiplied our knowledge about the molecular mec...
Source: ASN Neuro - December 12, 2014 Category: Neuroscience Authors: Erskine, L., Herrera, E. Tags: Review Source Type: research
Hypothermia Modulates Cytokine Responses After Neonatal Rat Hypoxic-Ischemic Injury and Reduces Brain Damage
We examined ischemic core/penumbra and cytokine/chemokine evolution in a 10-day-old rat pup model of HII. Pups were treated for 24 hr after HII with HT (32℃; n = 18) or normothermia (NT, 35℃; n = 15). Outcomes included magnetic resonance imaging (MRI), neurobehavioral testing, and brain cytokine/chemokine profiling (0, 24, 48, and 72 hr post-HII). Lesion volumes (24 hr) were reduced in HT pups (total 74%, p < .05; penumbra 68%, p < .05; core 85%, p = .19). Lesion volumes rebounded at 72 hr (48 hr post-HT) with no significant differences between NT and HT pups. HT reduced interleukin-1β (IL-1β)...
Source: ASN Neuro - November 24, 2014 Category: Neuroscience Authors: Yuan, X., Ghosh, N., McFadden, B., Tone, B., Bellinger, D. L., Obenaus, A., Ashwal, S. Tags: Original Article Source Type: research
Convergent Regulation of Neuronal Differentiation and Erk and Akt Kinases in Human Neural Progenitor Cells by Lysophosphatidic Acid, Sphingosine 1-Phosphate, and LIF: Specific Roles for the LPA1 Receptor
The bioactive lysophospholipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) have diverse effects on the developing nervous system and neural progenitors, but the molecular basis for their pleiotropic effects is poorly understood. We previously defined LPA and S1P signaling in proliferating human neural progenitor (hNP) cells, and the current study investigates their role in neuronal differentiation of these cells. Differentiation in the presence of LPA or S1P significantly enhanced cell survival and decreased expression of neuronal markers. Further, the LPA receptor antagonist Ki16425 fully blocked the ef...
Source: ASN Neuro - November 24, 2014 Category: Neuroscience Authors: Callihan, P., Ali, M. W., Salazar, H., Quach, N., Wu, X., Stice, S. L., Hooks, S. B. Tags: Original Article Source Type: research
Both Creatine and Its Product Phosphocreatine Reduce Oxidative Stress and Afford Neuroprotection in an In Vitro Parkinson's Model
In conclusion, creatine and PCr minimize oxidative stress in striatum to afford neuroprotection of dopaminergic neurons. (Source: ASN Neuro)
Source: ASN Neuro - November 24, 2014 Category: Neuroscience Authors: Cunha, M. P., Martin-de-Saavedra, M. D., Romero, A., Egea, J., Ludka, F. K., Tasca, C. I., Farina, M., Rodrigues, A. L. S., Lopez, M. G. Tags: Original Article Source Type: research
Pre- and Posttreatment With Edaravone Protects CA1 Hippocampus and Enhances Neurogenesis in the Subgranular Zone of Dentate Gyrus After Transient Global Cerebral Ischemia in Rats
Edaravone is clinically used for treatment of patients with acute cerebral infarction. However, the effect of double application of edaravone on neurogenesis in the hippocampus following ischemia remains unknown. In the present study, we explored whether pre- and posttreatment of edaravone had any effect on neural stem/progenitor cells (NSPCs) in the subgranular zone of hippocampus in a rat model of transient global cerebral ischemia and elucidated the potential mechanism of its effects. Male Sprague-Dawley rats were divided into three groups: sham-operated (n = 15), control (n = 15), and edaravone-treated (n = 15) groups....
Source: ASN Neuro - November 11, 2014 Category: Neuroscience Authors: Lei, S., Zhang, P., Li, W., Gao, M., He, X., Zheng, J., Li, X., Wang, X., Wang, N., Zhang, J., Qi, C., Lu, H., Chen, X., Liu, Y. Tags: Original Article Source Type: research
Dietary Sutherlandia and Elderberry Mitigate Cerebral Ischemia-Induced Neuronal Damage and Attenuate p47phox and Phospho-ERK1/2 Expression in Microglial Cells
In this study, C57BL/6 J male mice were fed AIN93G diets without or with Sutherlandia or American elderberry for 2 months prior to a 30-min global cerebral ischemia induced by occlusion of the bilateral common carotid arteries (BCCAs), followed by reperfusion for 3 days. Accelerating rotarod assessment at 24 h after BCCA occlusion showed amelioration of sensorimotor impairment in the mice fed the supplemented diets as compared with the ischemic mice fed the control diet. Quantitative digital pathology assessment of brain slides stained with cresyl violet at ...
Source: ASN Neuro - October 16, 2014 Category: Neuroscience Authors: Chuang, D. Y., Cui, J., Simonyi, A., Engel, V. A., Chen, S., Fritsche, K. L., Thomas, A. L., Applequist, W. L., Folk, W. R., Lubahn, D. B., Sun, A. Y., Sun, G. Y., Gu, Z. Tags: Original Article Source Type: research
Dietary Sutherlandia and Elderberry Mitigate Cerebral Ischemia-Induced Neuronal Damage and Attenuate p47phox and Phospho-ERK1/2 Expression in Microglial Cells
In this study, C57BL/6 J male mice were fed AIN93G diets without or with Sutherlandia or American elderberry for 2 months prior to a 30-min global cerebral ischemia induced by occlusion of the bilateral common carotid arteries (BCCAs), followed by reperfusion for 3 days. Accelerating rotarod assessment at 24 h after BCCA occlusion showed amelioration of sensorimotor impairment in the mice fed the supplemented diets as compared with the ischemic mice fed the control diet. Quantitative digital pathology assessment of brain slides stained with cresyl violet at 3 days after ischemia/reperfusion (I/R) revealed significant reduc...
Source: ASN Neuro - October 16, 2014 Category: Neuroscience Authors: Chuang, D. Y., Cui, J., Simonyi, A., Engel, V. A., Chen, S., Fritsche, K. L., Thomas, A. L., Applequist, W. L., Folk, W. R., Lubahn, D. B., Sun, A. Y., Sun, G. Y., Gu, Z. Tags: Original Article Source Type: research
A New Model of Cuprizone-Mediated Demyelination/Remyelination
In the central nervous system, demyelinating diseases, such as multiple sclerosis, result in devastating long-term neurologic damage, in part because of the lack of effective remyelination in the adult human brain. One model used to understand the mechanisms regulating remyelination is cuprizone-induced demyelination, which allows investigation of remyelination mechanisms in adult animals following toxin-induced demyelination. Unfortunately, the degree of demyelination in the cuprizone model can vary, which complicates understanding the process of remyelination. Previous work in our laboratory demonstrated that the Akt/mTO...
Source: ASN Neuro - September 30, 2014 Category: Neuroscience Authors: Sachs, H. H., Bercury, K. K., Popescu, D. C., Narayanan, S. P., Macklin, W. B. Tags: Original Article Source Type: research
p75NTR, but Not proNGF, Is Upregulated Following Status Epilepticus in Mice
ProNGF and p75NTR are upregulated and induce cell death following status epilepticus (SE) in rats. However, less is known about the proneurotrophin response to SE in mice, a more genetically tractable species where mechanisms can be more readily dissected. We evaluated the temporal- and cell-specific induction of the proneurotrophins and their receptors, including p75NTR, sortilin, and sorCS2, following mild SE induced with kainic acid (KA) or severe SE induced by pilocarpine. We found that mature NGF, p75NTR, and proBDNF were upregulated following SE, while proNGF was not altered, indicating potential mechanistic differen...
Source: ASN Neuro - September 25, 2014 Category: Neuroscience Authors: VonDran, M. W., LaFrancois, J., Padow, V. A., Friedman, W. J., Scharfman, H. E., Milner, T. A., Hempstead, B. L. Tags: Original Article Source Type: research
Cerebral Protein Synthesis in a Knockin Mouse Model of the Fragile X Premutation
The (CGG)n-repeat in the 5'-untranslated region of the fragile X mental retardation gene (FMR1) gene is polymorphic and may become unstable on transmission to the next generation. In fragile X syndrome, CGG repeat lengths exceed 200, resulting in silencing of FMR1 and absence of its protein product, fragile X mental retardation protein (FMRP). CGG repeat lengths between 55 and 200 occur in fragile X premutation (FXPM) carriers and have a high risk of expansion to a full mutation on maternal transmission. FXPM carriers have an increased risk for developing progressive neurodegenerative syndromes and neuropsychological sympt...
Source: ASN Neuro - September 23, 2014 Category: Neuroscience Authors: Qin, M., Huang, T., Liu, Z., Kader, M., Burlin, T., Xia, Z., Zeidler, Z., Hukema, R. K., Smith, C. B. Tags: Original Article Source Type: research
Comparison of Cortical and White Matter Traumatic Brain Injury Models Reveals Differential Effects in the Subventricular Zone and Divergent Sonic Hedgehog Signaling Pathways in Neuroblasts and Oligodendrocyte Progenitors
We examined whether Shh signaling contributes to neuroblast (doublecortin) or oligodendrocyte progenitor (neural/glial antigen 2 [NG2]) responses in two distinct TBI models. Shh-responsive cells were heritably labeled in vivo using Gli1-CreERT2;R26-YFP bitransgenic mice with tamoxifen administration on Days 2 and 3 post-TBI. Injury to the cerebral cortex was produced with mild controlled cortical impact. Yellow fluorescent protein (YFP) cells decreased in cortical lesions. Total YFP cells increased in the subventricular zone (SVZ), indicating Shh pathway activation in SVZ cells, including doublecortin-labeled neurobla...
Source: ASN Neuro - September 23, 2014 Category: Neuroscience Authors: Mierzwa, A. J., Sullivan, G. M., Beer, L. A., Ahn, S., Armstrong, R. C. Tags: Original Article Source Type: research
