Glutamate Release Machinery Is Altered in the Frontal Cortex of Rats with Experimental Autoimmune Encephalomyelitis
| Autor: | Natali L. Chanaday, Ana L. De Paul, Aldo Alejandro Vilcaes, Alicia Inés Torres, German A. Roth, Alicia L. Degano |
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| Rok vydání: | 2014 |
| Předmět: |
RELEASE MACHINERY
Synapsin I Encephalomyelitis Autoimmune Experimental Encephalomyelitis Central nervous system Presynaptic Terminals Neuroscience (miscellaneous) Glutamic Acid SYNAPTOSOMES Biology Ciencias Biológicas Cellular and Molecular Neuroscience medicine Animals SYNAPTSIN Rats Wistar GLUTAMATE RELEASE Prefrontal cortex MULTIPLE SCLEROSIS Multiple sclerosis Experimental autoimmune encephalomyelitis Glutamate receptor Synapsin Bioquímica y Biología Molecular Synapsins medicine.disease Frontal Lobe medicine.anatomical_structure Neurology EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS Neuroscience CIENCIAS NATURALES Y EXACTAS Synaptosomes |
| Zdroj: | Molecular Neurobiology. 51:1353-1367 |
| ISSN: | 1559-1182 0893-7648 |
| Popis: | Experimental autoimmune encephalomyelitis (EAE) is an animal model that mimics many of the clinical and pathological features of the human disease multiple sclerosis (MS). Both are inflammatory demyelinating and neurodegenerative pathologies of the central nervous system associated with motor, sensory, and cognitive deficits. In MS, gray matter atrophy is related to the emergence of cognitive deficits and contributes to clinical progression. In particular, prefrontal cortex injury and dysfunction have been correlated to the development of fatigue, one of the most common and disabling symptoms in MS. However, the molecular bases of these changes remain unknown. Taking advantage of EAE similitude, we herein analyze functional and morphological changes in isolated cortical presynaptic terminals (synaptosomes) from an acute rat model. We found impaired glutamate release in the frontal cortex from EAE rats. This defect appeared along with the onset of the disease, reversing when clinical signs were no more evident. Biochemical analysis of EAE synaptosomes revealed alterations in the presynaptic release machinery and in the response to depolarization, which was accompanied by abnormal synapsin I phosphorylation and dispersion. These changes were associated with reduced synaptic vesicle mobility, with no alterations in synaptosomal morphology as evidenced by electron microscopy. The present are the first pieces of evidence unraveling the molecular mechanisms of frontal cortex neuronal dysfunction in EAE and, possibly, MS. Fil: Chanaday Ricagni, Natalí Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones En Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Quimica Biológica; Argentina Fil: Vilcaes, Aldo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones En Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Quimica Biológica; Argentina Fil: de Paul, Ana Lucia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina Fil: Torres, Alicia Ines. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina Fil: Degano, Alicia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones En Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Quimica Biológica; Argentina Fil: Roth, German Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones En Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Quimica Biológica; Argentina |
| Databáze: | OpenAIRE |
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