title: Glutamate release machinery is altered in the frontal cortex of rats with experimental autoimmune encephalomyelitis.
abstract: 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.
authors.affiliation: Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC, CONICET-UNC), Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, X5000HUA, Córdoba, Argentina.
authors.forename: Natalí L
authors.initials: NL
authors.lastname: Chanaday
authors.forename: A Alejandro
authors.initials: AA
authors.lastname: Vilcaes
authors.forename: Ana L
authors.initials: AL
authors.lastname: de Paul
authors.forename: Alicia I
authors.initials: AI
authors.lastname: Torres
authors.forename: Alicia L
authors.initials: AL
authors.lastname: Degano
authors.forename: German A
authors.initials: GA
authors.lastname: Roth
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D017208:Rats, Wistar; D016704:Synapsins / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016704:Synapsins; D018698:Glutamic Acid