Inflammation Triggers Synaptic Alteration and Degeneration in Experimental Autoimmune Encephalomyelitis

被引：321

作者：

Centonze, Diego ^{[1
,2
]}

Muzio, Luca ^{[5
]}

Rossi, Silvia ^{[1
,2
]}

Cavasinni, Francesca ^{[5
]}

De Chiara, Valentina ^{[1
,2
]}

Bergami, Alessandra ^{[5
]}

Musella, Alessandra ^{[1
,2
]}

D'Amelio, Marcello ^{[3
]}

Cavallucci, Virve ^{[3
]}

Martorana, Alessandro ^{[1
]}

Bergamaschi, Andrea ^{[5
]}

Cencioni, Maria Teresa ^{[4
]}

Diamantini, Adamo ^{[4
]}

Butti, Erica ^{[5
]}

Comi, Giancarlo ^{[5
]}

Bernardi, Giorgio ^{[1
,2
]}

Cecconi, Francesco ^{[3
]}

Battistini, Luca ^{[4
]}

Furlan, Roberto ^{[5
]}

Martino, Gianvito ^{[5
]}

机构：

[1] Univ Roma Tor Vergata, Dept Neurosci, Neurol Clin, I-00133 Rome, Italy

[2] Santa Lucia Fdn, Ctr Europeo Ric Cervello, Lab Expt Neurol, I-00143 Rome, Italy

[3] Santa Lucia Fdn, Ctr Europeo Ric Cervello, Lab Mol Neuroembryol, I-00143 Rome, Italy

[4] Santa Lucia Fdn, Ctr Europeo Ric Cervello, Neuroimmunol Unit, I-00143 Rome, Italy

[5] Ist Sci San Raffaele, Inst Expt Neurol, Neuroimmunol Unit, I-20132 Milan, Italy

来源：

JOURNAL OF NEUROSCIENCE | 2009年 / 29卷 / 11期

关键词：

NECROSIS-FACTOR-ALPHA; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; METABOTROPIC GLUTAMATE RECEPTORS; GLIAL TNF-ALPHA; MULTIPLE-SCLEROSIS; AMPA RECEPTOR; EXPRESSION PATTERNS; CEREBROSPINAL-FLUID; ADULT NEUROGENESIS; ALTERED EXPRESSION;

D O I：

10.1523/JNEUROSCI.5804-08.2009

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Neurodegeneration is the irremediable pathological event occurring during chronic inflammatory diseases of the CNS. Here we show that, in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, inflammation is capable in enhancing glutamate transmission in the striatum and in promoting synaptic degeneration and dendritic spine loss. These alterations occur early in the disease course, are independent of demyelination, and are strongly associated with massive release of tumor necrosis factor-alpha from activated microglia. CNS invasion by myelin-specific blood-borne immune cells is the triggering event, and the downregulation of the early gene Arc/Arg3.1, leading to the abnormal expression and phosphorylation of AMPA receptors, represents a culminating step in this cascade of neurodegenerative events. Accordingly, EAE-induced synaptopathy subsided during pharmacological blockade of AMPA receptors. Our data establish a link between neuroinflammation and synaptic degeneration and calls for early neuroprotective therapies in chronic inflammatory diseases of the CNS.

引用

页码：3442 / 3452

页数：11

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