Loss of astrocytic leptin signaling worsens experimental autoimmune encephalomyelitis

被引:17
|
作者
Mishra, Pramod K. [1 ]
Hung Hsuchou [1 ]
Ouyang, Suidong [1 ]
Kastin, Abba J. [1 ]
Wu, Xiaojun [1 ]
Pan, Weihong [1 ]
机构
[1] Pennington Biomed Res Ctr, Blood Brain Barrier Grp, Baton Rouge, LA 70808 USA
关键词
EAE; Reactive astrogliosis; Leptin receptor; Neuroinflammation; Autoimmunity; Adenosine; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; DIET-INDUCED OBESITY; BLOOD-BRAIN-BARRIER; T-CELL RESPONSES; MULTIPLE-SCLEROSIS; UP-REGULATION; RECEPTOR MUTATION; INTERFERON-BETA; SPINAL-CORD;
D O I
10.1016/j.bbi.2013.07.176
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Leptin is commonly thought to play a detrimental role in exacerbating experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis. Paradoxically, we show here that astrocytic leptin signaling has beneficial effects in reducing disease severity. In the astrocyte specific leptin receptor knockout (ALKO) mouse in which leptin signaling is absent in astrocytes, there were higher EAE scores (more locomotor deficits) than in the wildtype counterparts. The difference mainly occurred at a late stage of EAE when wildtype mice showed signs of recovery whereas ALKO mice continued to deteriorate. The more severe symptoms in ALKO mice coincided with more infiltrating cells in the spinal cord and perivascular brain parenchyma, more demyelination, more infiltrating CD4 cells, and a lower percent of neutrophils in the spinal cord 28 days after EAR induction. Cultured astrocytes from wildtype mice showed increased adenosine release in response to interleukin-6 and the hippocampus of wildtype mice had increased adenosine production 28 days after EAE induction, but the ALKO mutation abolished the increase in both conditions. This indicates a role of astrocytic leptin in normal gliotransmitter release and astrocyte functions. The worsening of EAE in the ALKO mice in the late stage suggests that astrocytic leptin signaling helps to clear infiltrating leukocytes and reduce autoimmune destruction of the CNS. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:98 / 107
页数:10
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