Hypothalamic TLR2 triggers sickness behavior via a microglianeuronal axis

被引：72

作者：

Jin, Sungho ^{[1
]}

Kim, Jae Geun ^{[2
,3
]}

Park, Jeong Woo ^{[1
]}

Koch, Marco ^{[3
,4
]}

Horvath, Tamas L. ^{[3
]}

Lee, Byung Ju ^{[1
]}

机构：

[1] Univ Ulsan, Dept Biol Sci, Ulsan 680749, South Korea

[2] Incheon Natl Univ, Coll Life Sci & Bioengn, Div Life Sci, Inchon 406772, South Korea

[3] Yale Univ, Sch Med, Comparat Med Sect, Program Integrat Cell Signaling & Neurobiol Metab, New Haven, CT 06520 USA

[4] Univ Leipzig, Inst Anat, D-04103 Leipzig, Germany

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

基金：

新加坡国家研究基金会;

关键词：

TOLL-LIKE RECEPTORS; NF-KAPPA-B; BLOOD-BRAIN-BARRIER; ACTIVATION; EXPRESSION; NEURONS; IMMUNE; BETA; OLIGODENDROGENESIS; NEUROPROTECTION;

D O I：

10.1038/srep29424

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Various pathophysiologic mechanisms leading to sickness behaviors have been proposed. For example, an inflammatory process in the hypothalamus has been implicated, but the signaling modalities that involve inflammatory mechanisms and neuronal circuit functions are ill-defined. Here, we show that toll-like receptor 2 (TLR2) activation by intracerebroventricular injection of its ligand, Pam3CSK4, triggered hypothalamic inflammation and activation of arcuate nucleus microglia, resulting in altered input organization and increased activity of proopiomelanocortin (POMC) neurons. These animals developed sickness behavior symptoms, including anorexia, hypoactivity, and hyperthermia. Antagonists of nuclear factor kappa B (NF-kappa B), cyclooxygenase pathway and melanocortin receptors 3/4 reversed the anorexia and body weight loss induced by TLR2 activation. These results unmask an important role of TLR2 in the development of sickness behaviors via stimulation of hypothalamic microglia to promote POMC neuronal activation in association with hypothalamic inflammation.

引用

页数：13

共 51 条

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