Food avoidance learning based on entirely voluntary wheel running in laboratory mice (Mus musculus)

Although it has been established that some acute phase responses present differently depending on whether a virus or bacteria activates the innate immune system, it has not yet been established whether fever and sickness behaviors, such as anorexia and lethargy, present differently. We therefore investigated the effects of administering lipopolysaccharide (LPS) and polyinosinic : polycytidylic acid (poly I:C) on body temperature, food intake, body mass, and activity (cage activity and wheel running). Male Sprague–Dawley rats were randomly assigned to receive an intraperitoneal injection of one of LPS (75 µg/kg or 250 µg/kg), poly I:C (3000 µg/kg or 4000 µg/kg), or saline. Administration of LPS or poly I:C induced fever, anorexia, and lethargy. Although voluntary wheel running and cage activity were both significantly reduced after administration of LPS or poly I:C, they were not affected equally. Indeed voluntary wheel running was decreased on average by approximately 30% more than cage activity regardless of the dose or type of mimetic administered. Our results indicate that poly I:C is less effective at inducing anorexia, lethargy, and fever in rats than is LPS, and that avoidance of exercise in animals and humans during infection is likely to be a more prominent feature of illness than is avoidance of routine daily activity.

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Abstract 12231: PECAM1 is Essential for Flow-mediated Gab1 Tyrosine Phosphorylation and Signaling in vitro and in vivo

Circulation ◽

10.1161/circ.132.suppl_3.12231 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Suowen Xu ◽

Marina Koroleva ◽

Keigi Fujiwara ◽

Zheng Gen Jin

Keyword(s):

Tyrosine Phosphorylation ◽

Wheel Running ◽

Tyrosine Phosphatase ◽

Common Mechanism ◽

Membrane Localization ◽

No Production ◽

Voluntary Wheel Running ◽

Voluntary Wheel

Introduction: Impaired activation of endothelial nitric oxide (NO) synthase (eNOS) and ensued NO production is a common mechanism of various cardiovascular pathologies, including hypertension and atherosclerosis. Specific signaling cascades, generated by vascular endothelial cells (ECs) in response to laminar flow, modulate EC structure and functions, NO production in particular. We have previously shown that flow-stimulated Gab1 (Grb2-associated binder-1) tyrosine phosphorylation mediates eNOS activation. However, the upstream mechanism that regulates Gab1 tyrosine phosphorylation remains unclear. Hypothesis: We hypothesized that platelet endothelial cell adhesion molecule-1 (PECAM1), a key molecule in an endothelial mechanosensing complex, specifically mediates Gab1 tyrosine phosphorylation and its downstream Akt and eNOS activation in ECs upon flow rather than hepatocyte growth factor (HGF) stimulation. Methods: Western blot, en face staining and voluntary wheel running. Results: Small interfering RNA (siRNA) targeting PECAM1 abolished flow- but not HGF-induced Gab1 tyrosine phosphorylation and Akt, eNOS activation as well as Gab1 membrane translocation. Protein-tyrosine phosphatase SHP2, which has been shown to interact with Gab1, was involved in a flow signaling pathway as well as HGF-induced signaling, as SHP2 siRNA diminished the flow- and HGF-induced Gab1 tyrosine phosphorylation, membrane localization and downstream signaling. Pharmacological inhibition of PI3K by LY294002 decreased flow, but not HGF-mediated Gab1 phosphorylation and membrane localization as well as eNOS activation. Finally, we observed that flow-mediated Gab1 and eNOS phosphorylation in vivo induced by voluntary wheel running was reduced in PECAM1 knockout mice. Conclusions: These results demonstrate a specific role of PECAM1 in flow-mediated Gab1 tyrosine phosphorylation and eNOS signaling in ECs

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