Tollip, an early regulator of the acute inflammatory response in the substantia nigra.

Tollip is a ubiquitously expressed protein, originally described as a modulator of the IL-1R/TLR-NF-κB signaling pathways. Although this property has been well characterized in peripheral cells, and despite some evidence of its expression in the central nervous system, the role of Tollip in neuroinflammation remains poorly understood. The present study sought to explore the implication of Tollip in inflammation in the substantia nigra pars compacta, the structure affected in Parkinson's disease. We first investigated Tollip distribution in the midbrain by immunohistochemistry. Then, we addressed TLR4-mediated response by intra-nigral injections of lipopolysaccharide (LPS), a TLR4 agonist, on inflammatory markers in Tollip knockout (KO) and wild-type (WT) mice. We report an unexpectedly high Tollip immunostaining in dopaminergic neurons of the mice brain. Second, intra-nigral injection of LPS led to increased susceptibility to neuroinflammation in Tollip KO compared to Tollip WT mice. This was demonstrated by a significant increase of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and interferon gamma (IFN-γ) messenger RNA (mRNA) in the midbrain of Tollip KO mice upon LPS injection. Consistently, brain rAAV viral vector transduction with a nuclear factor kappa B (NF-κB)-inducible reporter gene confirmed increased NF-κB activation in Tollip KO mice. Lastly, Tollip KO mice displayed higher inducible NO synthase (iNOS) production, both at the messenger and protein level when compared to LPS-injected WT mice. Tollip deletion also aggravated LPS-induced oxidative and nitrosative damages, as indicated by an increase of 8-oxo-2'-deoxyguanosine and nitrotyrosine immunostaining, respectively. Altogether, these findings highlight a critical role of Tollip in the early phase of TLR4-mediated neuroinflammation. As brain inflammation is known to contribute to Parkinson's disease, Tollip may be a potential target for neuroprotection

Managing Performance Throughout Periods of Travel

Understanding the impact of travel on physical performance is an increasing area of interest for the strength and conditioning practitioner. Previous research surrounding the effect of travel on the physiology of an athlete has focused on sleep. Of concern to coaches and athletes are strategies to help attenuate any detrimental impact of travel on subsequent performance. The aim of this article is to provide informative practical guidelines for before, during, and after travel that can be implemented by coaches and athletes. The key coping strategies addressed include timed light exposure; managing sleep deprivation and nutritional recommendations

Additional file 4: Figure S4. of Tollip, an early regulator of the acute inflammatory response in the substantia nigra

No induction of iNOS 6 h after PBS injection in the midbrain of Tollip KO mice. A representative iNOS and NeuN immunostaining in the midbrain in contralateral and ipsilateral side of the PBS (1 μL) injection, in Tollip KO mice. Magnification = ×40. Scale bar = 30 μm. (TIF 740 kb