However, after peripheral challenge with a low dose of LPS, Pink1−/− mice expressed higher levels of IL-1β, IL-12 and IL-10 in the striatum compared to wildtype mice (Fig. 8A).
As main findings, we demonstrate that prion strain divergence can occur upon transmission of human, primary vCJD to such mice, and that peripheral challenge leads to an asymptomatic, life-long infection of the lymphoid compartment.
An increase in fluorescence detection of spatially localized intrahippocampal IL-1β release was observed following a peripheral lipopolysaccharide challenge in Sprague-Dawley rats.
This chemokine is an important regulator of brain inflammation following a peripheral immune challenge [ 59, 60].
However, previous work has shown that neuroinflammatory responses to a peripheral immune challenge are brain region specific [ 64– 64].
This brain structure is associated with depression and has previously been shown to display immune cell activation following a peripheral immune challenge [ 27, 67, 68].
This TNF- α-induced astrocyte activation occurred after the peak release of proinflammatory cytokines and lasted for 2 days, thereby suggesting that the brain sequelae to a peripheral immune challenge may propagate in absence of the initial stimulus.
Our findings suggest the regional lymph node as a potentially facilitating or even essential factor for invasion of the brain after peripheral challenge with low doses of infectious scrapie agent.
In some way this operation annihilates the effects discussed above in terms of peripheral challenge and de-concentration.
Indeed, apart from a recent report describing the detection of abnormal PrP in splenic follicular cells of knock-in mice expressing a mouse/human PrP chimera within months after vCJD infection [20], there are no published data regarding the fate of infection after peripheral challenge, or the propagation of prions in extraneural tissues.
Moreover, Pink1−/− mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1−/− embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity.
