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Peripheral infections in mammals are characterised by local, systemic and CNS effects. The latter give rise to sickness behaviour. Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) are thought to be important mediators of this neuro-immune signalling (Cartmell et al., 1999). There is anecdotal evidence suggesting that peripheral infections in(More)
The contribution of inflammation to the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's, and prion diseases is poorly understood. Brain inflammation in animal models of these diseases is dominated by chronic microglial activation with minimal proinflammatory cytokine expression. However, these inflammatory cells are "primed" to(More)
Mouse-adapted scrapie strains have been characterized by vacuolation profiles and incubation times, but the behavioral consequences have not been well studied. Here, we compared behavioral impairments produced by ME7, 79A, 22L, and 22A strains in C57BL/6J mice. We show that early impairments on burrowing, glucose consumption, nesting and open field(More)
Systemic inflammation impacts on the brain and gives rise to behavioral changes, often referred to as 'sickness behavior'. These symptoms are thought to be mainly mediated by pro-inflammatory cytokines. We have investigated the communication pathways between the immune system and brain following sub-pyrogenic inflammation. Low grade systemic inflammation(More)
Poor maternal nutrition during pregnancy can alter postnatal phenotype and increase susceptibility to adult cardiovascular and metabolic diseases. However, underlying mechanisms are largely unknown. Here, we show that maternal low protein diet (LPD), fed exclusively during mouse preimplantation development, leads to offspring with increased weight from(More)
Delirium is an acute, severe neuropsychiatric syndrome, characterized by cognitive deficits, that is highly prevalent in aging and dementia and is frequently precipitated by peripheral infections. Delirium is poorly understood and the lack of biologically relevant animal models has limited basic research. Here we hypothesized that synaptic loss and(More)
It is well known that systemic infections cause flare-ups of disease in individuals with asthma and rheumatoid arthritis, and that relapses in multiple sclerosis can often be associated with upper respiratory-tract infections. Here we review evidence to support our hypothesis that in chronic neurodegenerative diseases such as Alzheimer's disease, with an(More)
BACKGROUND Chronic neurodegeneration results in microglial activation, but the contribution of inflammation to the progress of neurodegeneration remains unclear. We have shown that microglia express low levels of proinflammatory cytokines during chronic neurodegeneration but are "primed" to produce a more proinflammatory profile after systemic challenge(More)
Systemic inflammation gives rise to metabolic and behavioural changes, largely mediated by pro-inflammatory cytokines and prostaglandin production (PGE(2)) at the blood-brain barrier. Despite numerous studies, the exact biological pathways that give rise to these changes remains elusive. This study investigated the mechanisms underlying immune-to-brain(More)
The role of inflammation in the progression of neurodegenerative disease remains unclear. We have shown that systemic bacterial insults accelerate disease progression in animals and in patients with Alzheimer's disease. Disease exacerbation is associated with exaggerated CNS inflammatory responses to systemic inflammation mediated by microglia that become(More)