Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines

Teeling, Jessica L.; Felton, Leigh M.; Deacon, Robert M. J.; Cunningham, Colm; Rawlins, J. N. P.; Perry, V. Hugh

doi:10.1016/j.bbi.2007.01.012

Cited by 130 publications

(104 citation statements)

References 66 publications

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“…The increasing risk of developing delirium in patients with a slightly increased IQCODE score might be explained by a vascular dysfunction or a reduced cholinergic activity, preceding the clinical mani-festations of dementia. Our findings are in accordance with the hypothesis of neuro-inflammation as a common pathophysiological mechanism of delirium and dementia, and the view that delirium may aggravate an ongoing neuro-inflammation [32][33][34] .…”

Section: Discussionsupporting

confidence: 80%

Delirium Is Not Associated with Mortality in Elderly Hip Fracture Patients

Juliebø

Krogseth²,

Skovlund³

et al. 2010

Dement Geriatr Cogn Disord

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Background: The relationship between delirium and mortality remains obscure. The aims of this study were to investigate the effect of delirium and the interaction between delirium and chronic cognitive impairment on mortality in elderly hip fracture patients. Methods: This is a prospective observational study, including 331 hip fracture patients. Information on comorbidity, medications and clinical findings was collected at the time of fracture. Information on cause and time of death was obtained from the Norwegian Cause of Death Register. Patients were screened for delirium by the Confusion Assessment Method. Results: Delirium was not associated with mortality when adjusting for the severity of chronic cognitive impairment, measured by the Infor- mant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Estimated by Kaplan-Meier plots, delirium in patients with dementia was significantly associated with an increased risk of death from stroke (p = 0.004) and dementia (p ≤ 0.001). Conclusions: No association between delirium and mortality was demonstrated when adjusting for the IQCODE score, but delirium in patients with prefracture dementia was associated with an increased risk of death from stroke and dementia. The effect of delirium on the cause of death might be explained by an aggravation of an ongoing neuro-inflammation.

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Section: Discussionsupporting

confidence: 80%

Delirium Is Not Associated with Mortality in Elderly Hip Fracture Patients

Juliebø

Krogseth²,

Skovlund³

et al. 2010

Dement Geriatr Cogn Disord

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“…Hippocampal lesioned mice often burrow less than 5 g 11 ( Figure 2). Prion disease inhibits burrowing 1,2 , as does lipopolysaccharide administration 20 . Burrowing can detect prion (scrapie) disease at 10-12 weeks after injection of diseased brain homogenate, whereas clinical signs only appear at 22 weeks 13 .…”

Section: Expected Resultsmentioning

confidence: 99%

Assessing Burrowing, Nest Construction, and Hoarding in Mice

Deacon

2012

JoVE

155

188

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Deterioration in the ability to perform "Activities of daily living" (ADL) is an early sign of Alzheimer's disease (AD). Preclinical behavioural screening of possible treatments for AD currently largely focuses on cognitive testing, which frequently demands expensive equipment and lots of experimenter time. However, human episodic memory (the most severely affected aspect of memory in AD) is different to rodent memory, which seems to be largely non-episodic. Therefore the present ways of screening for new AD treatments for AD in rodents are intrinsically unlikely to succeed. A new approach to preclinical screening would be to characterise the ADL of mice. Fortuitously, several such assays have recently been developed at Oxford, and here the three most sensitive and well-characterised are presented.Burrowing was first developed in Oxford 13. It evolved from a need to develop a mouse hoarding paradigm. Most published rodent hoarding paradigms required a distant food source to be linked to the home cage by a connecting passage. This would involve modifying the home cage as well as making a mouse-proof connecting passage and food source. So it was considered whether it would be possible to put the food source inside the cage. It was found that if a container was placed on the floor it was emptied by the next morning., The food pellets were, however, simply deposited in a heap at the container entrance, rather than placed in a discrete place away from the container, as might be expected if the mice were truly hoarding them. Close inspection showed that the mice were performing digging ("burrowing") movements, not carrying the pellets in their mouths to a selected place as they would if truly hoarding them.

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“…Compared to models of acute infection, rats with tumors (i.e., chronic disease) do not exhibit sickness behavior, and we infer that longer intervals of relatively modest increases in peripheral and central cytokine production must exist. Prolonged exposure to modest elevations in cytokines has been shown to induce anxiety-like behaviors in rodents (32,33) and learning deficits and emotional behavior in humans (34)(35)(36). Low magnitude increases in cytokine production over time frames typical of tumor formation (weeks to months) may be sufficient to mediate changes in affective states.…”

Section: Discussionmentioning

confidence: 99%

Peripheral tumors induce depressive-like behaviors and cytokine production and alter hypothalamic-pituitary-adrenal axis regulation

Pyter

Pineros

Galang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

117

107

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A strong and positive correlation exists between chronic disease and affective disorders, but the biological mechanisms underlying this relationship are not known. Here we show that rats with mammary cancer exhibit depression-and anxiety-like behaviors in the absence of overt sickness behaviors. The production of proinflammatory cytokines, known to induce depressive-like behaviors, was elevated in the periphery and in the hippocampus of rats with tumors compared with controls. In tumor-bearing rats, circulating corticosterone, which inhibits cytokine signaling, was suppressed following a stressor, and gene expression of hippocampal glucocorticoid receptors was elevated. The results establish that tumors alone are sufficient to trigger changes in emotional behaviors. Dampened glucocorticoid responses to stressors may exacerbate the deleterious effects of tumor-induced cytokines on affective states.cancer ͉ depression ͉ HPA ͉ hippocampus P hysical and psychological health share a bidirectional relationship (1-4). Individuals suffering from major peripheral illnesses (e.g., cancer, cardiovascular disease, AIDS, etc.) are at greater risk for depression and anxiety disorders relative to the healthy population (5-7). For example, mood disorders are reported in up to 60% of breast cancer patients (8-10). Co-morbid depression is associated with decreased cancer survivorship (11) and increased treatment noncompliance (12); therefore, understanding the mechanisms underlying cancer-associated depression is of profound clinical significance. Despite the strong association between cancer and mood disorders, the respective contributions of: (i) subjective disease awareness, (ii) toxic side-effects of chemotherapy, and (iii) direct biological effects of tumors in the pathogenesis of cancerassociated affective disorders have remained largely unexamined and undifferentiated (13)(14)(15).Tumor cells secrete cytokines and chemokines locally (16,17). Proinflammatory cytokines (primarily IL-1␤, IL-6, and TNF␣) induce depressive-like behavior (e.g., anhedonia, anorexia, lethargy) (18) via humoral and neural signaling from the periphery to the brain (19). The overwhelming majority of data relating peripheral proinflammatory cytokine production to alterations in behavior and affective states are generated using acute bacterial infection models (18, 19), not chronic disease models. Information on the effects of tumors or tumor-induced cytokines on behavior, on the other hand, is limited to the study of cancer-induced anorexia or cachexia (20). Thus, the hypothesis that tumor-derived cytokines contribute to cancer-induced depression has never been examined.Cytokine signaling can be regulated by neuroendocrine activity, principally through the production of glucocorticoids (21). Corticosterone suppresses the synthesis and actions of proinflammatory cytokines and can thereby inhibit the effects of proinflammatory cytokines on depressive-like behaviors (22-25). Because glucocorticoid production changes during progression of chronic disease ...

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Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines

Cited by 130 publications

References 66 publications

Delirium Is Not Associated with Mortality in Elderly Hip Fracture Patients

Delirium Is Not Associated with Mortality in Elderly Hip Fracture Patients

Assessing Burrowing, Nest Construction, and Hoarding in Mice

Peripheral tumors induce depressive-like behaviors and cytokine production and alter hypothalamic-pituitary-adrenal axis regulation

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