Format

Send to

Choose Destination
  • Showing results for systemic tnf a produced acute cognitive dysfunction and exaggerated sickness behavior when superimposed upon progressive neurodegeneration. Your search for Systemic TNF-a produces acute cognitive dysfunction and exaggerated sickness behavior when superimposed upon progressive neurodegeneration retrieved no results.
Brain Behav Immun. 2017 Jan;59:233-244. doi: 10.1016/j.bbi.2016.09.011. Epub 2016 Sep 12.

Systemic TNF-α produces acute cognitive dysfunction and exaggerated sickness behavior when superimposed upon progressive neurodegeneration.

Author information

1
School of Biochemistry & Immunology, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland.
2
School of Biochemistry & Immunology, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland. Electronic address: colm.cunningham@tcd.ie.

Abstract

Inflammation influences chronic neurodegeneration but its precise roles are not yet clear. Systemic inflammation caused by infection, trauma or co-morbidity can alter the brain's inflammatory status, produce acute cognitive impairments, such as delirium, and drive new pathology and accelerated decline. Consistent with this, elevated systemic TNF-α is associated with more rapid cognitive decline over 6months in Alzheimer's disease patients. In the current study we challenged normal animals and those with existing progressive neurodegeneration (ME7 prion disease) with TNF-α (i.p.) to test the hypothesis that this cytokine has differential effects on cognitive function, sickness behavior and features of underlying pathology contingent on the animals' baseline condition. TNF-α (50μg/kg) had no impact on performance of normal animals (normal brain homogenate; NBH) on working memory (T-maze) but produced acute impairments in ME7 animals similarly challenged. Plasma TNF-α and CCL2 levels were equivalent in NBH and ME7 TNF-challenged animals but hippocampal and hypothalamic transcription of IL-1β, TNF-α and CCL2 and translation of IL-1β were higher in ME7+TNF-α than NBH+TNF-α animals. TNFproduced an exaggerated sickness behavior response (hypothermia, weight loss, inactivity) in ME7 animals compared to that in NBH animals. However a single challenge with this dose was not sufficient to produce de novo neuronal death, synaptic loss or tau hyperphosphorylation that was distinguishable from that arising from ME7 alone. The data indicate that acutely elevated TNF-α has robust acute effects on brain function, selectively in the degenerating brain, but more sustained levels may be required to significantly impact on underlying neurodegeneration.

KEYWORDS:

Behavior; Delirium; Dementia; Microglia; Sickness; Systemic inflammation; TNF

PMID:
27633985
PMCID:
PMC5176008
DOI:
10.1016/j.bbi.2016.09.011
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center