This document describes a study investigating the relationship between colitis-induced inflammation in the gut and neuroinflammation in the brain. The study found that a mild acute colitis model resulted in a small, non-significant increase in microglia activation in the brain, but a more severe acute colitis model did not. In a chronic colitis model, some animals showed increased microglia activation in the brain while others did not, indicating variable responses. The results provide preliminary evidence that gut inflammation may be linked to neuroinflammation, but the relationship requires further investigation.
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Neuroinflammation Link Between Colitis and Brain Disease
1. Acute colitis (3% DSS) resulted in about a 20% increase in [11C]PK11195 uptake in the brain; the effect was not
significant. The PET data were confirmed with preliminary Iba-1 staining of activated microglia in the neocortex, which
showed a slight increase in microglia activation in the acute 3% DSS group compared to the other groups. However, in a
more severe acute model of colitis (5% DSS), we did not observe increased [11C]PK11195 uptake in the brain.
In the chronic model of colitis, we observed very variable responses to DSS treatment. Part of the animals showed
increased [11C]PK11195 uptake in the brain on day 36, whereas others did not show any effect at all.
Neuoinflammation (mainly represented by
activated microglia) plays a role in the
pathology of brain disease, including
depression1.
Epidemiological studies show increasing
incidence of depression in patients with colitis2.
Colitis is characterized by strong
inflammation in the gut. We hypothesize that
the inflammation in the gut may lead to
increased activation of microglia in the brain.
Introduction Methods
Neuroinflammation in a mouse model of colitis:
cross-talk between the gut and the brain.
Kurtys E1, Eisel ULM2, Boerema AS1, Kraneveld AD3, Broersen LM4 Dierckx RAJO1, de Vries EFJ1
1 Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen , The Netherlands, 2 Department of
Molecular Neurobiology, University of Groningen, Groningen, The Netherlands, 3 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science,
Utrecht University, Utrecht, The Netherlands 4 Nutricia Advanced Medical Nutrition, Nutricia Research, Utrecht, The Netherlands
contact: e.kurtys@umcg.nl
COLITIS
ACTIVATION
OF MICROGLIA
HYPOTHESIS:
Iba-1 staining
Results
Disease progression
- C57bl/6 male mice
- Colitis induced by DSS (dextran sodium
sulfate) administrated in drinking water in 5-
days cycles (1 cycle for the acute model
and 3 cycles for the chronic model)
Ref: 1. Maes et al., Metab Brain Dis. 2009; 24:27-53 2. Román et al, World J Gastroenterol, 2011; 17:2723-33 3. Ma et al, Neuroscience. 2005;135:1203-15 4. Ma et al, Front Neuroanat. 2008 Apr 17;2:1
Preliminary conclusions:
An example of SUV-PET image of
[11C]PK11195: transaxial (A), coronal (B)
and sagittal (C) view and their overlays with
MRI template of the whole brain (D-E).
[11C] PK11195 PET imaging