Clin Psychopharmacol Neurosci.  2018 Nov;16(4):422-433. 10.9758/cpn.2018.16.4.422.

From Gut to Brain: Alteration in Inflammation Markers in the Brain of Dextran Sodium Sulfate-induced Colitis Model Mice

• Do J
• Woo J

• KMID: 2428972
• DOI: http://doi.org/10.9758/cpn.2018.16.4.422

Abstract

OBJECTIVE
Neuropsychiatric manifestations like depression and cognitive dysfunction commonly occur in inflammatory bowel disease (IBD). In the context of the brain-gut axis model, colitis can lead to alteration of brain function in a bottom-up manner. Here, the changes in the response of the hypothalamic-pituitary-adrenal axis and inflammation-related markers in the brain in colitis were studied.
METHODS
Dextran sodium sulfate (DSS) was used to generate a mouse model of colitis. Mice were treated with DSS for 3 or 7 days and sacrificed. We analyzed the gene expression of brain-derived neurotrophic factor (BDNF), cyclo-oxygenase 2 (COX-2), and glial fibrillary acidic protein (GFAP), and the expression of GFAP, in the hippocampus, hypothalamus, and amygdala. Additionally, the levels of C-reactive protein (CRP) and serum cortisol/corticosterone were measured.
RESULTS
Alteration of inflammatory-related markers varied depending on the brain region and exposure time. In the hippocampus, COX-2 mRNA, GFAP mRNA, and GFAP expression were upregulated during exposure to DSS. However, in the hypothalamus, COX-2 mRNA was upregulated only 3 days after treatment. In the amygdala, BDNF and COX-2 mRNAs were downregulated. CRP and corticosterone expression increased with DSS treatment at day 7.
CONCLUSION
IBD could lead to neuroinflammation in a bottom-up manner, and this effect varied according to brain region. Stress-related hormones and serum inflammatory markers, such as CRP, were upregulated from the third day of DSS treatment. Therefore, early and active intervention is required to prevent psychological and behavioral changes caused by IBD, and region-specific studies can help understand the precise mechanisms by which IBD affects the brain.

Keyword

Inflammatory bowel disease; Dextran sodium sulfate; Neuroinfalmmation; Cyclooxygenase 2; Glial fibrillary acidic protein; Brain-derived neurotrophic factor

MeSH Terms

Amygdala
Animals
Brain*
Brain-Derived Neurotrophic Factor
C-Reactive Protein
Colitis*
Corticosterone
Cyclooxygenase 2
Depression
Dextrans*
Gene Expression
Glial Fibrillary Acidic Protein
Hippocampus
Hypothalamus
Inflammation*
Inflammatory Bowel Diseases
Mice*
Prostaglandin-Endoperoxide Synthases
RNA, Messenger
Sodium*
Brain-Derived Neurotrophic Factor
C-Reactive Protein
Corticosterone
Cyclooxygenase 2
Dextrans
Glial Fibrillary Acidic Protein
Prostaglandin-Endoperoxide Synthases
RNA, Messenger
Sodium