PUBLICATION

High-glucose/high-cholesterol diet in zebrafish evokes diabetic and affective pathogenesis: The role of peripheral and central inflammation, microglia and apoptosis

Authors
Wang, J., Li, Y., Lai, K., Zhong, Q., Demin, K.A., Kalueff, A.V., Song, C.
ID
ZDB-PUB-190826-27
Date
2019
Source
Progress in neuro-psychopharmacology & biological psychiatry   96: 109752 (Journal)
Registered Authors
Kalueff, Allan V.
Keywords
Affective disorders, Microglia, Neuroinflammation, Type 2 diabetes, Zebrafish
MeSH Terms
  • Animals
  • Apoptosis/drug effects
  • Apoptosis/physiology*
  • Cholesterol, Dietary/adverse effects
  • Cholesterol, Dietary/toxicity*
  • Diabetes Mellitus, Experimental/chemically induced
  • Diabetes Mellitus, Experimental/metabolism*
  • Diabetes Mellitus, Type 2/chemically induced
  • Diabetes Mellitus, Type 2/metabolism
  • Female
  • Glucose/administration & dosage
  • Glucose/toxicity*
  • Inflammation Mediators/metabolism*
  • Male
  • Microglia/drug effects
  • Microglia/metabolism*
  • Zebrafish
PubMed
31446160 Full text @ Prog. Neuropsychopharmacol. Biol. Psychiatry
Abstract
Neuroinflammation and metabolic deficits contribute to the etiology of human affective disorders, such as anxiety and depression. The zebrafish (Danio rerio) has recently emerged as a powerful new model organism in CNS disease modeling. Here, we exposed zebrafish to 2% glucose and 10% cholesterol for 19 days to experimentally induce type 2 diabetes (DM) and to assess stress responses, microglia, inflammation and apoptosis. We analyzed zebrafish behavior in the novel tank and light-dark box (Days 15-16) tests, as well as biochemical and genomic biomarkers (Day 19). Confirming DM-like state in zebrafish, we found higher whole-body glucose, triglyceride, total cholesterol, low-density lipoprotein levels and glucagon mRNA expression, and lower high-density lipoprotein levels. DM zebrafish also showed anxiety-like behavior, elevated whole-body cortisol and cytokines IFN-γ and IL-4, as well as higher brain mRNA expression of the glucocorticoid receptor, CD11b (a microglial biomarker), pro-inflammatory cytokines IL-6, IL-6R and TNF-α (but not IL-1β or anti-inflammatory cytokines IL-4 and IL-10), GFAP (an astrocyte biomarker), neurotrophin BDNF, its receptor p75 (but not TrkB), as well as apoptotic Bax and Caspase-3 (but not BCl-2) genes. Collectively, this supports the overlapping nature of DM-related affective pathogenesis and emphasizes the role of peripheral and central inflammation and apoptosis in DM-related affective and neuroendocrine deficits in zebrafish.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping