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

JiaJia Wang, YanJun Li, Ke Lai, QiMei Zhong, Konstantin A Demin, Allan V. Kalueff, Cai Song

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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 anxiety-like behavior in the novel tank and light-dark box (Days 15-16) tests, as well as examined their 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-gamma and IL-4, as well as higher brain mRNA expression of the glucocorticoid receptor, CD11b (a microglial biomarker), pro-inflammatory cytokines IL-6 and TNF-alpha (but not IL-1 beta or anti-inflammatory cytokines IL-4 and IL-10), GFAP (an astrocytal biomarker), neurotrophin BDNF, its receptors p75 and 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.

Original languageEnglish
Article number109752
Number of pages7
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Early online date22 Aug 2019
StatePublished - 10 Jan 2020

Scopus subject areas

  • Biological Psychiatry
  • Pharmacology


  • Affective disorders
  • Microglia
  • Neuroinflammation
  • Type 2 diabetes
  • Zebrafish
  • RISK


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