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

Результат исследований: Научные публикации в периодических изданияхстатьярецензирование

16 Цитирования (Scopus)

Аннотация

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.

Язык оригиналаанглийский
Номер статьи109752
Число страниц7
ЖурналProgress in Neuro-Psychopharmacology and Biological Psychiatry
Том96
Ранняя дата в режиме онлайн22 авг 2019
DOI
СостояниеОпубликовано - 10 янв 2020

Предметные области Scopus

  • Биологическая психиатрия
  • Фармакология

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