TY - JOUR

T1 - High-glucose/high-cholesterol diet in zebrafish evokes diabetic and affective pathogenesis

T2 - The role of peripheral and central inflammation, microglia and apoptosis

AU - Wang, JiaJia

AU - Li, YanJun

AU - Lai, Ke

AU - Zhong, QiMei

AU - Demin, Konstantin A

AU - Kalueff, Allan V.

AU - Song, Cai

N1 - Copyright © 2019. Published by Elsevier Inc.

PY - 2020/1/10

Y1 - 2020/1/10

N2 - 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.

AB - 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.

KW - Affective disorders

KW - Microglia

KW - Neuroinflammation

KW - Type 2 diabetes

KW - Zebrafish

KW - DEPRESSION

KW - POPULATION

KW - BLOOD-GLUCOSE

KW - RISK

KW - MODEL

KW - ADULT ZEBRAFISH

KW - HYPERGLYCEMIA

KW - NEUROSCIENCE RESEARCH

KW - TNF-ALPHA

KW - STRESS

UR - http://www.scopus.com/inward/record.url?scp=85071846204&partnerID=8YFLogxK

U2 - 10.1016/j.pnpbp.2019.109752

DO - 10.1016/j.pnpbp.2019.109752

M3 - Article

C2 - 31446160

VL - 96

JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry

SN - 0278-5846

M1 - 109752

ER -