Chronic intermittent hypoxia exacerbates depressive-like behaviors in high fat diet-fed mice

This journal issue contains abstracts of the meetingSession - Chaired Posters: no. CP5BACKGROUND: There is a high prevalence of obstructive sleep apnea (OSA) in the obese population. Depressive symptoms are commonly manifested in obese and OSA patients as well as in animal models, but the pathophysiological mechanism remains elusive. Neuroinflammation plays an important role in major depressive disorder (MDD) with an activation of brain indoleamine 2,3, dioxygenase (IDO-1), a catabolic enzyme of tryptophan and serotonin, which depletes serotonin availability. We have shown that chronic intermittent hypoxia (CIH) manifested as episodic oxygen desaturation in severe OSA condition induces oxidative stress and inflammation in the rat hippocampus. Significant neuroinflammation was also observed in obese mice. AIMS AND HYPOTHESIS: We aim to examine whether CIH exacerbates high fat diet (HFD)-induced depressive-like behaviors. It is hypothesized that CIH aggravates HFD-induced depressive-like behaviors with an increased IDO-1 expression and activity mediated by oxidative stress and inflammation, leading to serotonin deficiency and apoptosis in the mice hippocampus. METHODS: Adult male C57BL/6N mice (4-week old after weaning) were either fed with HFD (45% fat) or regular diet for 13 weeks. The mice were treated with intermittent hypoxia (with inspired oxygen levels altering between 21-5% per min for 8 hours per day for a week, Apnea-Hyponea Index at 60) or in room air (normoxic control) starting at the 9th week for 4 weeks. Forced swimming test and sucrose preference test were employed to assess the behavioral despair and hedonic status of the mice. Hippocampi were harvested for the measurement of IDO-1 activity, oxidative stress, inflammatory and apoptotic markers assessed by Western blot and enzyme-linked Immunosorbent assay. RESULTS: The immobility time was increased in the forced swimming test and the percentage of sucrose consumption was decreased in the sucrose preference test in the HFD or hypoxic group when compared to the normoxic control; these changes were doubled in the mice co-treated with HFD and hypoxia. In addition, the level of lipid peroxidation was increased and the protein expressions of antioxidant enzymes (SOD-2, GPx-1) were decreased in the HFD or hypoxic group and these changes were significantly augmented in the co-treated mice. Moreover, inflammatory mediators (TNF-α, IL-1β and IL-6) and apoptotic markers (cleaved caspase-3, cleaved PARP-1) were increased in the HFD or hypoxic group and were significantly increased in the co-treated group. Furthermore, levels of the IDO expression and activity (ratio of KYN/TRP) were increased in the HFD or hypoxic group and were significantly elevated in the co-treated mice. CONCLUSION: CIH treatment aggravates depressive-like behaviors in HFD-fed mice with significant increased levels of oxidative stress, neuroinflammation and IDO-1 activity, which could augment the depletion of serotonin and apoptosis in the hippocampus

Characterization of sry-related hmg box group f genes in zebrafish hematopoiesis

Objective: The roles of Sry-related HMG box (Sox) genes in zebrafish hematopoiesis are not clearly defined. In this study, we have characterized the sequence homology, gene expression, hematopoietic functions, and regulation of sox genes in F group (SoxF) in zebrafish embryos. Materials and Methods: Expression of zebrafish SoxF genes were analyzed by whole-mount in situ hybridization, reverse transcription polymerase chain reaction, and real-time reverse transcription polymerase chain reaction of erythroid cells obtained from Tg(gata1:GFP) embryos by fluorescence-activated cell sorting. Roles of SoxF genes were analyzed in zebrafish embryos using morpholino knockdown and analyzed by whole-mount in situ hybridization and real-time reverse transcription polymerase chain reaction. Embryo patterning and vascular development were analyzed. Results: All members, except sox17, contained a putative β-catenin binding site. sox7 and 18 expressed primarily in the vasculature. sox17 expressed in the intermediate cell mass and its knockdown significantly reduced primitive erythropoiesis at 18 hours post-fertilization (hpf). Definitive hematopoiesis was unaffected. Concomitant sox7 and sox18 knockdown disrupted vasculogenesis and angiogenesis, but not hematopoiesis. sox32 knockdown delayed medial migration of hematopoietic and endothelial progenitors at 18 hpf and abolished cmyb expression at the caudal hematopoietic tissue at 48 hpf. These defects could be prevented by delaying its knockdown using a caged sox32 morpholino uncaged at 10 hpf. Knockdown of SoxF genes significantly upregulated their own expression and that of sox32 also upregulated sox18 expression. Conclusions: sox17 helped to maintain primitive hematopoiesis, whereas sox7 and sox18 regulated angiogenesis and vasculogenesis. sox32 affected both vascular and hematopoietic development through its effects on medial migration of the hematopoietic and endothelial progenitors. © 2011 ISEH - Society for Hematology and Stem Cells.link_to_subscribed_fulltex

Mechanistic roles of monoamine oxidase A in the exacerbative effect of chronic intermittent hypoxia on the depressive-like behavior in the mice model of diet-induced obesity

No. OP3Conference Theme: Science and Aging: An Era of Discover

Targeting JAK/STAT pathway in acute myeloid leukemia (AML): a potential therapeutic strategy and its link to WNT pathway

Young Investigator Award - Biomedicine: abstract no. A5

Methionine aminopeptidase 2 is required for HSC initiation and proliferation

In a chemical screening, we tested the antiangiogenic effects of fumagillin derivatives and identified fumagillin as an inhibitor of definitive hematopoiesis in zebrafish embryos. Fumagillin is known to target methionine aminopeptidase II (MetAP2), an enzyme whose function in hematopoiesis is unknown. We investigated the role of MetAP2 in hematopoiesis by using zebrafish embryo and human umbilical cord blood models. Zebrafish metap2 was expressed ubiquitously during early embryogenesis and later in the somitic region, the caudal hematopoietic tissue, and pronephric duct. metap2 was inhibited by morpholino and fumagillin treatment, resulting in increased mpo expression at 18 hours postfertilization and reduced c-myb expression along the ventral wall of dorsal aorta at 36 hours postfertilization. It also disrupted intersegmental vessels in Tg-(fli1:gfp) embryos without affecting development of major axial vasculatures. Inhibition of MetAP2 in CB CD34 + cells by fumagillin had no effect on overall clonogenic activity but significantly reduced their engraftment into immunodeficient nonobese diabetes/severe combined immunodeficiency mice. metap2 knockdown in zebrafish and inhibition by fumagillin in zebrafish and human CB CD34 + cells inhibited Calmodulin Kinase II activity and induced ERK phosphorylation. This study demonstrated a hithertoundescribed role of MetAP2 in definitive hematopoiesis and a possible link to non-canonical Wnt and ERK signaling. © 2011 by The American Society of Hematology.link_to_OA_fulltex

An occupational therapy fall reduction home visit program for community-dwelling older adults in Hong Kong after an emergency department visit for a fall

202303 bckwAccepted ManuscriptSelf-fundedPublishe

Effect of sorafenib treatment in FLT3-ITD+ acute myeloid leukemia: mechanism of non-responsive and emergence of novel clones

Young Investigator Award - Biomedicine: abstract no. A5