Dataset Information

NOX4 Deficiency Exacerbates the Impairment of Cystatin C-Dependent Hippocampal Neurogenesis by a Chronic High Fat Diet.

ABSTRACT: Hippocampal neurogenesis is linked with a cognitive process under a normal physiological condition including learning, memory, pattern separation, and cognitive flexibility. Hippocampal neurogenesis is altered by multiple factors such as the systemic metabolic changes. NADPH oxidase 4 (NOX4) has been implicated in the regulation of brain function. While the role of NOX4 plays in the brain, the mechanism by which NOX4 regulates hippocampal neurogenesis under metabolic stress is unclear. In this case, we show that NOX4 deficiency exacerbates the impairment of hippocampal neurogenesis by inhibiting neuronal maturation by a chronic high fat diet (HFD). NOX4 deficiency resulted in less hippocampal neurogenesis by decreasing doublecortin (DCX)-positive neuroblasts, a neuronal differentiation marker, and their branched-dendrites. Notably, NOX4 deficiency exacerbates the impairment of hippocampal neurogenesis by chronic HFD. Moreover, NOX4 deficiency had a significant reduction of Cystatin C levels, which is critical for hippocampal neurogenesis, under chronic HFD as well as normal chow (NC) diet. Furthermore, the reduction of Cystatin C levels was correlated with the impairment of hippocampal neurogenesis in NOX4 deficient and wild-type (WT) mice under chronic HFD. Our results suggest that NOX4 regulates the impairment of Cystatin C-dependent hippocampal neurogenesis under chronic HFD.

SUBMITTER: Jiranugrom P

PROVIDER: S-EPMC7291165 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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NOX4 Deficiency Exacerbates the Impairment of Cystatin C-Dependent Hippocampal Neurogenesis by a Chronic High Fat Diet.

Jiranugrom Piyanart P Yoo Ik Dong ID Park Min Woo MW Ryu Ji Hwan JH Moon Jong-Seok JS Yi Sun Shin SS

Genes 20200519 5

Hippocampal neurogenesis is linked with a cognitive process under a normal physiological condition including learning, memory, pattern separation, and cognitive flexibility. Hippocampal neurogenesis is altered by multiple factors such as the systemic metabolic changes. NADPH oxidase 4 (NOX4) has been implicated in the regulation of brain function. While the role of NOX4 plays in the brain, the mechanism by which NOX4 regulates hippocampal neurogenesis under metabolic stress is unclear. In this c ...[more]

PMID: 32438638

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Project description:Radiation-induced impairment of neurogenesis in the hippocampal dentate gyrus is a concern due to its reported association with cognitive detriments after radiotherapy for brain cancers and the possible risks to astronauts chronically exposed to space radiation. Here, we have extended our recent work in a mouse model of impaired neurogenesis after exposure to low-linear energy transfer (LET) radiation to heavy ion irradiation. To our knowledge, this is the first report of a predictive mathematical model of radiation-induced changes to neurogenesis for a variety of radiation types after acute or fractionated irradiation. We used a system of nonlinear ordinary differential equations (ODEs) to represent age, time after exposure and dose-dependent changes to several cell populations participating in neurogenesis, as reported in mouse experiments. We considered four compartments to model hippocampal neurogenesis and, consequently, the effects of radiation in altering neurogenesis: 1. neural stem cells (NSCs); 2. neuronal progenitor cells or neuroblasts (NB); 3. immature neurons (ImN); and 4. glioblasts (GB), with additional consideration of microglial activation. The model describes the negative feedback regulation on early and late neuronal proliferation after irradiation, and the dynamics of the age dependence of neurogenesis. We compared our model to experimental data for X rays, and protons, carbon and iron particles, including data for fractionated iron-particle irradiation. Heavy-ion irradiation is predicted to lead to poor recovery or no recovery from impaired neurogenesis at doses as low as 0.5 Gy in mice. This is only partially ameliorated by dose fractionation, which suggests important implications for Hardon therapy near the Bragg peak, and possibly for space radiation exposures as well. Predictions of the threshold doses where neurogenesis recovery fails for given radiation types are described, and the role of subthreshold transient impairments are briefly discussed.

Dataset Information

NOX4 Deficiency Exacerbates the Impairment of Cystatin C-Dependent Hippocampal Neurogenesis by a Chronic High Fat Diet.

Publications

NOX4 Deficiency Exacerbates the Impairment of Cystatin C-Dependent Hippocampal Neurogenesis by a Chronic High Fat Diet.

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