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.

中文翻译：

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NOX4 缺乏加剧了慢性高脂肪饮食对胱抑素 C 依赖性海马神经发生的损害

海马神经发生与正常生理条件下的认知过程有关，包括学习、记忆、模式分离和认知灵活性。海马神经发生受到多种因素的影响，例如全身代谢变化。NADPH 氧化酶 4 (NOX4) 与大脑功能的调节有关。虽然 NOX4 在大脑中发挥作用，但 NOX4 在代谢压力下调节海马神经发生的机制尚不清楚。在这种情况下，我们表明 NOX4 缺乏通过抑制慢性高脂肪饮食 (HFD) 的神经元成熟来加剧海马神经发生的损害。NOX4 缺乏通过减少双皮质素 (DCX) 阳性神经母细胞、神经元分化标志物及其分支树突导致海马神经发生减少。尤其，NOX4 缺乏加剧了慢性 HFD 对海马神经发生的损害。此外，在慢性 HFD 和正常食物 (NC) 饮食下，NOX4 缺乏显着降低胱抑素 C 水平，这对海马神经发生至关重要。此外，胱抑素 C 水平的降低与 NOX4 缺陷和野生型 (WT) 小鼠在慢性 HFD 下海马神经发生的损伤相关。我们的结果表明，NOX4 调节慢性 HFD 下胱抑素 C 依赖性海马神经发生的损伤。胱抑素 C 水平的降低与慢性 HFD 下 NOX4 缺陷型和野生型 (WT) 小鼠海马神经发生受损相关。我们的结果表明，NOX4 调节慢性 HFD 下胱抑素 C 依赖性海马神经发生的损伤。Cystatin C 水平的降低与 NOX4 缺陷和野生型 (WT) 小鼠在慢性 HFD 下海马神经发生的损伤相关。我们的结果表明，NOX4 调节慢性 HFD 下胱抑素 C 依赖性海马神经发生的损伤。