Methionine-Choline Deprivation Impairs Adult Hippocampal Neurogenesis in C57BL/6 Mice

Kim, Jong Whi; Hahn, Kyu Ri; Yoo, Dae Young; Jung, Hyo Young; Hwang, In Koo; Seong, Je Kyung; Yoon, Yeo Sung

doi:10.1089/jmf.2018.4247

Cited by 9 publications

(6 citation statements)

References 54 publications

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“…Choline is a source of acetylcholine (essential in neuronal signaling), phosphocholine, phosphatidylcholine and sphingomyelin, all important components of the cell membrane [15,16]. It was not surprising that the deprivation of methionine and choline can cause a decrease in survival of neural stem cells (NSCs) and transformation into mature neurons in C57BL/6 mice [17]. This can be problematic, as several groups are investigating cortical influences of systemic pathologies.…”

Section: Introductionmentioning

confidence: 99%

Cerebrolysin Use in Patients with Liver Damage—A Translational Study

Morega

Gresita

Mitran

et al. 2022

Life

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The treatment of acute life-threatening events in patients suffering from chronic pathologies is problematic, as physicians need to consider multisystemic drug effects. Regarding Cerebrolysin, a Sonic Hedgehog signaling pathway amplifier and one of the few approved neurotrophic treatments for stroke patients, concerns of excessive Hedgehog pathway activation that could accelerate NAFLD progression to cirrhosis seem valid. We investigated stroke patients treated with Cerebrolysin that presented elevated levels of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT). We also investigated the efficiency of Cerebrolysin in reversing the neurogenesis inhibition within the hippocampus in a mouse model of NAFLD by evaluating behavior and histological outcomes. NeuN, BrdU and Iba1 positive signals in the cortex and hippocampus of the animals were also observed. Clinically, Cerebrolysin improved AST levels in a majority of stroke patients with hepatic damage. The same treatment in an experimental setup was able to reverse anxiety-like behavior in MCD mice, reducing their freezing time from 333.61 ± 21.81 s in MCD animals to 229.17 ± 26.28 in treated ones. The use of Cerebrolysin did not improve short-term memory nor rescued cell multiplication in the hippocampus after MCD food intake. Understanding the neuroprotective and neurotrophic effects that drugs have on NAFLD patients can significantly contribute to a suitable therapeutic approach.

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Section: Introductionmentioning

confidence: 99%

Cerebrolysin Use in Patients with Liver Damage—A Translational Study

Morega

Gresita

Mitran

et al. 2022

Life

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“…However, no study to date has investigated the effects of TRF in the context of NASH induced by MCDD. Although MCDD does have its limitations and impacts other tissues, including weight loss and the absence of insulin resistance, increased lipolysis in adipose tissue, intestinal inflammation, and impaired hippocampal neurogenesis, it has been a commonly used dietary model for NASH in mice, which results in liver injury characterized by excessive fat accumulation, inflammation, and fibrosis [50][51][52][53][54][55]. In our study, we observed that TRF significantly reduced hepatic lipid accumulation and liver damage caused by the MCDD.…”

Section: Discussionmentioning

confidence: 48%

Time-Restricted Feeding Ameliorates Methionine–Choline Deficient Diet-Induced Steatohepatitis in Mice

Jung,

Ahima,

Kim

2024

IJMS

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Non-alcoholic steatohepatitis (NASH) is an inflammatory form of non-alcoholic fatty liver disease (NAFLD), closely associated with disease progression, cirrhosis, liver failure, and hepatocellular carcinoma. Time-restricted feeding (TRF) has been shown to decrease body weight and adiposity and improve metabolic outcomes; however, the effect of TRF on NASH has not yet been fully understood. We had previously reported that inositol polyphosphate multikinase (IPMK) mediates hepatic insulin signaling. Importantly, we have found that TRF increases hepatic IPMK levels. Therefore, we investigated whether there is a causal link between TRF and IPMK in a mouse model of NASH, i.e., methionine- and choline-deficient diet (MCDD)-induced steatohepatitis. Here, we show that TRF alleviated markers of NASH, i.e., reduced hepatic steatosis, liver triglycerides (TG), serum alanine transaminase (ALT) and aspartate aminotransferase (AST), inflammation, and fibrosis in MCDD mice. Interestingly, MCDD led to a significant reduction in IPMK levels, and the deletion of hepatic IPMK exacerbates the NASH phenotype induced by MCDD, accompanied by increased gene expression of pro-inflammatory chemokines. Conversely, TRF restored IPMK levels and significantly reduced gene expression of proinflammatory cytokines and chemokines. Our results demonstrate that TRF attenuates MCDD-induced NASH via IPMK-mediated changes in hepatic steatosis and inflammation.

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“…There are several reports regarding the relationship between choline and neural development. Researchers reported that a choline-deficient diet suppressed NSC proliferation and differentiation in the mouse hippocampus [32]. Therefore, it is crucial to understand the role and dynamics of choline as well as the molecular and cellular consequences of choline deficiency in hNSCs.…”

Section: Discussionmentioning

confidence: 99%

Functional Expression of Choline Transporters in Human Neural Stem Cells and Its Link to Cell Proliferation, Cell Viability, and Neurite Outgrowth

Fujita¹,

Nagakura²,

Uchino³

et al. 2021

Preprint

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Choline and choline metabolites are essential for all cellular functions. They have also been reported to be crucial for neural development. In this work, we studied the functional characteristics of the choline uptake system in human neural stem cells (hNSCs). Additionally, we investigated the effect of extracellular choline uptake inhibition on the cellular activities in hNSCs. We found that the mRNAs and proteins of choline transporter-like protein 1 (CTL1) and CTL2 were expressed at high levels. Immunostaining showed that CTL1 and CTL2 were localized in the cell membrane and partly in the mitochondria, respectively. The uptake of extracellular choline was saturable and performed by a single uptake mechanism, which was Na+-independent and pH-dependent. We conclude that CTL1 is responsible for extracellular choline uptake, and CTL2 may uptake choline in the mitochondria and be involved in DNA methylation via choline oxidation. Extracellular choline uptake inhibition caused intracellular choline deficiency in hNSCs, which suppressed cell proliferation, cell viability, and neurite outgrowth. Our findings contribute to the understanding of the role of choline in neural development as well as the pathogenesis of various neurological diseases caused by choline deficiency or choline uptake impairment.

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Methionine-Choline Deprivation Impairs Adult Hippocampal Neurogenesis in C57BL/6 Mice

Cited by 9 publications

References 54 publications

Cerebrolysin Use in Patients with Liver Damage—A Translational Study

Cerebrolysin Use in Patients with Liver Damage—A Translational Study

Time-Restricted Feeding Ameliorates Methionine–Choline Deficient Diet-Induced Steatohepatitis in Mice

Functional Expression of Choline Transporters in Human Neural Stem Cells and Its Link to Cell Proliferation, Cell Viability, and Neurite Outgrowth

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