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NAD+ Modulates the Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells via Akt Signaling Pathway.

ABSTRACT: Nicotinamide adenine dinucleotide hydrate (NAD+) acts as the essential component of the tricarboxylic citric acid (TCA) cycle and has important functions in diverse biological processes. However, the roles of NAD+ in regulating adult neural stem/progenitor cells (aNSPCs) remain largely unknown. Here, we show that NAD+ exposure leads to the reduced proliferation and neuronal differentiation of aNSPCs and induces the apoptosis of aNSPCs. In addition, NAD+ exposure inhibits the morphological development of neurons. Mechanistically, RNA sequencing revealed that the transcriptome of aNSPCs is altered by NAD+ exposure. NAD+ exposure significantly decreases the expression of multiple genes related to ATP metabolism and the PI3k-Akt signaling pathway. Collectively, our findings provide some insights into the roles and mechanisms in which NAD+ regulates aNSPCs and neuronal development.

SUBMITTER: Huang X

PROVIDER: S-EPMC9029130 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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NAD+ Modulates the Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells via Akt Signaling Pathway.

Huang Xiaoli X Guo Hongfeng H Cheng Xuejun X Zhang Jinyu J Qu Wenzheng W Ding Qianyun Q Sun Qihang Q Shu Qiang Q Li Xuekun X

Cells 20220409 8

Nicotinamide adenine dinucleotide hydrate (NAD+) acts as the essential component of the tricarboxylic citric acid (TCA) cycle and has important functions in diverse biological processes. However, the roles of NAD+ in regulating adult neural stem/progenitor cells (aNSPCs) remain largely unknown. Here, we show that NAD+ exposure leads to the reduced proliferation and neuronal differentiation of aNSPCs and induces the apoptosis of aNSPCs. In addition, NAD+ exposure inhibits the morphological develo ...[more]

PMID: 35455963

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NAD+ Modulates the Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells via Akt Signaling Pathway

Project description:Collectively, our findings provide some insights into the roles and mechanisms in which NAD+ regulates aNSPCs and neuronal development.

2022-04-27 | GSE200494 | GEO

NAD+ Modulates the Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells via Akt Signaling Pathway

Project description:NAD+ Modulates the Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells via Akt Signaling Pathway

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miR?29 promotes the proliferation of cultured rat neural stem/progenitor cells via the PTEN/AKT signaling pathway.

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Project description:Contactin-associated protein 4 (Caspr4), also known as contactin-associated protein-like protein (CNTNAP4), is expressed in various regions of the brain. Recent reports suggest that CNTNAP4 is a susceptibility gene of autism spectrum disorders (ASDs). However, the molecular function of Caspr4 in the brain has yet to be identified. In this study, we show an essential role of Caspr4 in neural progenitor cells (NPCs). Caspr4 is expressed in NPCs in the subventricular zone (SVZ), a neurogenic region in the developing cortex. Knocking down of Caspr4 enhances the proliferation of NPCs derived from the SVZ of embryonic day 14 mouse. Neuronal differentiation is increased by overexpression of Caspr4, but decreased by knocking down of Caspr4 in cultured mouse NPCs. Transfection of the intracellular domain of Caspr4 (C4ICD) rescues the abnormal decreased neuronal differentiation of Caspr4-knocking down NPCs. Ligand of Numb protein X2 (LNX2), a binding partner of Numb, interacts with Caspr4 in a PDZ domain-dependent manner and plays a similar role to Caspr4 in NPCs. Moreover, transfection of LNX2 rescues the decreased neuronal differentiation in Caspr4-knocking down NPCs. In contrast, transfection of C4ICD fails to do so in LNX2-knocking down NPCs. These results indicate that Caspr4 inhibits neuronal differentiation in a LNX-dependent manner. Therefore, this study reveals a novel role of Caspr4 through LNX2 in NPCs, which may link to the pathogenesis of ASDs.

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Cell type-dependent Erk-Akt pathway crosstalk regulates the proliferation of fetal neural progenitor cells.

Project description:Neural progenitor (NP) cells are the multipotent cells that produce neurons and glia in the central nervous system. Compounds regulating their proliferation are key to both understanding brain development and unlocking their potential in regenerative repair. We discuss a chemical screen that unexpectedly identified inhibitors of Erk signaling potently promoting the self-renewing divisions of fetal NP cells. This occurred through crosstalk between Erk and Akt signaling cascades. The crosstalk mechanism is cell type-specific, and is not detected in adult NP cells as well as brain tumor cells. The mechanism was also shown to be independent from the GSK-3 signaling pathway, which has been reported to be a major regulator of NP cell homeostasis and inhibitors to which were also identified in the screen. In vitro Erk inhibition led to the prolonged rapid expansion of fetal NP cells while retaining their multipotency. In vivo inhibitor administration significantly inhibited the neuronal differentiation, and resulted in increased proliferative progenitor cells in the ventricular/subventricular zone (VZ/SVZ) of the embryonic cortex. Our results uncovered a novel regulating pathway for NP cell proliferation in the developing brain. The discovery provides a pharmacological basis for in vitro expansion and in vivo manipulation of NP cells.

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Mitochondrial Complex I Function Is Essential for Neural Stem/Progenitor Cells Proliferation and Differentiation.

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Project description:BackgroundNeural stem cells (NSCs) are undifferentiated precursor cells that have the ability to self-renew and proliferate and have the capacity to become either glia (oligodendrocytes and astrocytes) or neurons. NSCs can act as beneficial adjuncts for many neurological disorders, such as cerebral infarction, spinal cord injuries, Alzheimer's disease, and Parkinson's disease. Long noncoding RNAs (lncRNAs) play essential roles during cell differentiation, proliferation, and metabolism. This study aimed to explore the role played by adipocyte differentiation-associated long noncoding RNA (ADNCR) in the self-renewal and multipotency of NSCs.MethodsIn this study, we identified NSCs and verified that these cells were able to regenerate and differentiate into both astrocytes and neurons. Then we studied the relation between expression of ADNCR and transcription factor 3 (TCF3) and proliferation of NSCs.ResultsADNCR and TCF3 expression have been shown to decrease during the differentiation of NSCs into both neurons and astrocyte induction cells. However, the expression of the microRNA miR-204-5p increased over time during the differentiation of NSCs into both neurons and astrocyte induction cells. ADNCR acts as a competing endogenous RNA (ceRNA) for miR-204-5p, and the overexpression of ADNCR suppressed miR-204-5p expression and enhanced TCF3 expression in NSCs, which resulted in enhanced proliferation and suppressed neural differentiation.ConclusionsThese data suggested that the use of ADNCR may represent a new strategy for expanding the interventions used to treat neurological disorders.

| S-EPMC7475390 | biostudies-literature

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