<scp>MiR</scp>‐181a‐5p promotes neural stem cell proliferation and enhances the learning and memory of aged mice

Sun, Qiaoyi; Ma, Li; Qiao, Jing; Wang, Xing; Li, Jianguo; Wang, Yuxi; Tan, Ailing; Ye, Zihui; Wu, Yukang; Xi, Jiajie; Kang, Jiuhong

doi:10.1111/acel.13794

Cited by 4 publications

(2 citation statements)

References 56 publications

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“…In this study, our findings suggested that CCN3 regulated the activation of the Notch/PTEN/AKT signaling pathway, thereby influencing the proliferation and neuronal differentiation of NSCs. The Notch/PTEN/AKT signaling pathway is closely related to the proliferation and differentiation of NSCs [ 36 , 37 , 38 ]. However, the effects of CCN3 cannot be solely explained by the promotion of Notch/PTEN/AKT signaling pathway activation.…”

Section: Discussionmentioning

confidence: 99%

CCN3/NOV Regulates Proliferation and Neuronal Differentiation in Mouse Hippocampal Neural Stem Cells via the Activation of the Notch/PTEN/AKT Pathway

Luan

Zhang

et al. 2023

IJMS

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Neural stem cells (NSCs) persist in the subgranular zone (SGZ) throughout the lifespan and hold immense potential for the repair and regeneration of the central nervous system, including hippocampal-related diseases. Several studies have demonstrated that cellular communication network protein 3 (CCN3) regulates multiple types of stem cells. However, the role of CCN3 in NSCs remains unknown. In this study, we identified CCN3 expression in mouse hippocampal NSCs and observed that supplementing CCN3 improved cell viability in a concentration-dependent manner. Additionally, in vivo results showed that the injection of CCN3 in the dentate gyrus (DG) increased Ki-67- and SOX2-positive cells while decreasing neuron-specific class III beta-tubulin (Tuj1) and doublecortin (DCX)-positive cells. Consistently with the in vivo results, supplementing CCN3 in the medium increased the number of BrdU and Ki-67 cells and the proliferation index but decreased the number of Tuj1 and DCX cells. Conversely, both the in vivo and in vitro knockdown of the Ccn3 gene in NSCs had opposite effects. Further investigations revealed that CCN3 promoted cleaved Notch1 (NICD) expression, leading to the suppression of PTEN expression and eventual promotion of AKT activation. In contrast, Ccn3 knockdown inhibited the activation of the Notch/PTEN/AKT pathway. Finally, the effects of changes in CCN3 protein expression on NSC proliferation and differentiation were eliminated by FLI-06 (a Notch inhibitor) and VO-OH (a PTEN inhibitor). Our findings imply that while promoting proliferation, CCN3 inhibits the neuronal differentiation of mouse hippocampal NSCs and that the Notch/PTEN/AKT pathway may be a potential intracellular target of CCN3. Our findings may help develop strategies to enhance the intrinsic potential for brain regeneration after injuries, particularly stem cell treatment for hippocampal-related diseases.

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Section: Discussionmentioning

confidence: 99%

CCN3/NOV Regulates Proliferation and Neuronal Differentiation in Mouse Hippocampal Neural Stem Cells via the Activation of the Notch/PTEN/AKT Pathway

Luan

Zhang

et al. 2023

IJMS

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“…With age, reduced miR-181a levels impair T-cell functions ( 43 , 44 ). MiR-181a-5p was downregulated in hippocampal neural stem cells from senescent mice and was involved in hippocampal-dependent learning and memory deficits associated with aging ( 45 ). Therefore, miRNAs mediate the onset of aging, and their roles and characteristics in a variety of age-related diseases hold great promise as critical indicators for early diagnosis and treatment of age-related diseases.…”

Section: Senescence and Agingmentioning

confidence: 99%

Cellular senescence in skeletal disease: mechanisms and treatment

He,

Hu,

Zhang

et al. 2023

Cell Mol Biol Lett

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The musculoskeletal system supports the movement of the entire body and provides blood production while acting as an endocrine organ. With aging, the balance of bone homeostasis is disrupted, leading to bone loss and degenerative diseases, such as osteoporosis, osteoarthritis, and intervertebral disc degeneration. Skeletal diseases have a profound impact on the motor and cognitive abilities of the elderly, thus creating a major challenge for both global health and the economy. Cellular senescence is caused by various genotoxic stressors and results in permanent cell cycle arrest, which is considered to be the underlying mechanism of aging. During aging, senescent cells (SnCs) tend to aggregate in the bone and trigger chronic inflammation by releasing senescence-associated secretory phenotypic factors. Multiple signalling pathways are involved in regulating cellular senescence in bone and bone marrow microenvironments. Targeted SnCs alleviate age-related degenerative diseases. However, the association between senescence and age-related diseases remains unclear. This review summarises the fundamental role of senescence in age-related skeletal diseases, highlights the signalling pathways that mediate senescence, and discusses potential therapeutic strategies for targeting SnCs. Graphical Abstract

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Bioinformatics Analysis of miR-181a and Its Role in Adipogenesis, Obesity, and Lipid Metabolism Through Review of Literature

Hongfang,

Khan,

El-Mansi

2023

Mol Biotechnol

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MiR‐181a‐5p promotes neural stem cell proliferation and enhances the learning and memory of aged mice

Cited by 4 publications

References 56 publications

CCN3/NOV Regulates Proliferation and Neuronal Differentiation in Mouse Hippocampal Neural Stem Cells via the Activation of the Notch/PTEN/AKT Pathway

CCN3/NOV Regulates Proliferation and Neuronal Differentiation in Mouse Hippocampal Neural Stem Cells via the Activation of the Notch/PTEN/AKT Pathway

Cellular senescence in skeletal disease: mechanisms and treatment

Bioinformatics Analysis of miR-181a and Its Role in Adipogenesis, Obesity, and Lipid Metabolism Through Review of Literature

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