Involvement of LIN28A in Wnt-dependent regulation of hippocampal neurogenesis in the aging brain

Zhu, Chun-Ling; Ma, Jiao; Yue, Huimin; Luo, Yujian; Li, Xiaofang; Wang, Chao; Wang, Liang; Sun, Binggui; Chen, Zhong; Wang, Lang; Gu, Yan

doi:10.1016/j.stemcr.2022.05.016

Cited by 2 publications

(1 citation statement)

References 44 publications

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“…Moreover, GSK-3 also functions as an age-related factor in the brain, whose activation accelerates the decline of adult hippocampal neurogenesis (Liu, Tian, et al, 2020). Interestingly, the RNA-binding protein LIN28A modulates adult neurogenesis through an intracellular mechanism in response to Wnt signaling from the SGZ niche, and its decline is associated with age-related impairment of neurogenesis and cognitive functions (Hu et al, 2022).…”

Section: Agingmentioning

confidence: 99%

Adult neurogenesis research in China

Luo,

Xu,

Guo

2023

Dev Growth Differ

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Neural stem cells are multipotent stem cells that generate functional newborn neurons through a process called neurogenesis. Neurogenesis in the adult brain is tightly regulated and plays a pivotal role in the maintenance of brain function. Disruption of adult neurogenesis impairs cognitive function and is correlated with numerous neurologic disorders. Deciphering the mechanisms underlying adult neurogenesis not only advances our understanding of how the brain functions, but also offers new insight into neurologic diseases and potentially contributes to the development of effective treatments. The field of adult neurogenesis is experiencing significant growth in China. Chinese researchers have demonstrated a multitude of factors governing adult neurogenesis and revealed the underlying mechanisms of and correlations between adult neurogenesis and neurologic disorders. Here, we provide an overview of recent advancements in the field of adult neurogenesis due to Chinese scientists.

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Section: Agingmentioning

confidence: 99%

Adult neurogenesis research in China

Luo,

Xu,

Guo

2023

Dev Growth Differ

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GRM2 Regulates Functional Integration of Adult-Born DGCs by Paradoxically Modulating MEK/ERK1/2 Pathway

Zhu

Yue

et al. 2023

J. Neurosci.

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Metabotropic glutamate receptor 2 (GRM2) is highly expressed in hippocampal dentate granule cells (DGCs), regulating synaptic transmission and hippocampal functions. Newborn DGCs are continuously generated throughout life, and express GRM2 when they are mature. However, it remained unclear whether and how GRM2 regulates the development and integration of these newborn neurons. We discovered that the expression of GRM2 in adult-born DGCs increased with neuronal development in mice of both sexes. Lack of GRM2 caused developmental defects of DGCs and impaired hippocampus-dependent cognitive functions. Intriguingly, our data showed that knockdown ofGrm2resulted in decreased b/c-Raf kinases, and paradoxically led to an excessive activation of MEK/ERK1/2 pathway. Inhibition of MEK ameliorated the developmental defects caused byGrm2knockdown. Together, our results indicate that GRM2 is necessary for the development and functional integration of newborn DGCs in the adult hippocampus through regulating the phosphorylation and activation state of MEK/ERK1/2 pathway.SIGNIFICANCE STATEMENT:Metabotropic glutamate receptor 2 (GRM2) is highly expressed in mature dentate granule cells (DGCs) in the hippocampus. It remains unclear whether GRM2 is required for the development and integration of adult-born DGCs. We provided a series ofin vivoandin vitroevidence to show GRM2 regulates the development of adult-born DGCs and their integration into existing hippocampal circuits. Lack of GRM2 in a cohort of newborn DGCs impaired object-to-location memory in mice. Moreover, we revealed that GRM2 knockdown paradoxically upregulated MEK/ERK1/2 pathway by suppressing b/c-Raf in developing neurons, which is likely a common mechanism underlying the regulation of the development of neurons expressing GRM2. Thus, Raf/MEK/ERK1/2 pathway could be a potential target for brain diseases related to GRM2 abnormality.

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Involvement of LIN28A in Wnt-dependent regulation of hippocampal neurogenesis in the aging brain

Cited by 2 publications

References 44 publications

Adult neurogenesis research in China

Adult neurogenesis research in China

GRM2 Regulates Functional Integration of Adult-Born DGCs by Paradoxically Modulating MEK/ERK1/2 Pathway

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