Liu Guanghui/Wang Si/Qu Jing's research group collaborated to reveal the molecular mechanism of primate hippocampus aging

The hippocampus, as an important part of the brain, plays a vital role in learning and memory.

With age, hippocampal function gradually deteriorates, leading to the decline of cognitive function and the occurrence of a variety of human neurodegenerative diseases.

Due to the complex structure of the hippocampus and the highly heterogeneous cell composition, it is difficult for traditional research techniques to accurately reveal the aging laws and molecular regulatory networks of different cell types during the aging process of the hippocampus.

In addition, due to the limitations of ethics and sample sources, it is difficult to obtain healthy human hippocampal tissues at different ages, which limits the in-depth understanding of the aging mechanism of human hippocampus to a certain extent, and further restricts the intervention of brain aging and neurodegenerative diseases The development of means.

On May 30, 2021, Liu Guanghui's research group and Qu Jing's research group from the Institute of Zoology, Chinese Academy of Sciences collaborated with Wang Si's research group at Xuanwu Hospital of Capital Medical University and published an online publication titled "Single-nucleus transcriptomic landscape of primate hippocampal" in Protein & Cell magazine.
aging" research paper.

This study is the first to systematically map the single-cell transcriptome map of primate hippocampal aging, revealing the molecular mechanism of hippocampal dysfunction associated with aging, and exploring early warning signs and potential intervention targets for hippocampal aging and related degenerative diseases Provide an important basis.

 In this study, the researchers obtained hippocampal tissues of young and old cynomolgus monkeys.
Histological analysis found that the hippocampus tissue of old cynomolgus monkeys showed increased genomic and epigenome instability (including DNA damage).
Increased response and loss of heterochromatin), as well as a series of tissue aging-related features such as protein homeostasis imbalance and increased inflammation.

In order to further clarify the cellular and molecular changes in the aging process of primate hippocampus, the researchers used high-precision mononuclear transcriptome sequencing technology to comprehensively and systematically reveal the neural stem cells, transient amplified progenitor cells (TAPC), and immature neurons.
, Excitatory/inhibitory neurons, oligodendrocytes, microglia, and other 12 types of hippocampal gene expression characteristics.

The analysis shows that transiently amplified progenitor cells and microglia are most affected by aging, manifested as having more aging-related differentially expressed genes and enriching more high-risk genes for neurodegenerative diseases.

By drawing pseudo-time curves of neurogenesis trajectories and gene expression dynamics analysis, the researchers found that neurogenesis in the aged hippocampus tissue is mainly reflected in the decline in the proliferation of transiently expanded progenitor cells in the early stage and the impairment of neuronal function in the late stage.

In addition, through the analysis of the cells that make up the microenvironment of the old hippocampus, it was found that the pro-inflammatory response in the subpopulations of old microglia and oligodendrocytes increased, which promoted the formation of the neuroinflammatory microenvironment, which may be exacerbated.
The neurogenesis in the old hippocampus tissue is impaired, and may further lead to the decline of cognitive function and the occurrence of neurodegenerative diseases.

Figure.
The cellular and molecular basis of primate hippocampus aging.
This research reported the first high-precision mononuclear transcriptome map of primate hippocampal aging in the world, and systematically analyzed the aging of multiple cell types in primate hippocampus tissue The law of change reveals the main molecular characteristics of hippocampus aging, including changes in cell internal factors and external microenvironmental factors that are damaged by neurogenesis.

The research has deepened people's understanding of the age-related changes in hippocampal structure and function, clarified the key susceptible cell types and susceptible molecules in the aging process of the hippocampus, and provided potential for assessing the aging degree of the primate hippocampus and early warning of neurodegenerative diseases.
Diagnosing biomarkers and laying an important theoretical foundation for the development of new strategies for targeted intervention of brain aging and related neurodegenerative diseases.

Relevant data has been uploaded to Aging Atlas (https://bigd.
big.
ac.
cn/aging/index).

It is reported that Zhang Hui, a doctoral student at the Institute of Zoology, Chinese Academy of Sciences, Li Jiaming, a master student at the Beijing Institute of Genomics, Chinese Academy of Sciences, and Ren Jie, a researcher at the Beijing Institute of Genomics, Chinese Academy of Sciences, are the co-first authors.

Researcher Liu Guanghui from the Institute of Zoology, Chinese Academy of Sciences, researcher Wang Si from Xuanwu Hospital of Capital Medical University, and researcher Qu Jing from the Institute of Zoology, Chinese Academy of Sciences are the co-corresponding authors.

Original link: https://link.
springer.
com/article/10.
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