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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Characterization of age- and stage-dependent impaired adult subventricular neurogenesis in 5XFAD mouse model of Alzheimer's disease

  • Hyun Ha Park (Department of Biochemistry, College of Medicine, Konyang University) ;
  • Byeong-Hyeon Kim (Department of Biochemistry, College of Medicine, Konyang University) ;
  • Seol Hwa Leem (Department of Biochemistry, College of Medicine, Konyang University) ;
  • Yong Ho Park (Department of Biochemistry, College of Medicine, Konyang University) ;
  • Hyang-Sook Hoe (Department of Neural Development and Disease, Korea Brain Research Institute (KBRI)) ;
  • Yunkwon Nam (Department of Biochemistry, College of Medicine, Konyang University) ;
  • Sujin Kim (Department of Biochemistry, College of Medicine, Konyang University) ;
  • Soo Jung Shin (Department of Biochemistry, College of Medicine, Konyang University) ;
  • Minho Moon (Department of Biochemistry, College of Medicine, Konyang University)
  • Received : 2023.05.02
  • Accepted : 2023.07.05
  • Published : 2023.09.30
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Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline. Several recent studies demonstrated that impaired adult neurogenesis could contribute to AD-related cognitive impairment. Adult subventricular zone (SVZ) neurogenesis, which occurs in the lateral ventricles, plays a crucial role in structural plasticity and neural circuit maintenance. Alterations in adult SVZ neurogenesis are early events in AD, and impaired adult neurogenesis is influenced by the accumulation of intracellular Aβ. Although Aβ-overexpressing transgenic 5XFAD mice are an AD animal model well representative of Aβ-related pathologies in the brain, the characterization of altered adult SVZ neurogenesis following AD progression in 5XFAD mice has not been thoroughly examined. Therefore, we validated the characterization of adult SVZ neurogenesis changes with AD progression in 2-, 4-, 8-, and 11-monthold male 5XFAD mice. We first investigated the Aβ accumulation in the SVZ using the 4G8 antibody. We observed intracellular Aβ accumulation in the SVZ of 2-month-old 5XFAD mice. In addition, 5XFAD mice exhibited significantly increased Aβ deposition in the SVZ with age. Next, we performed a histological analysis to investigate changes in various phases of adult neurogenesis, such as quiescence, proliferation, and differentiation, in SVZ. Compared to age-matched wild-type (WT) mice, quiescent neural stem cells were reduced in 5XFAD mice from 2-11 months of age. Moreover, proliferative neural stem cells were decreased in 5XFAD mice from 2 to 8 months of age. Furthermore, differentiations of neuroblasts were diminished in 5XFAD mice from 2-11 months of age. Intriguingly, we found that adult SVZ neurogenesis was reduced with aging in healthy mice. Taken together, our results revealed that impairment of adult SVZ neurogenesis appears with aging or AD progression.

Keywords

Acknowledgement

This work was supported by Basic Science Research Program of the National Research Foundation of Korea (NRF), which is funded by the Ministry of Science, ICT & Future Planning (grant number: NRF-2018R1D1A3B07041059 to M.M. and NRF-2022R1A6A3A13053190 to Y.N and RS-2023-00212388 to S.K.) and was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HF21C0021 and HI23C1263 to M.M.). This work was also supported by the Korea Brain Research Institute (KBRI) basic research program through KBRI funded by the Ministry of Science, ICT & Future Planning (grant number: 22-BR-02-03 to H-S.H.).

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