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TESC overexpression mitigates amyloid-ß-Induced hippocampal atrophy and memory decline.
Qi, Jinbo; Suo, Xinjun; Tian, Chunxiao; Xia, Xianyou; Qin, Wen; Wang, Ping; Tang, Jie; Xu, Jiayuan; Fu, Jilian; Liu, Nana; Yu, Chunshui; Shen, Hui; Dou, Yan.
Afiliación
  • Qi J; Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China.
  • Suo X; Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China; School of Medical Technology, Tianjin Medical University, Tianjin 300070, PR China.
  • Tian C; School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin 300070, PR China.
  • Xia X; Department of Cell Biology, School of Basic Medicine and Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, PR China.
  • Qin W; Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China.
  • Wang P; School of Medical Technology, Tianjin Medical University, Tianjin 300070, PR China.
  • Tang J; Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China.
  • Xu J; Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China.
  • Fu J; Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China.
  • Liu N; Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China.
  • Yu C; Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China; School of Medical Technology, Tianjin Medical University, Tianjin 300070, PR China.
  • Shen H; Department of Cell Biology, School of Basic Medicine and Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, PR China. Electronic address: shenhui@tmu.edu.cn.
  • Dou Y; Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, PR China. Electronic address: douyan@tmu.edu.cn.
Gene ; : 148939, 2024 Sep 13.
Article en En | MEDLINE | ID: mdl-39278373
ABSTRACT
BACKGROUND AND

OBJECTIVES:

Genome-wide association studies (GWASs) have identified numerous candidate genes for human brain-imaging phenotypes; however, the biological relevance of many of these genes remains unconfirmed. This study aimed to investigate the causal relationships among tescalcin (TESC) (a GWAS-indicated gene), hippocampal volume, Alzheimer's disease (AD), and the underlying biological mechanisms.

METHODS:

Human transcriptional data were analyzed to confirm relative TESC expression in the hippocampus. In cell experiments, RNA-seq analysis was used to identify the potential biological pathways for TESC overexpression, and immunofluorescence imaging and cell viability assays were used to evaluate the effect of TESC overexpression on neuronal structure and survival. In animal experiments, the effects of TESC overexpression on hippocampal volume and cognitive function in normal mice and amyloid-ß (Aß)-induced AD mice were investigated by 9.4 T magnetic resonance imaging and behavioral tests. Underlying mechanisms were further assessed via western blotting and electrophysiological recordings.

RESULTS:

Human transcriptional data demonstrated that TESC is primarily expressed in the hippocampus and neurons. TESC overexpression enhanced the viability of HT22 cells and reduced Aß-induced cell death. In mouse models, Tesc-overexpressing mice revealed increased hippocampal volume, likely owing to enhanced cell viability and long-term potentiation (LTP), and reducing apoptotic- and oxidation-induced hippocampal damage. TESC overexpression could significantly mitigate Aß-induced hippocampal atrophy and memory impairment, potentially by reducing Aß-induced neuronal apoptosis and LTP weakening.

CONCLUSION:

This study exemplifies the translation of GWAS findings into actionable biological knowledge and suggests that upregulation of TESC may offer a promising therapeutic strategy for AD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Gene Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Gene Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos