title: Effects of ADAM10 deletion on Notch-1 signaling pathway and neuronal maintenance in adult mouse brain.
abstract: A disintegrin and metalloproteinase 10 (ADAM10) has been demonstrated to regulate embryonic brain development by initiating Notch signaling. However, it is still unclear whether ADAM10 is required to activate the Notch signaling pathway in adult brain. To investigate the physiological role of ADAM10, we generated conditional knockout (cKO) mice lacking the Adam10 gene primarily in the cortex and hippocampus. We found that conditional disruption of ADAM10 resulted in a prominent decrease in the number of proliferating neuronal progenitor cells in the subgranular zone (SGZ), and a significant increase in the number of adult-generated postmitotic neurons in the hippocampal dentate gyrus (DG) due to premature neuronal differentiation. Moreover, the mutant mice also displayed an age-dependent reduction in the number of granule neurons in the hippocampal DG. It was further showed that the activation of Notch-1 and its downstream target genes Hes1, Hes5, Hey1, and Hey2 was impaired in ADAM10-deficient hippocampal tissues. Finally, Adam10 cKO mice had impaired learning and memory in the Morris water-maze. Thus, we provided experimental evidence to demonstrate that ADAM10 plays an essential role in the activation of Notch-1 signaling and has a remarkable effect on neuronal maintenance in adult mouse brain.
authors.affiliation: Department of Cellular Biology and Genetics, School of Basic Medicine,Fujian Medical University, Fuzhou 350108, China; Prenatal Diagnosis Center, Quanzhou Women and Children's Hospital, Quanzhou 362000, China.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Zhuang
authors.affiliation: Department of Cellular Biology and Genetics, School of Basic Medicine,Fujian Medical University, Fuzhou 350108, China.
authors.forename: Qiulan
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Cellular Biology and Genetics, School of Basic Medicine,Fujian Medical University, Fuzhou 350108, China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Cellular Biology and Genetics, School of Basic Medicine,Fujian Medical University, Fuzhou 350108, China. Electronic address: zhouchangwen624@sina.com.
authors.forename: Changwen
authors.initials: C
authors.lastname: Zhou
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000502:physiology*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D065853:Spatial Learning
chemical_list: D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse
keywords: ADAM10; Conditional knockout; Hippocampal dentate gyrus; Neuronal maintenance; Notch-1 signaling