Ting-Ting Liu1, Xiao-Lian Ye2, Jin-Ping Zhang2,3, Ting-Ting Yu4, Shan-Shan Cheng1, Xiao-Chuan Zou1, Yun Xu5, Gui-Quan Chen1, Zhen-Yu Yin4. 1. State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Jiangsu Provincial Key Medical Discipline, Nanjing University, Nanjing, China. 2. Department of Pharmacy, China Pharmaceutical University, Nanjing, China. 3. Department of Medicament, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. 4. Department of Geriatric, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. 5. Department of Neurology, Jiangsu Provincial Key Medical Discipline, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
Abstract
AIMS: This study was to investigate whether cell proliferation and adult neurogenesis are affected at early neurodegenerative stage when neuron loss has not begun to display. METHODS AND RESULTS: Forebrain-specific nicastrin (NCT) conditional knockout (cKO) mice were generated by crossing NCTf/f with CaMKIIα-Cre Tg mice. BrdU was used as a lineage tracer to label proliferating neural progenitor cells (NPCs). Immunohistochemistry (IHC) on BrdU indicated that the total number of BrdU positive (+) cells was increased in NCT cKO mice. IHC on doublecortin (DCX) showed that the total number of DCX+ cells was also increased in NCT cKO mice. NCT cKO mice displayed significant astrogliosis as well. However, NCT cKO mice at 3 months did not show significant neuronal death or synaptic loss. CONCLUSIONS: NCT-dependent γ-secretase activity plays an important role in cell proliferation and immature neuron generation. Enhanced neurogenesis and astrogliosis may be early cellular events prior to the occurrence of neuronal death in neurodegenerative disease.
AIMS: This study was to investigate whether cell proliferation and adult neurogenesis are affected at early neurodegenerative stage when neuron loss has not begun to display. METHODS AND RESULTS: Forebrain-specific nicastrin (NCT) conditional knockout (cKO) mice were generated by crossing NCTf/f with CaMKIIα-Cre Tg mice. BrdU was used as a lineage tracer to label proliferating neural progenitor cells (NPCs). Immunohistochemistry (IHC) on BrdU indicated that the total number of BrdU positive (+) cells was increased in NCT cKO mice. IHC on doublecortin (DCX) showed that the total number of DCX+ cells was also increased in NCT cKO mice. NCT cKO mice displayed significant astrogliosis as well. However, NCT cKO mice at 3 months did not show significant neuronal death or synaptic loss. CONCLUSIONS: NCT-dependent γ-secretase activity plays an important role in cell proliferation and immature neuron generation. Enhanced neurogenesis and astrogliosis may be early cellular events prior to the occurrence of neuronal death in neurodegenerative disease.
Authors: Laura K Hamilton; Anne Aumont; Carl Julien; Alexandra Vadnais; Frédéric Calon; Karl J L Fernandes Journal: Eur J Neurosci Date: 2010-08-19 Impact factor: 3.386
Authors: Dan Xia; Hirotaka Watanabe; Bei Wu; Sang Hun Lee; Yan Li; Evgeny Tsvetkov; Vadim Y Bolshakov; Jie Shen; Raymond J Kelleher Journal: Neuron Date: 2015-03-04 Impact factor: 17.173