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The present study investigated the influence of seipin deficiency on adult neurogenesis in hippocampal dentate gyrus (DG) and the underlying mechanisms. Here, we show that the proliferative capability of stem cells in seipin-nKO mice was significantly reduced compared to WT mice, which could be rescued by the PPAR\u03b3 agonist rosiglitazone (rosi). In seipin-nKO mice, the neuronal differentiation of progenitor cells was inhibited with the enhancement of astrogliogenesis, which were recovered by the rosi-treatment during early stages of progenitor cells differentiation. In addition, the rosi-treatment could correct the decline in hippocampal ERK2 phosphorylation and cyclin A mRNA level in seipin-nKO mice. The MEK inhibitor U0126 abolished the rosi-rescued cell proliferation and cyclin A expression in seipin-nKO mice. In seipin-nKO mice, the hippocampal Wnt3 protein level was less than that in WT mice with the reduction of Neurog1 and NeuroD1 mRNA, which were corrected by the rosi-treatment. The STAT3 phosphorylation (Tyr-705) was enhanced in seipin-nKO mice, which was further elevated by the rosi-treatment. Finally, the rosi-treatment for 10 days could alleviate depression-like phenotype in seipin-nKO mice, which was blocked by the MEK inhibitor U0126. The results indicate that the seipin deficiency by reducing PPAR\u03b3 impairs proliferation and differentiation of adult neural stem\/progenitor cells in DG, which may be responsible for the production of depression-like phenotype in seipin-nKO mice.<\/jats:p>","DOI":"10.1242\/dmm.021550","type":"journal-article","created":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T01:33:19Z","timestamp":1442971999000},"source":"Crossref","is-referenced-by-count":10,"title":["Seipin knockout impairs proliferation and differentiation of adult stem\/progenitor cells in hippocampal dentate gyrus <i>via<\/i> reduction of PPAR\u03b3"],"prefix":"10.1242","author":[{"given":"Guoxi","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China"},{"name":"Department of Physiology, Nanjing Medical University, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Libin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nanjing Medical University, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nanjing Medical University, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conghui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nanjing Medical University, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sha","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nanjing Medical University, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xunde","family":"Xian","sequence":"additional","affiliation":[{"name":"Depatment of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX 75390 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Ji","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, Peking University and Key Laboratory of Cardiovascular Sciences, China Administration of Education, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China"},{"name":"Department of Physiology, Nanjing Medical University, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2021042513093011500_DMM021550C1","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/S1043-2760(03)00078-X","article-title":"Congenital generalized lipodystrophy: significance of triglyceride biosynthetic pathways","volume":"14","author":"Agarwal","year":"2003","journal-title":"Trends Endocrinol. 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