Low and High Molecular Weight FGF-2 Have Differential Effects on Astrocyte Proliferation, but Are Both Protective Against Aβ-Induced Cytotoxicity

Frontiers in Molecular Neuroscience. 2020;12 DOI 10.3389/fnmol.2019.00328

 

Journal Homepage

Journal Title: Frontiers in Molecular Neuroscience

ISSN: 1662-5099 (Online)

Publisher: Frontiers Media S.A.

LCC Subject Category: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry

Country of publisher: Switzerland

Language of fulltext: English

Full-text formats available: PDF, HTML, ePUB, XML

 

AUTHORS


Xi Chen (Key Laboratory of Ethnomedicine for Ministry of Education, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China)

Zhaojin Li (Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States)

Yong Cheng (Key Laboratory of Ethnomedicine for Ministry of Education, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China)

Yong Cheng (Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States)

Elissavet Kardami (Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, University of Manitoba, Winnipeg, MB, Canada)

Y. Peng Loh (Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 14 weeks

 

Abstract | Full Text

Astrocytes are the most abundant type of glial cells in the brain, and they play a key role in Alzheimer’s disease (AD). Fibroblast Growth Factor-2 (FGF-2) has been implicated as a potential therapeutic agent for treating AD. In the present study, we investigated the protective effects of low molecular weight (LMW; 17 KDa) and high molecular weight (HMW; 23 KDa) forms of FGF-2 on Aβ1–42-induced toxicity, and proliferation in astrocytes. We show that both isoforms of FGF-2 have similar protective effects against Aβ1–42-induced cytotoxicity in primary cultured cortical astrocytes as measured by Lactate Dehydrogenase (LDH) release assay. Additionally, 17 KDa FGF-2 significantly promoted astrocyte proliferation as measured by Trypan Blue, DRAQ5 and 5-ethynyl-2’-deoxyuridine (EdU) staining, but not 23 kDa FGF-2. Furthermore, our results demonstrated that AKT signaling pathway was required for the protective and proliferative effects of FGF-2. Downstream effector studies indicated that 17 kDa FGF-2 promoted astrocyte proliferation by enhanced expression of c-Myc, Cyclin D1, Cyclin E. Furthermore, our data suggested that Cyclin D1 was required for the proliferative effect of LMW FGF2 in astrocytes. Taken together, our findings provide important information for the similarities and differences between 23 kDa and17 kDa isoforms of FGF-2 on astrocyte survival and proliferation.