Document Detail

Neurotrophins regulate proliferation and survival of two microglial cell lines in vitro.
MedLine Citation:
PMID:  14552887     Owner:  NLM     Status:  MEDLINE    
Microglia are thought to play a key role in the development and regeneration of the central nervous system although the mechanisms regulating their presence and activity are not fully understood. Substantial evidence suggests that members of the neurotrophin family such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 and -4 (NT-3/4) have a dramatic effect on both neurons and perineuronal cells. This study employed two murine microglial lines, BV-2 and N9, to examine the action of these neurotrophins on the mitotic activity and survival of microglia in vitro. Neurotrophins were incorporated into the media at the time of plating and cell number and levels of mitochondrial dehydrogenase activity (MTT) were determined at various time points in vitro. NGF increased cell number and MTT levels of both cell lines in a dose-dependent manner. BV-2 was more sensitive to NGF than N9. Similar responses were elicited by BDNF, although the sensitivity of each cell line was different than that found for NGF. NT-3 and NT-4 had no effect on cell proliferation. However, NT-4 had an effect on the survival of BV-2 and N9 cells. The response of these cells to neurotrophins was blocked by K252a, a tyrosine kinase inhibitor, suggesting that actions of neurotrophins were mediated by high-affinity tyrosine kinase receptors (Trk). Immunolocalization studies revealed positive Trk (pan) reactivity in the above cell lines and in primary microglia, but an absence of the low-affinity p75 neurotrophin receptor. Western blot analysis supported the above observations. These studies suggest that in addition to their neurotrophic actions, NGF and BDNF may also regulate microglial dynamics, thereby influencing the surrounding milieu during neuronal regeneration.
Jianmin Zhang; Changiz Geula; Chengliang Lu; Henry Koziel; Linda M Hatcher; Fred J Roisen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental neurology     Volume:  183     ISSN:  0014-4886     ISO Abbreviation:  Exp. Neurol.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-10-13     Completed Date:  2003-10-31     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0370712     Medline TA:  Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  469-81     Citation Subset:  IM    
Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, Louisville, KY 40292, USA.
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MeSH Terms
Antigens, CD*
Antigens, CD147
Antigens, Neoplasm*
Antigens, Surface*
Avian Proteins*
Blood Proteins*
Brain-Derived Neurotrophic Factor / pharmacology
Cell Count
Cell Division / drug effects,  physiology
Cell Line
Cell Survival / drug effects,  physiology
Dose-Response Relationship, Drug
Membrane Glycoproteins / biosynthesis
Microglia / cytology,  drug effects*,  physiology*
Nerve Growth Factor / pharmacology
Nerve Growth Factors / pharmacology*
Neurotrophin 3 / pharmacology
Protein-Tyrosine Kinases / metabolism
Receptor, Nerve Growth Factor
Receptor, trkA / biosynthesis
Receptor, trkB / biosynthesis
Receptors, Nerve Growth Factor / biosynthesis
Grant Support
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, Neoplasm; 0/Antigens, Surface; 0/Avian Proteins; 0/Blood Proteins; 0/Brain-Derived Neurotrophic Factor; 0/Bsg protein, Gallus gallus; 0/Bsg protein, mouse; 0/Bsg protein, rat; 0/Membrane Glycoproteins; 0/Nerve Growth Factors; 0/Neurotrophin 3; 0/Receptor, Nerve Growth Factor; 0/Receptors, Nerve Growth Factor; 136894-56-9/Antigens, CD147; 143551-63-7/neurotrophin 4; 9061-61-4/Nerve Growth Factor; EC Kinases; EC, trkA; EC, trkB

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