PMID- 14552887
OWN - NLM
STAT- MEDLINE
DCOM- 20031031
LR  - 20190722
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 183
IP  - 2
DP  - 2003 Oct
TI  - Neurotrophins regulate proliferation and survival of two microglial cell lines in 
      vitro.
PG  - 469-81
AB  - 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.
FAU - Zhang, Jianmin
AU  - Zhang J
AD  - Department of Anatomical Sciences and Neurobiology, University of Louisville 
      School of Medicine, Louisville, Louisville, KY 40292, USA.
FAU - Geula, Changiz
AU  - Geula C
FAU - Lu, Chengliang
AU  - Lu C
FAU - Koziel, Henry
AU  - Koziel H
FAU - Hatcher, Linda M
AU  - Hatcher LM
FAU - Roisen, Fred J
AU  - Roisen FJ
LA  - eng
GR  - 1P20RR15576-01/RR/NCRR NIH HHS/United States
GR  - AG14706/AG/NIA NIH HHS/United States
GR  - F32 HL71372/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antigens, Surface)
RN  - 0 (Avian Proteins)
RN  - 0 (Blood Proteins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Bsg protein, Gallus gallus)
RN  - 0 (Bsg protein, mouse)
RN  - 0 (Bsg protein, rat)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Receptor, Nerve Growth Factor)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 136894-56-9 (Basigin)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - Animals
MH  - *Antigens, CD
MH  - *Antigens, Neoplasm
MH  - *Antigens, Surface
MH  - *Avian Proteins
MH  - Basigin
MH  - *Blood Proteins
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Cell Count
MH  - Cell Division/drug effects/physiology
MH  - Cell Line
MH  - Cell Survival/drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - Membrane Glycoproteins/biosynthesis
MH  - Mice
MH  - Microglia/cytology/*drug effects/*physiology
MH  - Nerve Growth Factor/pharmacology
MH  - Nerve Growth Factors/*pharmacology
MH  - Neurotrophin 3/pharmacology
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Receptor, Nerve Growth Factor
MH  - Receptor, trkA/biosynthesis
MH  - Receptor, trkB/biosynthesis
MH  - Receptors, Nerve Growth Factor/biosynthesis
EDAT- 2003/10/14 05:00
MHDA- 2003/11/01 05:00
CRDT- 2003/10/14 05:00
PHST- 2003/10/14 05:00 [pubmed]
PHST- 2003/11/01 05:00 [medline]
PHST- 2003/10/14 05:00 [entrez]
AID - S001448860300222X [pii]
AID - 10.1016/s0014-4886(03)00222-x [doi]
PST - ppublish
SO  - Exp Neurol. 2003 Oct;183(2):469-81. doi: 10.1016/s0014-4886(03)00222-x.