PMID- 8635559
OWN - NLM
STAT- MEDLINE
DCOM- 19960711
LR  - 20091119
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 139
IP  - 1
DP  - 1996 May
TI  - Intraparenchymal NGF injections in adult and aged rats induce long-lasting Trk 
      tyrosine phosphorylation.
PG  - 121-30
AB  - Neurotrophic factors, particularly the neurotrophins nerve growth factor (NGF) 
      and brain-derived neurotrophic factor (BDNF) and related molecules are proposed 
      for the experimental treatment of neurode-generative disease. Earlier 
      observations had suggested down-regulation of the neurotrophin receptor response 
      with chronic stimulation. We therefore tested for effects of acute and chronic 
      NGF treatment in vivo on the tyrosine phosphorylation response of Trk-type 
      neurotrophin receptors in adult and aged rats. Rats were treated for 1 week with 
      daily injections of NGF directly into the striatum. Surprisingly, this chronic 
      neurotrophin treatment induced long-lasting tyrosine phosphorylation of Trk type 
      receptors beyond the last injection. A similar result was obtained with 1 week of 
      daily injections of BDNF into the hippocampus. Persistent TRK tyrosine 
      phosphorylation was also observed after single neurotrophin injections. With 1 
      microgram of NGF injected, Trk-type receptors were maximally stimulated from 
      immediately after the injection until 3 days after the treatment. Maintaining Trk 
      tyrosine phosphorylation required maintained energy levels in the tissue. 
      Incubation of microslices of brain tissue from NGF-injected animals in 
      glucose-free buffer completely abolished all Trk tyrosine phosphorylation 
      signals. Recovery of tissue in presence of glucose restored the signals in 
      microslices derived from NGF-injected animals, in absence of acute NGF treatment. 
      This result, together with dose-response comparisons after 2-h and 2-day survival 
      times suggest that Trk protein remains tyrosine phosphorylated due to trophic 
      protein which is only slowly being cleared out of the tissue during several days 
      after the injection. Experiments with aged rats indicated similar extent and 
      duration of Trk receptor activation after NGF administration in young adult and 
      in aged brain.
FAU - Knusel, B
AU  - Knusel B
AD  - Division of Neurogerontology, Andrus Gerontology Center, University of Southern 
      California, Los Angeles 90089, USA.
FAU - Kaplan, D R
AU  - Kaplan DR
FAU - Hefti, F
AU  - Hefti F
LA  - eng
GR  - AG09793/AG/NIA NIH HHS/United States
GR  - AG10480./AG/NIA NIH HHS/United States
GR  - NS22933/NS/NINDS 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 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Age Factors
MH  - Aging/*drug effects/metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor
MH  - Female
MH  - Hippocampus/drug effects/enzymology
MH  - Humans
MH  - Microinjections
MH  - Nerve Growth Factors/*pharmacology
MH  - Nerve Tissue Proteins/*pharmacology
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Inbred F344
MH  - Rats, Wistar
MH  - Receptor Protein-Tyrosine Kinases/*drug effects/metabolism
MH  - Time Factors
EDAT- 1996/05/01 00:00
MHDA- 1996/05/01 00:01
CRDT- 1996/05/01 00:00
PHST- 1996/05/01 00:00 [pubmed]
PHST- 1996/05/01 00:01 [medline]
PHST- 1996/05/01 00:00 [entrez]
AID - S0014-4886(96)90087-4 [pii]
AID - 10.1006/exnr.1996.0087 [doi]
PST - ppublish
SO  - Exp Neurol. 1996 May;139(1):121-30. doi: 10.1006/exnr.1996.0087.