PMID- 10527802
OWN - NLM
STAT- MEDLINE
DCOM- 19991206
LR  - 20161124
IS  - 0969-9961 (Print)
IS  - 0969-9961 (Linking)
VI  - 6
IP  - 5
DP  - 1999 Oct
TI  - Preclinical testing of neuroprotective neurotrophic factors in a model of chronic 
      motor neuron degeneration.
PG  - 335-46
AB  - Many neurotrophic factors have been shown to enhance survival of embryonic motor 
      neurons or affect their response to injury. Few studies have investigated the 
      potential effects of neurotrophic factors on more mature motor neurons that might 
      be relevant for neurodegenerative diseases. Using organotypic spinal cord 
      cultures from postnatal rats, we have demonstrated that insulin-like growth 
      factor-I (IGF-I) and glial-derived neurotrophic factor (GDNF) significantly 
      increase choline acetyltransferase (ChAT) activity, but brain-derived 
      neurotrophic factor (BDNF), neurotrophin-4 (NT-4/5), and neurotrophin-3 (NT-3) do 
      not. Surprisingly, ciliary neurotrophic factor (CNTF) actually reduces ChAT 
      activity compared to age-matched control cultures. Neurotrophic factors have also 
      been shown to alter the sensitivity of some neurons to glutamate neurotoxicity, a 
      postulated mechanism of injury in the neurodegenerative disease, amyotrophic 
      lateral sclerosis (ALS). Incubation of organotypic spinal cord cultures in the 
      presence of the glutamate transport inhibitor threo-hydroxyaspartate (THA) 
      reproducibly causes death of motor neurons which is glutamate-mediated. In this 
      model of motor neuron degeneration, IGF-I, GDNF, and NT-4/5 are potently 
      neuroprotective, but BDNF, CNTF, and NT-3 are not. The organotypic glutamate 
      toxicity model appears to be the best preclinical predictor to date of success in 
      human clinical trials in ALS.
CI  - Copyright 1999 Academic Press.
FAU - Corse, A M
AU  - Corse AM
AD  - Department of Neurology, Johns Hopkins University School of Medicine Meyer 5-119, 
      600 North Wolfe Street, Baltimore, Maryland, 21287-7519, USA. 
      acorse@welchllink.welch.jhu.edu
FAU - Bilak, M M
AU  - Bilak MM
FAU - Bilak, S R
AU  - Bilak SR
FAU - Lehar, M
AU  - Lehar M
FAU - Rothstein, J D
AU  - Rothstein JD
FAU - Kuncl, R W
AU  - Kuncl RW
LA  - eng
GR  - K08NS01722-02/NS/NINDS NIH HHS/United States
GR  - R01NS33985-01/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  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Ciliary Neurotrophic Factor)
RN  - 0 (GDNF protein, human)
RN  - 0 (Gdnf protein, rat)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Growth Inhibitors)
RN  - 0 (Interleukin-6)
RN  - 0 (LIF protein, human)
RN  - 0 (Leukemia Inhibitory Factor)
RN  - 0 (Lymphokines)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Neurotrophin 3)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Cell Survival/drug effects
MH  - Ciliary Neurotrophic Factor/pharmacology
MH  - Fibroblast Growth Factor 2/pharmacology
MH  - Glial Cell Line-Derived Neurotrophic Factor
MH  - Growth Inhibitors/pharmacology
MH  - Humans
MH  - Insulin-Like Growth Factor I/pharmacology
MH  - *Interleukin-6
MH  - Leukemia Inhibitory Factor
MH  - Lymphokines/pharmacology
MH  - Models, Neurological
MH  - Motor Neuron Disease/*pathology/physiopathology
MH  - Motor Neurons/cytology/*drug effects/pathology
MH  - Nerve Degeneration
MH  - Nerve Growth Factors/*pharmacology/physiology
MH  - Nerve Tissue Proteins/pharmacology
MH  - Neuroprotective Agents/*pharmacology
MH  - Neurotrophin 3/pharmacology
MH  - Organ Culture Techniques
MH  - Rats
MH  - Spinal Cord/cytology/*drug effects/pathology
EDAT- 1999/10/21 00:00
MHDA- 1999/10/21 00:01
CRDT- 1999/10/21 00:00
PHST- 1999/10/21 00:00 [pubmed]
PHST- 1999/10/21 00:01 [medline]
PHST- 1999/10/21 00:00 [entrez]
AID - S0969-9961(99)90253-X [pii]
AID - 10.1006/nbdi.1999.0253 [doi]
PST - ppublish
SO  - Neurobiol Dis. 1999 Oct;6(5):335-46. doi: 10.1006/nbdi.1999.0253.