PMID- 11183872
OWN - NLM
STAT- MEDLINE
DCOM- 20001109
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 75
IP  - 5
DP  - 2000 Nov
TI  - Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 prevent 
      the death of striatal projection neurons in a rodent model of Huntington's 
      disease.
PG  - 2190-9
AB  - Intrastriatal injection of quinolinate has been proven to be a very useful animal 
      model to study the pathogenesis and treatment of Huntington's disease. To 
      determine whether growth factors of the neurotrophin family are able to prevent 
      the degeneration of striatal projection neurons, cell lines expressing 
      brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or 
      neurotrophin-4/5 (NT-4/5) were grafted in the adult rat striatum before 
      quinolinate injection. Three days after lesioning, ongoing cell death was 
      assessed by in situ detection of DNA fragmentation. In animals grafted with the 
      control cell line, quinolinate injection induced a gradual cell loss that was 
      differentially prevented by intrastriatal grafting of BDNF-, NT-3-, or 
      NT-415-secreting cells. Seven days after lesioning, we characterized striatal 
      projection neurons that were protected by neurotrophins. Quinolinate injection, 
      alone or in combination with the control cell line, induced a selective loss of 
      striatal projection neurons. Grafting of a BDNF-secreting cell line pre-vented 
      the loss of all types of striatal projection neurons analyzed. Glutamic acid 
      decarboxylase 67-, preproenkephalin-, and preprotachykinin A- but not 
      prodynorphin-expressing neurons were protected by grafting of NT-3- or 
      NT-4/5-secreting cells but with less efficiency than the BDNF-secreting cells. 
      Our findings show that neurotrophins are able to promote the survival of striatal 
      projection neurons in vivo and suggest that BDNF might be beneficial for the 
      treatment of striatonigral degenerative disorders, including Huntington's 
      disease.
FAU - Perez-Navarro, E
AU  - Perez-Navarro E
AD  - Departament de Biologia Cel.lular i Anatomia Patologica, Facultat de Medicina, 
      IDIBAPS, Universitat de Barcelona, Spain.
FAU - Canudas, A M
AU  - Canudas AM
FAU - Akerund, P
AU  - Akerund P
FAU - Alberch, J
AU  - Alberch J
FAU - Arenas, E
AU  - Arenas E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enkephalins)
RN  - 0 (Isoenzymes)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Protein Precursors)
RN  - 0 (Tachykinins)
RN  - 0 (preprotachykinin)
RN  - 145172-44-7 (neurotrophin 5)
RN  - 93443-35-7 (preproenkephalin)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
RN  - EC 4.1.1.15 (glutamate decarboxylase 1)
RN  - F6F0HK1URN (Quinolinic Acid)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/metabolism/*pharmacology
MH  - Cell Death/drug effects
MH  - Cell Line
MH  - Cell Transplantation
MH  - Corpus Striatum/*drug effects/metabolism/pathology
MH  - Disease Models, Animal
MH  - Enkephalins/biosynthesis
MH  - Fibroblasts/metabolism/transplantation
MH  - Glutamate Decarboxylase/biosynthesis
MH  - Huntington Disease/*drug therapy/metabolism/pathology
MH  - Isoenzymes/biosynthesis
MH  - Male
MH  - Nerve Growth Factors/biosynthesis/*pharmacology
MH  - Neurons/*drug effects/metabolism/pathology
MH  - Neurotrophin 3/biosynthesis/pharmacology
MH  - Phosphorylation/drug effects
MH  - Protein Precursors/biosynthesis
MH  - Quinolinic Acid
MH  - Rats
MH  - Rats, Inbred F344
MH  - Receptor, trkB/metabolism
MH  - Tachykinins/biosynthesis
EDAT- 2001/02/24 12:00
MHDA- 2001/02/28 10:01
CRDT- 2001/02/24 12:00
PHST- 2001/02/24 12:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2001/02/24 12:00 [entrez]
AID - 10.1046/j.1471-4159.2000.0752190.x [doi]
PST - ppublish
SO  - J Neurochem. 2000 Nov;75(5):2190-9. doi: 10.1046/j.1471-4159.2000.0752190.x.