PMID- 8613721
OWN - NLM
STAT- MEDLINE
DCOM- 19960606
LR  - 20220409
IS  - 0270-6474 (Print)
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 15
IP  - 12
DP  - 1995 Dec
TI  - Intrastriatal implantation of fibroblasts genetically engineered to produce 
      brain-derived neurotrophic factor prevents degeneration of dopaminergic neurons 
      in a rat model of Parkinson's disease.
PG  - 7810-20
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by a 
      progressive loss of the dopaminergic neurons of the substantia nigra pars 
      compacta (SNpc). Although various treatments are successfully used to alleviate 
      the symptoms of PD, none of them prevents or halts the neurodegenerative process 
      of the disease. Brain-derived neurotrophic factor (BDNF), a member of the 
      neurotrophin family of proteins, supports the survival and the differentiation of 
      dopaminergic neurons. BDNF also prevents the death of dopaminergic neurons in 
      vitro, which suggests that it may be of possible use in the development of 
      neuroprotective therapies for PD. To determine whether BDNF is neuroprotective 
      for SNpc dopaminergic neurons in the adult brain, we used a rat model of PD in 
      which degeneration of 60-70% of these neurons was induced by an intrastriatal 
      injection of 6-hydroxydopamine (6-OHDA). We report here that intrastriatal grafts 
      of fibroblasts genetically engineered to produce BDNF partially prevent the loss 
      of nerve terminals and completely prevent the loss of cell bodies of the 
      nigrostriatal dopaminergic pathway that is induced by the intrastriatal injection 
      of 6-OHDA. In contrast, the implantation of control fibroblasts that did not 
      produce BDNF failed to protect nerve terminals and cell bodies against 
      6-OHDA-induced damage. Our observation that grafts of BDNF-producing fibroblasts 
      protect against 6-OHDA-induced degeneration of SNpc dopaminergic neurons in the 
      adult rat brain opens new perspectives for treatments aimed at the prevention of 
      neurodegeneration in PD, using gene therapy and neurotrophic factors such as 
      BDNF.
FAU - Levivier, M
AU  - Levivier M
AD  - Department of Neurology, Columbia University, New York, New York 10032, USA.
FAU - Przedborski, S
AU  - Przedborski S
FAU - Bencsics, C
AU  - Bencsics C
FAU - Kang, U J
AU  - Kang UJ
LA  - eng
GR  - 1-K08-NS01724-01/NS/NINDS NIH HHS/United States
GR  - R29-NS32080/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Autoradiography
MH  - Brain-Derived Neurotrophic Factor
MH  - Corpus Striatum/drug effects/*pathology/physiopathology
MH  - Dopamine/*physiology
MH  - Fibroblasts/*metabolism/*transplantation
MH  - Genetic Engineering
MH  - Male
MH  - Nerve Degeneration
MH  - Nerve Growth Factors/metabolism
MH  - Nerve Tissue Proteins/*metabolism
MH  - Neurons/pathology/physiology
MH  - Oxidopamine/pharmacology
MH  - Parkinson Disease/*pathology/physiopathology
MH  - Rats
MH  - Rats, Inbred F344
PMC - PMC6577965
EDAT- 1995/12/01 00:00
MHDA- 1995/12/01 00:01
PMCR- 1996/06/01
CRDT- 1995/12/01 00:00
PHST- 1995/12/01 00:00 [pubmed]
PHST- 1995/12/01 00:01 [medline]
PHST- 1995/12/01 00:00 [entrez]
PHST- 1996/06/01 00:00 [pmc-release]
AID - 10.1523/JNEUROSCI.15-12-07810.1995 [doi]
PST - ppublish
SO  - J Neurosci. 1995 Dec;15(12):7810-20. doi: 10.1523/JNEUROSCI.15-12-07810.1995.