Advanced

Anterograde delivery of brain-derived neurotrophic factor to striatum via nigral transduction of recombinant adeno-associated virus increases neuronal death but promotes neurogenic response following stroke.

Gustafsson, Elin; Andsberg, Gunnar LU ; Darsalia, Vladimer LU ; Mohapel, Paul LU ; Mandel, Ronald J.; Kirik, Deniz LU ; Lindvall, Olle LU and Kokaia, Zaal LU (2003) In European Journal of Neuroscience 17(12). p.2667-2678
Abstract
o explore the role of brain-derived neurotrophic factor for survival and generation of striatal neurons after stroke, recombinant adeno-associated viral vectors carrying brain-derived neurotrophic factor or green fluorescent protein genes were injected into right rat substantia nigra 4–5 weeks prior to 30 min ipsilateral of middle cerebral artery occlusion. The brain-derived neurotrophic factor–recombinant adeno-associated viral transduction markedly increased the production of brain-derived neurotrophic factor protein by nigral cells. Brain-derived neurotrophic factor was transported anterogradely to the striatum and released in biologically active form, as revealed by the hypertrophic response of striatal neuropeptide Y-positive... (More)
o explore the role of brain-derived neurotrophic factor for survival and generation of striatal neurons after stroke, recombinant adeno-associated viral vectors carrying brain-derived neurotrophic factor or green fluorescent protein genes were injected into right rat substantia nigra 4–5 weeks prior to 30 min ipsilateral of middle cerebral artery occlusion. The brain-derived neurotrophic factor–recombinant adeno-associated viral transduction markedly increased the production of brain-derived neurotrophic factor protein by nigral cells. Brain-derived neurotrophic factor was transported anterogradely to the striatum and released in biologically active form, as revealed by the hypertrophic response of striatal neuropeptide Y-positive interneurons. Animals transduced with brain-derived neurotrophic factor-recombinant adeno-associated virus also exhibited abnormalities in body posture and movements, including tilted body to the right, choreiform movements of left forelimb and head, and spontaneous, so-called 'barrel' rotation along their long axis. The continuous delivery of brain-derived neurotrophic factor had no effect on the survival of striatal projection neurons after stroke, but exaggerated the loss of cholinergic, and parvalbumin- and neuropeptide Y-positive, γ-aminobutyric acid-ergic interneurons. The high brain-derived neurotrophic factor levels in the animals subjected to stroke also gave rise to an increased number of striatal cells expressing doublecortin, a marker for migrating neuroblasts, and cells double-labelled with the mitotic marker, 5-bromo-2'-deoxyuridine-5'monophosphate, and early neuronal (Hu) or striatal neuronal (Meis2) markers. Our findings indicate that long-term anterograde delivery of high levels of brain-derived neurotrophic factor increases the vulnerability of striatal interneurons to stroke-induced damage. Concomitantly, brain-derived neurotrophic factor potentiates the stroke-induced neurogenic response, at least at early stages. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Neuroscience
volume
17
issue
12
pages
2667 - 2678
publisher
Wiley-Blackwell
external identifiers
  • wos:000183732200017
  • pmid:12823474
  • scopus:0038684215
ISSN
1460-9568
DOI
10.1046/j.1460-9568.2003.02713.x
language
English
LU publication?
yes
id
d17f119d-5457-4a3a-a338-7fbbee42347e (old id 115713)
date added to LUP
2007-07-12 14:56:40
date last changed
2018-10-03 11:06:43
@article{d17f119d-5457-4a3a-a338-7fbbee42347e,
  abstract     = {o explore the role of brain-derived neurotrophic factor for survival and generation of striatal neurons after stroke, recombinant adeno-associated viral vectors carrying brain-derived neurotrophic factor or green fluorescent protein genes were injected into right rat substantia nigra 4–5 weeks prior to 30 min ipsilateral of middle cerebral artery occlusion. The brain-derived neurotrophic factor–recombinant adeno-associated viral transduction markedly increased the production of brain-derived neurotrophic factor protein by nigral cells. Brain-derived neurotrophic factor was transported anterogradely to the striatum and released in biologically active form, as revealed by the hypertrophic response of striatal neuropeptide Y-positive interneurons. Animals transduced with brain-derived neurotrophic factor-recombinant adeno-associated virus also exhibited abnormalities in body posture and movements, including tilted body to the right, choreiform movements of left forelimb and head, and spontaneous, so-called 'barrel' rotation along their long axis. The continuous delivery of brain-derived neurotrophic factor had no effect on the survival of striatal projection neurons after stroke, but exaggerated the loss of cholinergic, and parvalbumin- and neuropeptide Y-positive, γ-aminobutyric acid-ergic interneurons. The high brain-derived neurotrophic factor levels in the animals subjected to stroke also gave rise to an increased number of striatal cells expressing doublecortin, a marker for migrating neuroblasts, and cells double-labelled with the mitotic marker, 5-bromo-2'-deoxyuridine-5'monophosphate, and early neuronal (Hu) or striatal neuronal (Meis2) markers. Our findings indicate that long-term anterograde delivery of high levels of brain-derived neurotrophic factor increases the vulnerability of striatal interneurons to stroke-induced damage. Concomitantly, brain-derived neurotrophic factor potentiates the stroke-induced neurogenic response, at least at early stages.},
  author       = {Gustafsson, Elin and Andsberg, Gunnar and Darsalia, Vladimer and Mohapel, Paul and Mandel, Ronald J. and Kirik, Deniz and Lindvall, Olle and Kokaia, Zaal},
  issn         = {1460-9568},
  language     = {eng},
  number       = {12},
  pages        = {2667--2678},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Neuroscience},
  title        = {Anterograde delivery of brain-derived neurotrophic factor to striatum via nigral transduction of recombinant adeno-associated virus increases neuronal death but promotes neurogenic response following stroke.},
  url          = {http://dx.doi.org/10.1046/j.1460-9568.2003.02713.x},
  volume       = {17},
  year         = {2003},
}