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:
https://lup.lub.lu.se/record/115713
- author
- Gustafsson, Elin
; Andsberg, Gunnar
LU
; Darsalia, Vladimer
LU
; Mohapel, Paul
LU
; Mandel, Ronald J.
; Kirik, Deniz
LU
; Lindvall, Olle
LU
and Kokaia, Zaal
LU
- organization
- publishing date
- 2003
- 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
- 2016-04-01 12:12:50
- date last changed
- 2022-03-28 21:51:20
@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 = {{https://lup.lub.lu.se/search/files/2829540/623808.pdf}},
doi = {{10.1046/j.1460-9568.2003.02713.x}},
volume = {{17}},
year = {{2003}},
}