CoChat
Sign Up
Cited by 146Parkinson's Disease Mechanisms and TreatmentsNerve injury and regenerationNuclear Receptors and Signaling

Astrocytes retrovirally transduced with BDNF elicit behavioral improvement in a rat model of Parkinson’s disease

Open access
Yoshimoto, Yusuke, Lin, Qing, Collier, Timothy J., Frim, David M., Breakefield, Xandra O., Bohn, Martha C.·1995·Brain Research
DOI 10.1016/0006-8993(95)00596-i
Open this paper in CoChat — free account

Abstract

Neurotrophic factors that improve the survival of specific neuronal types during development and after exposure to various neuronal insults hold potential for treatment of neurodegenerative diseases. In particular, brain-derived neurotrophic factor (BDNF) has been shown to exert trophic and protective effects on dopaminergic neurons, the cell type known to degenerate in Parkinson's disease. To determine whether increased levels of biologically produced BDNF affect the function or regeneration of damaged dopaminergic neurons, the effects of grafting astrocytes transduced with the human BDNF gene into the striatum of the partially lesioned hemiparkinsonian rat were examined. Replication deficient retroviruses carrying either human prepro-BDNF or human alkaline phosphatase (AP) cDNA were used to transduce primary type 1 astrocytes purified from neonatal rat cortex. In vitro, BDNF mRNA was expressed by BDNF transduced astrocytes (BDNF astrocytes), but not control AP transduced astrocytes (AP astrocytes), as determined by reverse transcription polymerase chain reaction (RT-PCR). The modified astrocytes were injected into the right striatum 15 days after partial lesioning of the right substantia nigra with 6-hydroxydopamine. Transplantation of BDNF astrocytes, but not AP astrocytes, significantly attenuated amphetamine-induced rotation by 45% 32 days after grafting. Apomorphine-induced rotation increased over time in both groups, but was not significantly different in the BDNF-treated group. The modified BDNF astrocytes survived well with non-invasive growth in the brain for up to 42 days. Although BDNF mRNA positive cells were not detected within the graft site using in situ hybridization, alkaline phosphatase immunoreactive (IR) cells were present in control graft sites suggesting that the retroviral construct continued to be expressed at 42 days. Analysis of the density of tyrosine hydroxylase (TH)-IR fibers showed no effect of BDNF on TH-IR fiber density in the striatum on the lesioned side. These findings suggest that ex vivo gene therapy with BDNF ameliorates parkinsonian symptoms through a mechanism(s) other than one involving an effect of BDNF on regeneration or sprouting from dopaminergic neurons.

Integrity signals

Registry

Crossref · 10.1016/0006-8993(95)00596-i

Cites

75 of 75 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • When induction of parkinsonism by 6-OHDA lesion was followed by BDNF treatment, there seemed to be no recovery of the dopaminergic neuron number in substantia nigra.

    “Similarly controversial results were obtained when induction of parkinsonism by 6-OHDA lesion was followed by BDNF treatment. There seemed to be no recovery of the dopaminergic neurons number in SN [92,95,97,98].”

    From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [98]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Yoshimoto, Y., Lin, Q., Collier, T. J., Frim, D. M., Breakefield, X. O., & Bohn, M. C.
Affiliations
  • University of Rochester Medicine (US)
  • Harvard University (US)
Corresponding author
Bohn, Martha C.
ORCID
Venue
Brain Research
Publisher
Elsevier BV
Published
1995-09
Volume
691
Issue
1-2
Pages
25-36
ISSN
0006-8993 (ISSN-L)
DOI
10.1016/0006-8993(95)00596-i
OpenAlex
W2037892763
Cited by
146
References
75
Citations by year
2025: 1 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 1 · 2015: 6 · 2014: 2 · 2013: 3 · 2012: 4
FWCI
9.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Research (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
brain-derived neurotrophic factor, Parkinson's disease, astrocyte transplantation, ex vivo gene therapy, retroviral transduction, dopaminergic neurons, 6-hydroxydopamine lesion, substantia nigra, striatum, amphetamine-induced rotation, apomorphine-induced rotation, tyrosine hydroxylase, neuroprotection
MeSH terms
Amphetamine, Animals, Apomorphine, Astrocytes, Disease Models, Animal, Genetic Vectors, Humans, Male, Nerve Fibers, Nerve Growth Factors, Nerve Tissue Proteins, Parkinson Disease, Secondary, Rats, Inbred F344, Retroviridae, Rotation, Transduction, Genetic, Brain-Derived Neurotrophic Factor, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review