Neurotensin-polyplex-mediated brain-derived neurotrophic factor gene delivery into nigral dopamine neurons prevents nigrostriatal degeneration in a rat model of early Parkinson’s disease
Open accessAbstract
BACKGROUND: The neurotrophin Brain-Derived Neurotrophic Factor (BDNF) influences nigral dopaminergic neurons via autocrine and paracrine mechanisms. The reduction of BDNF expression in Parkinson's disease substantia nigra (SN) might contribute to the death of dopaminergic neurons because inhibiting BDNF expression in the SN causes parkinsonism in the rat. This study aimed to demonstrate that increasing BDNF expression in dopaminergic neurons of rats with one week of 6-hydroxydopamine lesion recovers from parkinsonism. The plasmids phDAT-BDNF-flag and phDAT-EGFP, coding for enhanced green fluorescent protein, were transfected using neurotensin (NTS)-polyplex, which enables delivery of genes into the dopaminergic neurons via neurotensin-receptor type 1 (NTSR1) internalization. RESULTS: Two weeks after transfections, RT-PCR and immunofluorescence techniques showed that the residual dopaminergic neurons retain NTSR1 expression and susceptibility to be transfected by the NTS-polyplex. phDAT-BDNF-flag transfection did not increase dopaminergic neurons, but caused 7-fold increase in dopamine fibers within the SN and 5-fold increase in innervation and dopamine levels in the striatum. These neurotrophic effects were accompanied by a significant improvement in motor behavior. CONCLUSIONS: NTS-polyplex-mediated BDNF overexpression in dopaminergic neurons has proven to be effective to remit hemiparkinsonism in the rat. This BDNF gene therapy might be helpful in the early stage of Parkinson's disease.
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BDNF administration recovers spontaneous motor behavior in the rat model of Parkinson's disease.
“It was also shown that the BDNF administration recovers spontaneous motor behavior in the rat model of PD [95].”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [95]
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 [95]
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BDNF as a Promising Therapeutic Agent in Parkinson’s Disease
Palasz, E., Wysocka, A., Gasiorowska, A., Chalimoniuk, M., Niewiadomski, W., & Niewiadomska, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21031170 · Cited by 504 · see citing works
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- Authors
- Hernandez-Chan, N. G., Bannon, M. J., Orozco-Barrios, C. E., Escobedo, L., Zamudio, S., De la Cruz, F., Gongora-Alfaro, J. L., Armendáriz-Borunda, J., Reyes-Corona, D., Espadas-Alvarez, A. J., Flores-Martínez, Y. M., Ayala-Davila, J., Hernandez-Gutierrez, M. E., Pavón, L., García-Villegas, R., Nadella, R., & Martinez-Fong, D.
- Affiliations
- Wayne State University (US)
- Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (MX)
- Instituto Politécnico Nacional (MX)
- Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz (MX)
- ORCID
- Venue
- Journal of Biomedical Science
- Published
- 2015-07-22
- Volume
- 22
- Issue
- 1
- Pages
- 59-59
- ISSN
- 1021-7770 (ISSN-L)
- 1423-0127
- PMC
- PMC4511027
- OpenAlex
- W1893133681
- Cited by
- 73
- References
- 74
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 9 · 2023: 9 · 2022: 9 · 2021: 9 · 2020: 6 · 2019: 6 · 2018: 11 · 2017: 6 · 2016: 2
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Journal of Biomedical Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (R01DA006470, DA006470)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- brain-derived neurotrophic factor, gene therapy, Parkinson's disease, substantia nigra, dopaminergic neurons, 6-hydroxydopamine lesion, nigrostriatal degeneration, BDNF overexpression, dopamine innervation, striatum, motor behavior, neurotrophins
- MeSH terms
- Animals, Disease Models, Animal, Male, Neurotensin, Parkinson Disease, Substantia Nigra, Transfection, Genetic Therapy, Rats, Wistar, Receptors, Neurotensin, Brain-Derived Neurotrophic Factor, Rats, Dopaminergic Neurons
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