Cited by 90Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeurotransmitter Receptor Influence on Behavior

The Transfection of BDNF to Dopamine Neurons Potentiates the Effect of Dopamine D3 Receptor Agonist Recovering the Striatal Innervation, Dendritic Spines and Motor Behavior in an Aged Rat Model of Parkinson’s Disease

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Razgado-Hernandez, Luis F., Espadas-Alvarez, Armando J., Reyna-Velazquez, Patricia, Sierra-Sanchez, Arturo, Anaya-Martinez, Veronica, Jimenez-Estrada, Ismael, Bannon, Michael J., Martinez-Fong, Daniel +1 more·2015·PLOS ONE

Abstract

The progressive degeneration of the dopamine neurons of the pars compacta of substantia nigra and the consequent loss of the dopamine innervation of the striatum leads to the impairment of motor behavior in Parkinson's disease. Accordingly, an efficient therapy of the disease should protect and regenerate the dopamine neurons of the substantia nigra and the dopamine innervation of the striatum. Nigral neurons express Brain Derived Neurotropic Factor (BDNF) and dopamine D3 receptors, both of which protect the dopamine neurons. The chronic activation of dopamine D3 receptors by their agonists, in addition, restores, in part, the dopamine innervation of the striatum. Here we explored whether the over-expression of BDNF by dopamine neurons potentiates the effect of the activation of D3 receptors restoring nigrostriatal innervation. Twelve-month old Wistar rats were unilaterally injected with 6-hydroxydopamine into the striatum. Five months later, rats were treated with the D3 agonist 7-hydroxy-N,N-di-n-propy1-2-aminotetralin (7-OH-DPAT) administered i.p. during 4½ months via osmotic pumps and the BDNF gene transfection into nigral cells using the neurotensin-polyplex nanovector (a non-viral transfection) that selectively transfect the dopamine neurons via the high-affinity neurotensin receptor expressed by these neurons. Two months after the withdrawal of 7-OH-DPAT when rats were aged (24 months old), immunohistochemistry assays were made. The over-expression of BDNF in rats receiving the D3 agonist normalized gait and motor coordination; in addition, it eliminated the muscle rigidity produced by the loss of dopamine. The recovery of motor behavior was associated with the recovery of the nigral neurons, the dopamine innervation of the striatum and of the number of dendritic spines of the striatal neurons. Thus, the over-expression of BDNF in dopamine neurons associated with the chronic activation of the D3 receptors appears to be a promising strategy for restoring dopamine neurons in Parkinson's disease.

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  • Gene transfection of BDNF into a 6-hydroxydopamine-induced unilateral lesion in the striatum reverts motor deficits in an animal model of Parkinson's disease.

    “gene transfection of BDNF into a 6-hydroxydopamine-induced unilateral lesion in the striatum was able to revert motor deficits in this animal model of PD [203].”

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  1. [39]Paxinos G, Watson C (1998) The rat brain: academic press 117 p.

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Authors
Razgado-Hernandez, L. F., Espadas-Alvarez, A. J., Reyna-Velazquez, P., Sierra-Sanchez, A., Anaya-Martinez, V., Jimenez-Estrada, I., Bannon, M. J., Martinez-Fong, D., & Aceves-Ruiz, J.
Affiliations
  • Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (MX)
  • Wayne State University (US)
Corresponding author
Aceves-Ruiz, Jorge
Venue
PLOS ONE
Published
2015-02-18
Volume
10
Issue
2
Pages
e0117391
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2052299360
Cited by
90
References
83
Citations by year
2026: 4 · 2025: 1 · 2024: 7 · 2023: 5 · 2022: 14 · 2021: 8 · 2020: 15 · 2019: 5 · 2018: 8 · 2017: 13 · 2016: 8 · 2015: 2
FWCI
7.28
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Consejo Nacional de Ciencia y Tecnología (224222, 166638)
  • Consejo Nacional de Ciencia y Tecnología, Paraguay
  • National Institute on Drug Abuse (R01DA006470)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
Parkinson's disease, brain-derived neurotrophic factor, dopamine D3 receptor agonist, transfection, neurotensin receptor, substantia nigra, dendritic spines, motor behavior, 6-hydroxydopamine, aged rats, neuroprotection, non-viral gene delivery
MeSH terms
Animals, Biomechanical Phenomena, Disease Models, Animal, Gait, Male, Motor Activity, Muscles, Parkinson Disease, Psychomotor Performance, Regeneration, Transfection, Tyrosine 3-Monooxygenase, Neostriatum, Rats, Wistar, Dopamine Agonists, Brain-Derived Neurotrophic Factor, Recovery of Function, Dendritic Spines, Receptors, Dopamine D3, Rats, Dopaminergic Neurons

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