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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
- Source :
- Journal of Biomedical Science
- Publisher :
- Springer Nature
-
Abstract
- 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.
- Subjects :
- Male
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Substantia nigra
Striatum
Biology
Transfection
Gene therapy
Dopamine
Neurotrophic factors
Internal medicine
medicine
Animals
Receptors, Neurotensin
Pharmacology (medical)
Neurorestoration
Neurotrophic therapy
Neurodegeneration
Rats, Wistar
Molecular Biology
Neurotensin
Brain-derived neurotrophic factor
Biochemistry, medical
Research
Brain-Derived Neurotrophic Factor
Dopaminergic Neurons
Biochemistry (medical)
Dopaminergic
Parkinson Disease
Genetic Therapy
General Medicine
Cell Biology
medicine.disease
Rats
Substantia Nigra
Disease Models, Animal
Endocrinology
nervous system
Parkinson’s disease
biology.protein
medicine.drug
Neurotrophin
Subjects
Details
- Language :
- English
- ISSN :
- 14230127
- Volume :
- 22
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Biomedical Science
- Accession number :
- edsair.doi.dedup.....e87a92d0a9d00b3cbc8d947b7f2c3a81
- Full Text :
- https://doi.org/10.1186/s12929-015-0166-7