Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease
Abstract
:1. Introduction
2. Results
2.1. Animal Welfare Varied among Experimental Groups
2.2. Aging Does Not Affect the Impact of the Lesion on the Turning Behavior and Degree of Forelimb Use Asymmetry
2.3. Aging Affects the Impact of Lesions on Skilled Motor Function
2.4. Aging Exacerbates Lesion-Induced Dopaminergic Degeneration within SNpc
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Experimental Design
4.3. Surgical Procedure (6-Hydroxidopamine Lesion)
4.4. Animal Welfare—Body Weight Measurement
4.5. Behavioral Assessment
4.5.1. Apomorphine-Induced Rotation Test
4.5.2. Cylinder Test
4.5.3. Staircase Test
4.6. Histological Assessment
4.6.1. TH Immunohistochemistry
4.6.2. Striatal Fiber-Density Measurement
4.7. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
PD | Parkinson’s disease |
6-OHDA | 6-hydroxydopamine |
SNpc | Substantia nigra pars compacta |
DA neurons | Dopamine-containing neurons |
MFB | Medial forebrain bundle |
SEM | Standard error of the mean |
TH | Tyrosine hydroxylase |
STR | Striatum |
NADPH | Nicotinamide adenine dinucleotide phosphate |
SN | Substantia nigra |
MPTP | 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine |
BDNF | Brain-derived neurotrophic factor |
GDNF | Glial cell line-derived neurotrophic factor |
PFA | Paraformaldehyde |
PBS | Phosphate-buffered saline |
FCS | Fetal calf serum |
RT | Room temperature |
PBS-T | Phosphate-buffered saline -Triton |
DAB | 3,3’- diaminobenzidine tetrahydrochloride |
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Comparison between Groups | Mean Difference | SEM | p-Value |
---|---|---|---|
Sham aged rats vs. 6-OHDA aged rats | 7.88 | 2.40 | p = 0.019 |
Sham aged rats vs. sham young adult rats | −15.1 | 2.61 | p < 0.0001 |
Sham aged rats vs. 6-OHDA young adult rats | −4.43 | 2.46 | p = 0.410 |
6-OHDA aged rats vs. 6-OHDA young adult rats | −12.3 | 2.09 | p < 0.0001 |
Sham young adult rats vs. 6-OHDA young adult rats | 10.7 | 2.33 | p = 0.001 |
Sham young adult rats vs. 6-OHDA aged rats | 23.0 | 2.27 | p < 0.0001 |
Comparison between Groups | Mean Difference | SEM | p-Value |
---|---|---|---|
Sham aged rats vs. 6-OHDA aged rats | 71.3 | 4.78 | p < 0.0001 |
Sham aged rats vs. Sham young adult rats | −3.39 | 4.99 | 0.986 |
Sham aged rats vs. 6-OHDA young adult rats | 67.3 | 4.99 | p < 0.0001 |
6-OHDA aged rats vs. 6-OHDA young adult rats | −4.05 | 4.78 | 0.958 |
Sham young adult rats vs. 6-OHDA young adult rats | 70.7 | 4.99 | p < 0.0001 |
Sham young adult rats vs. 6-OHDA aged rats | 74.7 | 4.78 | p < 0.0001 |
Staircase | |||
Comparison between Groups | Mean Difference | SEM | p-Value |
Sham aged rats vs. 6-OHDA aged rats | 57.9 | 6.15 | p < 0.0001 |
Sham aged rats vs. sham young adult rats | 0.127 | 6.35 | p = 1.0 |
Sham aged rats vs. 6-OHDA young adult rats | 39.7 | 6.15 | p < 0.0001 |
6-OHDA aged rats vs. 6-OHDA young adult rats | −18.3 | 5.02 | p = 0.013 |
Sham young adult rats vs. 6-OHDA young adult rats | 36.6 | 5.26 | p < 0.0001 |
Sham young adult rats vs. 6-OHDA aged rats | 57.8 | 5.26 | p < 0.0001 |
Staircase–Forced-Choice | |||
Comparison between Groups | Mean Difference | SEM | p-Value |
Sham aged rats vs. 6-OHDA aged rats | 58.7 | 6.22 | p < 0.0001 |
Sham aged rats vs. sham young adult rats | 0.061 | 6.43 | p = 1.0 |
Sham aged rats vs. 6-OHDA young adult rats | 41.1 | 6.22 | p < 0.0001 |
6-OHDA aged rats vs. 6-OHDA young adult rats | −17.6 | 5.08 | p = 0.019 |
Sham young adult rats vs. 6-OHDA young adult rats | 41.1 | 5.33 | p < 0.0001 |
Sham young adult rats vs. 6-OHDA aged rats | 58.7 | 5.33 | p < 0.0001 |
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Barata-Antunes, S.; Teixeira, F.G.; Mendes-Pinheiro, B.; Domingues, A.V.; Vilaça-Faria, H.; Marote, A.; Silva, D.; Sousa, R.A.; Salgado, A.J. Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease. Int. J. Mol. Sci. 2020, 21, 3459. https://doi.org/10.3390/ijms21103459
Barata-Antunes S, Teixeira FG, Mendes-Pinheiro B, Domingues AV, Vilaça-Faria H, Marote A, Silva D, Sousa RA, Salgado AJ. Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease. International Journal of Molecular Sciences. 2020; 21(10):3459. https://doi.org/10.3390/ijms21103459
Chicago/Turabian StyleBarata-Antunes, Sandra, Fábio G. Teixeira, Bárbara Mendes-Pinheiro, Ana V. Domingues, Helena Vilaça-Faria, Ana Marote, Deolinda Silva, Rui A. Sousa, and António J. Salgado. 2020. "Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease" International Journal of Molecular Sciences 21, no. 10: 3459. https://doi.org/10.3390/ijms21103459
APA StyleBarata-Antunes, S., Teixeira, F. G., Mendes-Pinheiro, B., Domingues, A. V., Vilaça-Faria, H., Marote, A., Silva, D., Sousa, R. A., & Salgado, A. J. (2020). Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease. International Journal of Molecular Sciences, 21(10), 3459. https://doi.org/10.3390/ijms21103459