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. 2020 May 26;12(6):1551.
doi: 10.3390/nu12061551.

Propolis as A Potential Disease-Modifying Strategy in Parkinson's Disease: Cardioprotective and Neuroprotective Effects in the 6-OHDA Rat Model

Valeria C Gonçalves  1 , Daniel J L L Pinheiro  1 , Tomás de la Rosa  1 , Antônio-Carlos G de Almeida  2 , Fúlvio A Scorza  1 , Carla A Scorza  1
Affiliations

Propolis as A Potential Disease-Modifying Strategy in Parkinson's Disease: Cardioprotective and Neuroprotective Effects in the 6-OHDA Rat Model

Valeria C Gonçalves et al. Nutrients. .

Abstract

Patients with Parkinson's disease (PD) manifest nonmotor and motor symptoms. Autonomic cardiovascular dysregulation is a common nonmotor manifestation associated with increased morbimortality. Conventional clinical treatment alleviates motor signs but does not change disease progression and fails in handling nonmotor features. Nutrition is a key modifiable determinant of chronic disease. This study aimed to assess the effects of propolis on cardiological features, heart rate (HR) and heart rate variability (HRV) and on nigrostriatal dopaminergic damage, detected by tyrosine hydroxylase (TH) immunoreactivity, in the 6-hydroxydopamine (6-OHDA) rat model of PD. Male Wistar rats were injected bilaterally with 6-OHDA or saline into the striatum and were treated with propolis or water for 40 days. Autonomic function was assessed by time domain parameters (standard deviation of all normal-to-normal intervals (SDNN) and square root of the mean of the squared differences between adjacent normal RR intervals (RMSSD)) of HRV calculated from electrocardiogram recordings. Reductions in HR (p = 1.47×10-19), SDNN (p = 3.42×10-10) and RMSSD (p = 8.2×10-6) detected in parkinsonian rats were reverted by propolis. Propolis attenuated neuronal loss in the substantia nigra (p = 5.66×10-15) and reduced striatal fiber degeneration (p = 7.4×10-5) in 6-OHDA-injured rats, which also showed significant weight gain (p = 1.07×10-5) in comparison to 6-OHDA-lesioned counterparts. Propolis confers cardioprotection and neuroprotection in the 6-OHDA rat model of PD.

Keywords: 6-OHDA; Parkinson’s disease; propolis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic figure of the 6-hydroxydopamine (6-OHDA)-induced bilateral striatal lesion. (A) Animal fixed to stereotactic apparatus receiving injection of the neurotoxin by Hamilton syringe. (B) Rat skull, the arrows indicate the anthropometric points (lambda and bregma). (C) Rat brain, the arrows indicate the points referring to the stereotactic coordinates used for bilateral injection of 6-OHDA into the striatum. Picture created on the Mind the Graph platform (mindthegraph.com) under free license.
Figure 2
Figure 2
Schematic figure of the cardiac lead implantation and signal analysis. (A) Suture indicating the location of the xiphoid process and sternocleidomastoid musculature. (B) The acrylic structure in the rat skullcap with the cardiac electrode output connected to the electrocardiogram (ECG) register acquisition equipment. The red lines indicate the cardiac electrode wires placed subcutaneously. (C) Cardiac lead output connected to the biological signal amplifier with output for PowerLab v8 data digitizer and representative electrocardiographic record. (D) Identification of the amplitude of each R point of the analyzed stretch represented by the yellow dot. (E) Tachograph of R-R points. Vertical lines identify the R peaks. The distance between the lines on the x-axis represents the distance R-R. The height, on the y-axis, represents the maximum amplitude of the R peak. (F) Average heart rate, standard deviation of all normal-to-normal intervals (SDNN), and square root of the mean of the squared differences between adjacent normal RR intervals (RMSSD) dispersion of each stretch analyzed by group of animals. Picture created on the Mind the Graph platform (mindthegraph.com) under free license.
Figure 3
Figure 3
Representative schematic of the major experimental steps to assess nigrostriatal dopaminergic death. (A) Transcardiac perfusion: animal with exposed rib cage. The insert shows the heart with a cut in the right atrium for drainage of infused solutions, represented by the red line, and needle in the left ventricle for the entrance of the perfusion solutions. (B) Infusion pump set to move 9 mL/s to deliver phosphate buffered saline (PBS) solution and then paraformaldehyde (PFA). (C) The skullcap was removed for exposure and removal of the brain. (D) Brain was coronally sliced in a cryostat at 40 µm under a temperature of −24 °C. (E) Representative image of the positive TH-stained slices after immunohistochemistry protocol. (F) Quantification of the percentage of dopaminergic death in striatum and in substantia nigra pars compacta (SNc) using Image J software.
Figure 4
Figure 4
Representative 4 s epoch of the ECG recordings. (A) Sham; (B) 6-OHDA; (C) sham + P; (D) 6-OHDA + P.
Figure 5
Figure 5
Boxplot of heart rate and heart rate variability parameters (SDNN and RMSS). The interquartile range in the graphs is indicated by the size of the boxes; the confidence interval for median is represented by the chamfer; the statistically significant difference between two groups is indicated by the asterisks; data with values outside the interquartile range are represented by the red ‘+’ symbol. Median and confidence interval for HR, SDNN, and RMSSD were as follows: (A) HR: 339.1 ± 8.3 (sham), 359.2 ± 9.3 (sham + P), 306.7 ± 4.8 (6-OHDA), 323.2 ± 4.8 (6-OHDA + P); (B) SDNN: 0.008632 ± 0.001508 (sham), 0.01025 ± 0.00154 (sham + P), 0.005022 ± 0.000605 (6-OHDA), 0.007386 ± 0.001517 (6-OHDA + P); (C) RMSSD: 0.006963 ± 0.002125 (sham), 0.007532 ± 0.003008 (sham + P), 0.003804 ± 0.000501 (6-OHDA), 0.00499 ± 0.001705 (6-OHDA + P).
Figure 6
Figure 6
Histograms showing distribution of R-R intervals by length range. (A) sham: RR interval from 0.12 to 0.206 s; (B) 6-OHDA: RR interval from 0.175 to 0.237 s; (C) sham + P: RR interval from 0.095 to 0.212 s; (D) 6-OHDA + P: interval RR of 0.15 to 0.212 s.
Figure 7
Figure 7
Representative striatum images of tyrosine hydroxylase (TH)-immunoreactive sections. TH-positive striatal fibers in (A) sham; (B) 6-OHDA; (C) sham + P; (D) 6-OHDA + P.
Figure 8
Figure 8
Representative SNc images of TH-immunoreactive sections. TH-positive dopaminergic neurons in the SNc in (A) sham; (B) 6-OHDA; (C) sham + P; (D) 6-OHDA + P.
Figure 9
Figure 9
Boxplot of the TH immunohistochemistry. The interquartile range in the graphs is indicated by the size of the boxes; the confidence interval for median is represented by the chamfer; the statistically significant difference between two groups is indicated by the asterisks. (A) Optical density of the TH-positive fibers in the striatum; median and confidence interval were as follows: 2.4949 × 10+5 ± 0.214 × 10+5 (sham); 2.927 × 10+5 ± 0.243 × 10+5 (sham + P); 2.356 × 10+5 ± 0.084 × 10+5 (6-OHDA + P); 2.189 × 10+5 ± 0.087 × 10+5 (6-OHDA). (B) TH-positive neuronal nuclei in the SNc; median and confidence interval were as follows: 996 ± 119 (sham); 964 ± 126 (sham + P); 821 ± 166.5 (6-OHDA + P); 463.5 ± 90.6 (6-OHDA).
Figure 10
Figure 10
Statistical analysis of evolution of animal weights during the experimental period of 40 days. (A) Average weight with standard deviation (groups: sham, n = 13; sham + P, n = 13; 6-OHDA, n = 9; 6-OHDA + P, n = 9). The asterisks indicate a significant difference between groups (* p < 0.05). Day 0: chi-square = 2.2876, p = 0.5149; day 7: chi-square = 5.4888, p = 0.1393; day 14: chi-square = 14.8267, p = 0.0019709; day 21: chi-square = 17.6751, p = 0.00051; day 28: chi-square = 19.057, p = 0.000266; day 34: chi-square = 25.7706, p = 0.00001065; day 40: chi-square = 25.7568, p = 0.0000107. (B) Distribution of the animals’ body weight of all groups on the first day of measurement. The mean and standard deviation were as follows: 311.3 ± 4.392 (sham); 310.2 ± 6.9 (sham + P); 307.7 ± 10.2 (6-OHDA); 313.7 ± 11.11 (6-OHDA + P). (C) Distribution of the animals’ body weight of all groups on day 40 of measurement. The mean and standard deviation were as follows: 428.8 ± 26.6 (sham); 434.2 ± 27.13 (sham + P); 374.7 ± 11.15 (6-OHDA); 392.8 ± 9.704 (6-OHDA + P).
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References

    1. Saito Y., Nishio K., Ogawa Y., Kinumi T., Yoshida Y., Masuo Y., Niki E. Molecular mechanisms of 6-hydroxydopamine-induced cytotoxicity in PC12 cells: Involvement of hydrogen peroxide-dependent and -independent action. Free Radic. Biol. Med. 2007;42:675–685. doi: 10.1016/j.freeradbiomed.2006.12.004. - DOI - PubMed
    1. Kalia L.V., Lang A.E. Parkinson’s disease. Lancet. 2015;386:896–912. doi: 10.1016/S0140-6736(14)61393-3. - DOI - PubMed
    1. Kontis V., Bennett J.E., Mathers C.D., Li G., Foreman K., Ezzati M. Future life expectancy in 35 industrialised countries: Projections with a Bayesian model ensemble. Lancet. 2017;389:1323–1335. doi: 10.1016/S0140-6736(16)32381-9. - DOI - PMC - PubMed
    1. Wanneveich M., Moisan F., Jacqmin-Gadda H., Elbaz A., Joly P. Projections of prevalence, lifetime risk, and life expectancy of Parkinson’s disease (2010–2030) in France. Mov. Disord. 2018;33:1449–1455. doi: 10.1002/mds.27447. - DOI - PubMed
    1. Postuma R.B., Berg D., Adler C.H., Bloem B.R., Chan P., Deuschl G., Stern M. The new definition and diagnostic criteria of Parkinson’s disease. Lancet Neurol. 2016;15:546–548. doi: 10.1016/S1474-4422(16)00116-2. - DOI - PubMed