Abstract
Aim:
To investigate the protective effects of octacosanol in 6-hydroxydopamine-induced Parkinsonian rats and find whether octacosanol has effects on pro nerve growth factor (pro-NGF), NGF and the downstream effector proteins.
Methods:
Behavioral tests, enzymatic assay, tyrosine hydroxylase immunohistochemistry, TUNEL and Western blot were used to investigate the effects of octacosanol in this rat model of PD.
Results:
Oral administration of octacosanol (35–70 mg/kg, po for 14 d) significantly improved the behavioral impairments in rats induced by 6-OHDA and dose-dependently preserved the free radical scavenging capability of the striatum. Octacosanol treatment also effectively ameliorated morphological appearances of TH-positive neuronal cells in nigrostriatal systems and decreased the apoptotic cells induced by 6-OHDA in striatum. In addition, octacosanol strikingly blocked the 6-OHDA-induced increased expression of proNGF-p75NTR-sortilin death signaling complex and its downstream effector proteins. Meantime, octacosanol prevented the decreased levels of NGF, its receptors TrkA and p-Akt which together mediated the cell survival pathway.
Conclusion:
The findings implicated that the anti-parkinsonism effects afforded by octacosanol might be mediated by its neuro-microenvironment improving potency through retrieving the ratios of proNGF:NGF and the respective receptors p75NTR:TrkA in vivo. Due to its excellent tolerability and non-toxicity, octacosanol may be a promising agent for PD treatment.
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Abbreviations
- 6-OHDA:
-
6-hydroxydopamine
- AD:
-
Alzheimer's disease
- BSA:
-
bovine serum albumin
- CMC:
-
carboxymethylcellulose sodium
- CAT:
-
catalase
- DA:
-
dopamine
- DAB:
-
3,3′-diaminobenzidine
- GSH-Px:
-
glutathione peroxidase
- JNK:
-
Jun kinase
- L-dopa:
-
levodopa
- MDA:
-
malondialdehyde
- NGF:
-
nerve growth factor
- Ocs:
-
Octacosanol
- PBS:
-
phosphate buffered saline
- PD:
-
Parkinson's disease
- ProNGF:
-
precursor of nerve growth factor
- prot.:
-
protein
- ROS:
-
reactive oxygen species
- SN:
-
substantia nigra
- SOD:
-
superoxide dismutase
- TH:
-
tyrosine hydroxylase
- TUNEL:
-
Terminal deoxynucleotidyl transferase-mediated dUTP Nick End Labeling assay
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Acknowledgements
This work was supported by the grant from the National Basic Research Development Program of China (2007CB507400) and National High Technology Research and Development Program of China (2006AA02A408). This research was also supported by grants from the National 973 Fundamental Project of China, Grant Number (2009CB523004), We are indebted to the grant from the Ministry of Science and Technology of China Eleventh 5-year Plan-Technical Platform for Drug Development (2009ZX09303).
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Wang, T., Liu, Yy., Wang, X. et al. Protective effects of octacosanol on 6-hydroxydopamine-induced Parkinsonism in rats via regulation of ProNGF and NGF signaling. Acta Pharmacol Sin 31, 765–774 (2010). https://doi.org/10.1038/aps.2010.69
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DOI: https://doi.org/10.1038/aps.2010.69
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