Received 7 March 2010; Accepted 13 May 2010; Published online 28 June 2010.
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.
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.
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.
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.
Parkinson's disease; oxidative stress; proNGF; nerve growth factor; neuroprotection; apoptosis; octacosanol
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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