Protective effects of octacosanol on 6-hydroxydopamine-induced Parkinsonism in rats via regulation of ProNGF and NGF signaling.
OBJECTIVE
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.


CONCLUSIONS
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.
Wang
Tao
T
Department of Pharmacology, Institute of Basic Medical Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.
Liu
Yan-yong
YY
Wang
Xin
X
Yang
Nan
N
Zhu
Hai-bo
HB
Zuo
Ping-ping
PP
D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D005233:Fatty Alcohols / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D020932:Nerve Growth Factor / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D011498:Protein Precursors / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism
D000978:Antiparkinson Agents; D005233:Fatty Alcohols; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C514218:pro-nerve growth factor, rat; C068313:Ngfr protein, rat; C044309:1-octacosanol; D016627:Oxidopamine; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D051057:Proto-Oncogene Proteins c-akt