Serofendic acid prevents 6-hydroxydopamine-induced nigral neurodegeneration and drug-induced rotational asymmetry in hemi-parkinsonian rats.
Serofendic acid was recently identified as a neuroprotective factor from fetal calf serum. This study was designed to evaluate the neuroprotective effects of an intranigral microinjection of serofendic acid based on behavioral, neurochemical and histochemical studies in hemi-parkinsonian rats using 6-hydroxydopamine (6-OHDA). Rats were injected with 6-OHDA in the presence or absence of serofendic acid, or were treated with serofendic acid on the same lateral side, at 12, 24 or 72 h after 6-OHDA lesion. Intranigral injection of 6-OHDA alone induced a massive loss of tyrosine hydroxylase (TH)-immunopositive neurons in the substantia nigra pars compacta (SNpc). Either simultaneous or 12 h post-administration of serofendic acid significantly prevented both dopaminergic neurodegeneration and drug-induced rotational asymmetry. Immunoreactivities for oxidative stress markers, such as 3-nitrotyrosine (3-NT) and 4-hydroxy-2-nonenal (4-HNE), were markedly detected in the SNpc of rats injected with 6-OHDA alone. These immunoreactivities were markedly suppressed by the co-administration of serofendic acid, similar to the results in vehicle-treated control rats. In addition, serofendic acid inhibited 6-OHDA-induced alpha-synuclein expression and glial activation in the SNpc. These results suggest that serofendic acid protects against 6-OHDA-induced SNpc dopaminergic neurodegeneration in a rat model of Parkinson's disease.
Inden
Masatoshi
M
Department of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Kyoto, Japan.
Kitamura
Yoshihisa
Y
Kondo
Jun-Ichi
J
Hayashi
Kousuke
K
Yanagida
Takashi
T
Takata
Kazuyuki
K
Tsuchiya
Daiju
D
Yanagisawa
Daijiro
D
Nishimura
Kaneyasu
K
Taniguchi
Takashi
T
Shimohama
Shun
S
Sugimoto
Hachiro
H
Akaike
Akinori
A
D018663:Adrenergic Agents; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D039481:CD11b Antigen / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002460:Cell Line; D004195:Disease Models, Animal; D004224:Diterpenes / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D045442:Rotarod Performance Test / Q000379:methods; D012399:Rotation; D013378:Substantia Nigra / Q000187:drug effects; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
D018663:Adrenergic Agents; D000447:Aldehydes; D039481:CD11b Antigen; D004224:Diterpenes; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D016708:Synaptophysin; D051844:alpha-Synuclein; C452642:serofendic acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; C027576:4-hydroxy-2-nonenal