title: Serofendic acid prevents 6-hydroxydopamine-induced nigral neurodegeneration and drug-induced rotational asymmetry in hemi-parkinsonian rats.
abstract: 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.
authors.affiliation: Department of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Kyoto, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inden
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Kondo
authors.forename: Kousuke
authors.initials: K
authors.lastname: Hayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yanagida
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Takata
authors.forename: Daiju
authors.initials: D
authors.lastname: Tsuchiya
authors.forename: Daijiro
authors.initials: D
authors.lastname: Yanagisawa
authors.forename: Kaneyasu
authors.initials: K
authors.lastname: Nishimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
authors.forename: Hachiro
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Akinori
authors.initials: A
authors.lastname: Akaike
mesh_terms: 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
chemical_list: 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