Serofendic acid prevents 6-hydroxydopamine-induced nigral neurodegeneration and drug-induced rotational asymmetry in hemi-parkinsonian rats

Masatoshi Inden, Yoshihisa Kitamura, Jun-Ichi Kondo, Kousuke Hayashi, Takashi Yanagida, Kazuyuki Takata, Daiju Tsuchiya, Daijiro Yanagisawa, Kaneyasu Nishimura, Takashi Taniguchi, Shun Shimohama, Hachiro Sugimoto, Akinori Akaike
Journal of Neurochemistry 2005, 95 (4): 950-61
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.

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