AUTHOR=Nishijima Haruo , Kimura Tamaki , Mori Fumiaki , Wakabayashi Koichi , Kinoshita Iku , Nakamura Takashi , Kon Tomoya , Suzuki Chieko , Tomiyama Masahiko 

TITLE=Effects of Aging on Levo-Dihydroxyphenylalanine- Induced Dyskinesia in a Rat Model of Parkinson’s Disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=13

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.650350

DOI=10.3389/fnagi.2021.650350

ISSN=1663-4365

ABSTRACT=<sec><title>Background</title><p>It remains unclear why patients with young-onset Parkinson’s disease more often develop levo-dihydroxyphenylalanine (<sc>L</sc>-dopa)-induced dyskinesia (LID) and have a more severe form than patients with old-onset Parkinson’s disease. Previous studies using animal models have failed to show young-onset Parkinson’s disease enhances LID.</p></sec><sec><title>Objectives</title><p>To evaluate the association of age at dopaminergic denervation (onset age) and initiation of <sc>L</sc>-dopa treatment (treatment age) with LID development in model rats.</p></sec><sec><title>Methods</title><p>We established rat models of young- and old-lesioned Parkinson’s disease (6-hydroxydopamine lesions at 10 and 88 weeks of age, respectively). Dopaminergic denervation was confirmed by the rotational behavior test using apomorphine. Rats in the young-lesioned group were allocated to either <sc>L</sc>-dopa treatment at a young or old age, or saline treatment. Rats in the old-lesioned group were allocated to either <sc>L</sc>-dopa treatment or saline group. We evaluated <sc>L</sc>-dopa-induced abnormal involuntary movements during the 14-day treatment period. We also examined preprodynorphin mRNA expression in the striatum (a neurochemical hallmark of LID) and the volume of the medial globus pallidus (a pathological hallmark of LID).</p></sec><sec><title>Results</title><p>LID-like behavior was enhanced in <sc>L</sc>-dopa-treated young-lesioned rats compared with <sc>L</sc>-dopa-treated old-lesioned rats. Preprodynorphin mRNA expression was higher in <sc>L</sc>-dopa-treated young-lesioned rats than in in <sc>L</sc>-dopa-treated old-lesioned rats. The volume of the medial globus pallidus was greater in <sc>L</sc>-dopa-treated young-lesioned rats than in <sc>L</sc>-dopa-treated old-lesioned rats. Treatment age did not affect LID-like behavior or the degree of medial globus pallidus hypertrophy in the young-lesioned model.</p></sec><sec><title>Conclusion</title><p>Both dopaminergic denervation and <sc>L</sc>-dopa initiation at a young age contributed to the development of LID; however, the former may be a more important factor.</p></sec>