title: A rat model of striatonigral degeneration generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum.
abstract: A double toxin-double lesion strategy is well-known to generate a rat model of striatonigral degeneration (SND) such as multiple system atrophy-parkinsonian type. However, with this model it is difficult to distinguish SND from Parkinson's disease (PD). In this study, we propose a new rat model of SND, which is generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum. Stepping tests performed 30 min after intraperitoneal L-dopa administration at 6 weeks post-surgery revealed an L-dopa response in the PD group but not the SND group. Apomorphine-induced rotation tests revealed no rotational bias in the SND group, which persisted for 2 months, but contralateral rotations in the PD group. MicroPET scans revealed glucose hypometabolism and dopamine transporter impairment on the lesioned striatum in the SND group. Tyrosine hydroxylase immunostaining in the SND group revealed that 74.7% of nigral cells on the lesioned side were lost after lesion surgery. These results suggest that the proposed simultaneous double toxin-double lesion method successfully created a rat model of SND that had behavioral outcomes, multitracer microPET evaluation, and histological aspects consistent with SND pathology. This model will be useful for future study of SND.
authors.affiliation: Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hyung Ho
authors.identifier: 0000-0003-4123-0112
authors.initials: HH
authors.lastname: Yoon
authors.affiliation: Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Yong Hwan
authors.identifier: 0000-0003-3308-0177
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Eun Sil
authors.identifier: 0000-0003-0064-5653
authors.initials: ES
authors.lastname: Shin
authors.affiliation: Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sang Ryong
authors.identifier: 0000-0002-8340-7978
authors.initials: SR
authors.lastname: Jeon
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D020955:Striatonigral Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D014110:Touch / Q000187:drug effects
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D007980:Levodopa; D016627:Oxidopamine; D017378:Quinolinic Acid; D005947:Glucose; D001058:Apomorphine
keywords: FP-CIT; L-dopa Response; Multiple System Atrophy; Positron Emission Tomography; Simultaneous Injection; Striatonigral Degeneration