title: Behavioral correlates of transneuronal degeneration of substantia nigra reticulata neurons are reversed by ablation of the subthalamic nucleus.
abstract: In rats, acute injury of neurons in the caudate nucleus (CN) and globus pallidus (GP) by local injection of ibotenic acid (IA) or by transient forebrain ischemia has caused transneuronal cell death of neurons in the substantia nigra reticulata (SNr) weeks after the initial injury. Recently transient expression of an immediate early gene c-fos was induced specifically in neurons of the subthalamic nucleus (STN) and SNr at 36-48 h after the IA-lesions, prior to the delayed degeneration of SNr neurons. These cellular and molecular events may alter the level of inhibitory output from the basal ganglia and lead to movement disorders. To test (i) whether movement disorders occur in the early period after unilateral lesions of the CN and GP by IA-injection, and (ii) whether ablation of the STN reverses the early movement disorders, we used a modified version of Porsolt forced swim test in which the lesion-induced asymmetry of motor function becomes apparent as rotation when the animals are forced to swim. Following unilateral IA-lesions of the right CN and GP in rats, rapid contraversive rotation appeared transiently 36-48 h after the lesions, and, in turn, slow ipsiversive rotation appeared at 3-5 days postlesion. Prior ablation of the ipsilateral STN reversed these early movement disorders produced by the unilateral IA-lesions of the CN and GP and instead created persistent contraversive rotation 7-10 days after the lesions. Each phase of the dominant rotation behavior was dependent on asymmetrical limb motor activity; decreased left limb activity caused contraversive rotation, and increased left limb activity caused ipsiversive rotation. Reversal of these early movement disorders suggests that ablation of the STN prevents the transneuronal degeneration of the SNr.
authors.affiliation: Department of Neurobiology, Tottori University School of Medicine, Yonago, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Saji
authors.forename: Y
authors.initials: Y
authors.lastname: Endo
authors.forename: T
authors.initials: T
authors.lastname: Miyanishi
authors.forename: B T
authors.initials: BT
authors.lastname: Volpe
authors.forename: K
authors.initials: K
authors.lastname: Ohno
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D005917:Globus Pallidus / Q000166:cytology / Q000502:physiology; D007051:Ibotenic Acid / Q000633:toxicity; D008297:Male; D009069:Movement Disorders / Q000523:psychology; D009410:Nerve Degeneration / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013550:Swimming; D013787:Thalamic Nuclei / Q000166:cytology / Q000502:physiology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D007051:Ibotenic Acid