Dystonia-like behaviors and impaired sensory–motor integration following neurotoxic lesion of the pedunculopontine tegmental nucleus in mice
IntroductionThe pedunculopontine nucleus (PPTg) is a vital interface between the basal ganglia and cerebellum, participating in modulation of the locomotion and muscle tone. Pathological changes of the PPTg have been reported in patients and animal models of dystonia, while its effect and mechanism...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1102837/full |
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| author | Jun-Hui Su Jun-Hui Su Yao-Wen Hu Yun-Ping Song Yi Yang Ruo-Yu Li Kai-Ge Zhou Ling Hu Xin-Hua Wan Fei Teng Ling-Jing Jin |
| author_facet | Jun-Hui Su Jun-Hui Su Yao-Wen Hu Yun-Ping Song Yi Yang Ruo-Yu Li Kai-Ge Zhou Ling Hu Xin-Hua Wan Fei Teng Ling-Jing Jin |
| author_sort | Jun-Hui Su |
| collection | DOAJ |
| description | IntroductionThe pedunculopontine nucleus (PPTg) is a vital interface between the basal ganglia and cerebellum, participating in modulation of the locomotion and muscle tone. Pathological changes of the PPTg have been reported in patients and animal models of dystonia, while its effect and mechanism on the phenotyping of dystonia is still unknown.MethodsIn this study, a series of behavioral tests focusing on the specific deficits of dystonia were conducted for mice with bilateral and unilateral PPTg excitotoxic lesion, including the dystonia-like movements evaluation, different types of sensory-motor integrations, explorative behaviors and gait. In addition, neural dysfunctions including apoptosis, neuroinflammation, neurodegeneration and neural activation of PPTg-related motor areas in the basal ganglia, reticular formations and cerebellum were also explored.ResultsBoth bilateral and unilateral lesion of the PPTg elicited dystonia-like behaviors featured by the hyperactivity of the hindlimb flexors. Moreover, proprioceptive and auditory sensory-motor integrations were impaired in bilaterally lesioned mice, while no overt alterations were found for the tactile sensory-motor integration, explorative behaviors and gait. Similar but milder behavioral deficits were found in the unilaterally lesioned mice, with an effective compensation was observed for the auditory sensory-motor integration. Histologically, no neural loss, apoptosis, neuroinflammation and neurodegeneration were found in the substantia nigra pars compacta and caudate putamen (CPu) following PPTg lesion, while reduced neural activity was found in the dorsolateral part of the CPu and striatal indirect pathway-related structures including subthalamic nucleus, globus pallidus internus and substantia nigra pars reticular. Moreover, the neural activity was decreased for the reticular formations such as pontine reticular nucleus, parvicellular reticular nucleus and gigantocellular reticular nucleus, while deep cerebellar nuclei were spared.ConclusionIn conclusion, lesion of the PPTg could elicit dystonia-like behaviors through its effect on the balance of the striatal pathways and the reticular formations. |
| first_indexed | 2024-04-09T20:37:54Z |
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| id | doaj.art-6069f7aa6fdd4d19bb7b86a66e4567a3 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-09T20:37:54Z |
| publishDate | 2023-03-01 |
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| series | Frontiers in Neurology |
| spelling | doaj.art-6069f7aa6fdd4d19bb7b86a66e4567a32023-03-30T06:25:55ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-03-011410.3389/fneur.2023.11028371102837Dystonia-like behaviors and impaired sensory–motor integration following neurotoxic lesion of the pedunculopontine tegmental nucleus in miceJun-Hui Su0Jun-Hui Su1Yao-Wen Hu2Yun-Ping Song3Yi Yang4Ruo-Yu Li5Kai-Ge Zhou6Ling Hu7Xin-Hua Wan8Fei Teng9Ling-Jing Jin10Department of Neurology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology and Neurological Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology and Neurological Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Laboratory Animal Science, Fudan University, Shanghai, ChinaDepartment of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Neurology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology and Neurological Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, ChinaIntroductionThe pedunculopontine nucleus (PPTg) is a vital interface between the basal ganglia and cerebellum, participating in modulation of the locomotion and muscle tone. Pathological changes of the PPTg have been reported in patients and animal models of dystonia, while its effect and mechanism on the phenotyping of dystonia is still unknown.MethodsIn this study, a series of behavioral tests focusing on the specific deficits of dystonia were conducted for mice with bilateral and unilateral PPTg excitotoxic lesion, including the dystonia-like movements evaluation, different types of sensory-motor integrations, explorative behaviors and gait. In addition, neural dysfunctions including apoptosis, neuroinflammation, neurodegeneration and neural activation of PPTg-related motor areas in the basal ganglia, reticular formations and cerebellum were also explored.ResultsBoth bilateral and unilateral lesion of the PPTg elicited dystonia-like behaviors featured by the hyperactivity of the hindlimb flexors. Moreover, proprioceptive and auditory sensory-motor integrations were impaired in bilaterally lesioned mice, while no overt alterations were found for the tactile sensory-motor integration, explorative behaviors and gait. Similar but milder behavioral deficits were found in the unilaterally lesioned mice, with an effective compensation was observed for the auditory sensory-motor integration. Histologically, no neural loss, apoptosis, neuroinflammation and neurodegeneration were found in the substantia nigra pars compacta and caudate putamen (CPu) following PPTg lesion, while reduced neural activity was found in the dorsolateral part of the CPu and striatal indirect pathway-related structures including subthalamic nucleus, globus pallidus internus and substantia nigra pars reticular. Moreover, the neural activity was decreased for the reticular formations such as pontine reticular nucleus, parvicellular reticular nucleus and gigantocellular reticular nucleus, while deep cerebellar nuclei were spared.ConclusionIn conclusion, lesion of the PPTg could elicit dystonia-like behaviors through its effect on the balance of the striatal pathways and the reticular formations.https://www.frontiersin.org/articles/10.3389/fneur.2023.1102837/fullpedunculopontine nucleusdystoniasensory-motor integrationmotor performancereticular formationstriatal pathways |
| spellingShingle | Jun-Hui Su Jun-Hui Su Yao-Wen Hu Yun-Ping Song Yi Yang Ruo-Yu Li Kai-Ge Zhou Ling Hu Xin-Hua Wan Fei Teng Ling-Jing Jin Dystonia-like behaviors and impaired sensory–motor integration following neurotoxic lesion of the pedunculopontine tegmental nucleus in mice Frontiers in Neurology pedunculopontine nucleus dystonia sensory-motor integration motor performance reticular formation striatal pathways |
| title | Dystonia-like behaviors and impaired sensory–motor integration following neurotoxic lesion of the pedunculopontine tegmental nucleus in mice |
| title_full | Dystonia-like behaviors and impaired sensory–motor integration following neurotoxic lesion of the pedunculopontine tegmental nucleus in mice |
| title_fullStr | Dystonia-like behaviors and impaired sensory–motor integration following neurotoxic lesion of the pedunculopontine tegmental nucleus in mice |
| title_full_unstemmed | Dystonia-like behaviors and impaired sensory–motor integration following neurotoxic lesion of the pedunculopontine tegmental nucleus in mice |
| title_short | Dystonia-like behaviors and impaired sensory–motor integration following neurotoxic lesion of the pedunculopontine tegmental nucleus in mice |
| title_sort | dystonia like behaviors and impaired sensory motor integration following neurotoxic lesion of the pedunculopontine tegmental nucleus in mice |
| topic | pedunculopontine nucleus dystonia sensory-motor integration motor performance reticular formation striatal pathways |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1102837/full |
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