Pedunculopontine Nucleus Cholinergic Deficiency in Cervical Dystonia
Autor: | Edson Amaro, Mark Hallett, Eduardo Joaquim Lopes Alho, D Iacono, Nancy A. Edwards, Demelio Urbano, Ana Tereza Di Lorenzo Alho, Abhik Ray-Chaudhury, Karin Mente, Silvina G. Horovitz |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Dystonia Pathology medicine.medical_specialty business.industry Putamen Striatum medicine.disease Choline acetyltransferase nervous system diseases 03 medical and health sciences 030104 developmental biology 0302 clinical medicine nervous system Neurology medicine Cholinergic Neurology (clinical) Cervical dystonia Cholinergic neuron business 030217 neurology & neurosurgery Pedunculopontine nucleus |
Zdroj: | Movement Disorders. 33:827-834 |
ISSN: | 0885-3185 |
DOI: | 10.1002/mds.27358 |
Popis: | Background The etiology of cervical dystonia is unknown. Cholinergic abnormalities have been identified in dystonia animal models and human imaging studies. Some animal models have cholinergic neuronal loss in the striatum and increased acetylcholinesterase activity in the pedunculopontine nucleus. Objectives The objective of this study was to determine the presence of cholinergic abnormalities in the putamen and pedunculopontine nucleus in cervical dystonia human brain donors. Methods Formalin-fixed brain tissues were obtained from 8 cervical dystonia and 7 age-matched control brains (controls). Pedunculopontine nucleus was available in only 6 cervical dystonia and 5 controls. Neurodegeneration was evaluated pathologically in the putamen, pedunculopontine nucleus, and other regions. Cholinergic neurons were detected using choline acetyltransferase immunohistochemistry in the putamen and pedunculopontine nucleus. Putaminal cholinergic neurons were quantified. A total of 6 cervical dystonia patients and 6 age-matched healthy controls underwent diffusion tensor imaging to determine if there were white matter microstructural abnormalities around the pedunculopontine nucleus. Results Decreased or absent choline acetyltransferase staining was identified in all 6 pedunculopontine nucleus samples in cervical dystonia. In contrast, strong choline acetyltransferase staining was present in 4 of 5 pedunculopontine nucleus controls. There were no differences in pedunculopontine nucleus diffusion tensor imaging between cervical dystonia and healthy controls. There was no difference in numbers of putaminal cholinergic neurons between cervical dystonia and controls. Conclusions Our findings suggest that pedunculopontine nucleus choline acetyltransferase deficiency represents a functional cholinergic deficit in cervical dystonia. Structural lesions and confounding neurodegenerative processes were excluded by absence of neuronal loss, gliosis, diffusion tensor imaging abnormalities, and beta-amyloid, tau, and alpha-synuclein pathologies. © 2018 International Parkinson and Movement Disorder Society. |
Databáze: | OpenAIRE |
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