Hypertrophy of nigral neurons in Torsin1A deletion (DYT1) carriers manifesting dystonia
| Autor: | Hui Peng, Roger Kurlan, Marcie Rabin, Diego Iacono, Maria Geraci-Erck |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Heterozygote Neurite Dystonia Musculorum Deformans Substantia nigra Stereology Biology Muscle hypertrophy 03 medical and health sciences symbols.namesake 0302 clinical medicine medicine Humans Aged Dystonia Aged 80 and over Neurons Dopaminergic Hypertrophy Middle Aged medicine.disease Pathophysiology Substantia Nigra 030104 developmental biology nervous system Neurology Dystonic Disorders Nissl body symbols Female Neurology (clinical) Geriatrics and Gerontology 030217 neurology & neurosurgery Molecular Chaperones |
| Zdroj: | Parkinsonismrelated disorders. 58 |
| ISSN: | 1873-5126 |
| Popis: | To individuate morphometric changes and prevalent types of intraneuronal inclusions in nigral neurons of DYT1 dystonia autopsy-brains.Using precise methods of quantification, such as unbiased stereology, we measured cellular and subcellular volumes of neuromelanin-containing (pigmented) neurons in the substantia nigra (SN) of DYT1 carriers with and without manifestation of generalized dystonia (manif-DYT1 and non-manif-DYT1, respectively), non-DYT1 carriers manifesting generalized dystonia (manif-non-DYT1) patients, and age-matched control subjects (controls). A total of four DYT1 carriers (two manif-DYT1 and two non-manif-DYT1), six manif-non-DYT1 carriers, and six controls autopsy-brains were available for these neuropathological-morphometric analyses. The search of brain lesions was performed for: tau neurofibrillary tangles and neurites, extracellular β-amyloid deposits, Lewy bodies and neurites, TorsinA, Laminin A + C, Ubiquitin, p62, pTDP43 intraneuronal inclusions; and Negri, Bunina, Hirano, Marinesco, Nissl, and Buscaino bodies.An increased mean cell body, nuclear, and nucleolar volume of nigral neurons in manif-DYT1 vs. non-manif-DYT1 (p 0.0001), manif-non-DYT1 (p 0.0001), and controls (p 0.00001) was found. Increased nuclear and nucleolar volumes in manif-non-DYT1 vs. controls were also found. None of the considered possible intraneuronal lesions were more frequent or prevalent in nigral neurons of manif-DYT1 vs. all the other groups.Unbiased stereology-based measurements of nigral neurons enlargement in manif-DYT1 in the absence of intraneuronal inclusions or neurodegenerative processes, is novel. These findings suggest distinct pathogenetic mechanisms between manif-DYT1 vs. non-manif-DYT1 and manif-non-DYT1 dystonia, especially in terms of possible nigral dopaminergic abnormalities. These data could open new pathophysiologic views on specific dopamino-associated pathomechanisms related to the clinical manifestation of generalized dystonia. |
| Databáze: | OpenAIRE |
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