Relationship Among α-Synuclein Accumulation, Dopamine Synthesis, and Neurodegeneration in Parkinson Disease Substantia Nigra
| Autor: | Makoto Yoshimoto, Koichi Wakabayashi, Makoto Nishie, Akiyoshi Kakita, Fumiaki Mori, Hitoshi Takahashi |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Tyrosine 3-Monooxygenase Cell Survival Dopamine Down-Regulation Substantia nigra Biology Pathology and Forensic Medicine Cellular and Molecular Neuroscience chemistry.chemical_compound Neuromelanin Internal medicine medicine Humans Aged Aged 80 and over Inclusion Bodies Neurons Alpha-synuclein Cell Death Tyrosine hydroxylase Neurodegeneration Locus Ceruleus Parkinson Disease General Medicine Middle Aged medicine.disease Immunohistochemistry Substantia Nigra medicine.anatomical_structure Endocrinology nervous system Neurology chemistry Cytoprotection Nerve Degeneration alpha-Synuclein Locus Coeruleus Neurology (clinical) Neuron medicine.drug |
| Zdroj: | Journal of Neuropathology & Experimental Neurology. 65:808-815 |
| ISSN: | 1554-6578 0022-3069 |
| DOI: | 10.1097/01.jnen.0000230520.47768.1a |
| Popis: | The histologic hallmark of Parkinson disease (PD) is loss of pigmented neurons in the substantia nigra (SN) and locus ceruleus (LC) with accumulation of alpha-synuclein (alphaS). It has been reported that tyrosine hydroxylase (TH)-negative pigmented neurons are present in these nuclei of patients with PD. However, the relationship between TH immunoreactivity and alphaS accumulation remains uncertain. We immunohistochemically examined the SN and LC from patients with PD (n = 10) and control subjects (n = 7). A correlation study indicated a close relationship among decreased TH immunoreactivity, alphaS accumulation, and neuronal loss. In addition, 10% of pigmented neurons in the SN and 54.9% of those in the LC contained abnormal alphaS aggregates. Moreover, 82.3% of pigmented neurons bearing alphaS aggregates in the SN and 39.2% of those in the LC lacked TH immunoreactivity, suggesting that pigmented neurons in the SN have a greater tendency to lack TH activity than those in the LC. Recent studies have shown that this decrease of TH activity leads to a decrease of cytotoxic substances and that decreased dopamine synthesis leads to a reduction of cytotoxic alphaS oligomers. Therefore, the decrease of TH immunoreactivity in pigmented neurons demonstrated here can be considered to represent a cytoprotective mechanism in PD. |
| Databáze: | OpenAIRE |
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