Alpha-synuclein aggregates are excluded from calbindin-D28k-positive neurons in dementia with Lewy bodies and a unilateral rotenone mouse model
| Autor: | Dean Louis Pountney, Alexandre N. Rcom-H'cheo-Gauthier, Adrian Cuda Banda Meedeniya, Amelia Davis |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Lewy Body Disease medicine.medical_specialty Parkinson's disease Biology Immunofluorescence medicine.disease_cause Lesion 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Mice Protein Aggregates 0302 clinical medicine Internal medicine Rotenone medicine Animals Humans Molecular Biology Aged Alpha-synuclein Aged 80 and over Neurons medicine.diagnostic_test Dementia with Lewy bodies Neurodegeneration Cell Biology medicine.disease nervous system diseases Mice Inbred C57BL Oxidative Stress 030104 developmental biology Endocrinology nervous system chemistry Calbindin 1 alpha-Synuclein medicine.symptom Neuroscience 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Molecular and cellular neurosciences. 77 |
| ISSN: | 1095-9327 |
| Popis: | α-Synuclein (α-syn) aggregates (Lewy bodies) in Dementia with Lewy Bodies (DLB) may be associated with disturbed calcium homeostasis and oxidative stress. We investigated the interplay between α-syn aggregation, expression of the calbindin-D28k (CB) neuronal calcium-buffering protein and oxidative stress, combining immunofluorescence double labelling and Western analysis, and examining DLB and normal human cases and a unilateral oxidative stress lesion model of α-syn disease (rotenone mouse). DLB cases showed a greater proportion of CB+ cells in affected brain regions compared to normal cases with Lewy bodies largely present in CB- neurons and virtually undetected in CB+ neurons. The unilateral rotenone-lesioned mouse model showed a greater proportion of CB+ cells and α-syn aggregates within the lesioned hemisphere than the control hemisphere, especially proximal to the lesion site, and α-syn inclusions occurred primarily in CB- cells and were almost completely absent in CB+ cells. Consistent with the immunofluorescence data, Western analysis showed the total CB level was 25% higher in lesioned compared to control hemisphere in aged animals that are more sensitive to lesion and 20% higher in aged compared to young mice in lesioned hemisphere, but not significantly different between young and aged in the control hemisphere. Taken together, the findings show α-syn aggregation is excluded from CB+ neurons, although the increased sensitivity of aged animals to lesion was not related to differential CB expression. |
| Databáze: | OpenAIRE |
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