title: Alpha-synuclein aggregates are excluded from calbindin-D28k-positive neurons in dementia with Lewy bodies and a unilateral rotenone mouse model.
abstract: 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.
authors.affiliation: Menzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Alexandre N
authors.initials: AN
authors.lastname: Rcom-H'cheo-Gauthier
authors.affiliation: Menzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Amelia
authors.initials: A
authors.lastname: Davis
authors.affiliation: Menzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Adrian C B
authors.initials: ACB
authors.lastname: Meedeniya
authors.affiliation: Menzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, Australia. Electronic address: d.pountney@griffith.edu.au.
authors.forename: Dean L
authors.initials: DL
authors.lastname: Pountney
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D064092:Calbindin 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020961:Lewy Body Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D066329:Protein Aggregates; D012402:Rotenone / Q000633:toxicity; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D064092:Calbindin 1; D066329:Protein Aggregates; D051844:alpha-Synuclein; D012402:Rotenone
keywords: Alpha-synuclein; Calbindin-D28k; Calcium; Dementia with Lewy Bodies; Neurodegeneration; Oxidative stress; Parkinson's disease