title: In vivo alterations in calcium buffering capacity in transgenic mouse model of synucleinopathy.
abstract: Abnormal accumulation of α-synuclein is centrally involved in the pathogenesis of many disorders with Parkinsonism and dementia. Previous in vitro studies suggest that α-synuclein dysregulates intracellular calcium. However, it is unclear whether these alterations occur in vivo. For this reason, we investigated calcium dynamics in transgenic mice expressing human WT α-synuclein using two-photon microscopy. We imaged spontaneous and stimulus-induced neuronal activity in the barrel cortex. Transgenic mice exhibited augmented, long-lasting calcium transients characterized by considerable deviation from the exponential decay. The most evident pathology was observed in response to a repetitive stimulation in which subsequent stimuli were presented before relaxation of calcium signal to the baseline. These alterations were detected in the absence of significant increase in neuronal spiking response compared with age-matched controls, supporting the possibility that α-synuclein promoted alterations in calcium dynamics via interference with intracellular buffering mechanisms. The characteristic shape of calcium decay and augmented response during repetitive stimulation can serve as in vivo imaging biomarkers in this model of neurodegeneration, to monitor progression of the disease and screen candidate treatment strategies.
authors: Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA. lydia.reznichenko@gmail.com
authors: Lidia
authors: L
authors: Reznichenko
authors: Qun
authors: Q
authors: Cheng
authors: Krystal
authors: K
authors: Nizar
authors: Sergey L
authors: SL
authors: Gratiy
authors: Payam A
authors: PA
authors: Saisan
authors: Edward M
authors: EM
authors: Rockenstein
authors: Tanya
authors: T
authors: González
authors: Christina
authors: C
authors: Patrick
authors: Brian
authors: B
authors: Spencer
authors: Paula
authors: P
authors: Desplats
authors: Anders M
authors: AM
authors: Dale
authors: Anna
authors: A
authors: Devor
authors: Eliezer
authors: E
authors: Masliah
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001927:Brain Diseases / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein; D002118:Calcium