Aβ Plaques Lead to Aberrant Regulation of Calcium Homeostasis In Vivo Resulting in Structural and Functional Disruption of Neuronal Networks
| Autor: | Brian J. Bacskai, Bradley T. Hyman, Carli R. Lattarulo, Hai Yan Wu, Kishore V. Kuchibhotla, Samuel T. Goldman |
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| Rok vydání: | 2008 |
| Předmět: |
Genetically modified mouse
Neuroscience(all) HUMDISEASE chemistry.chemical_element Mice Transgenic Plaque Amyloid CHO Cells Calcium Biology Article MOLNEURO Mice Cricetulus In vivo Alzheimer Disease Cricetinae medicine Animals Homeostasis Humans Senile plaques Cells Cultured Calcium metabolism Neurons Amyloid beta-Peptides General Neuroscience Brain Compartmentalization (psychology) medicine.disease Cell biology chemistry SIGNALING Alzheimer's disease Nerve Net Neuroscience Chickens |
| Zdroj: | Neuron. 59(2):214-225 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2008.06.008 |
| Popis: | Alzheimer's disease is characterized by the deposition of senile plaques and progressive dementia. The molecular mechanisms that couple plaque deposition to neural system failure, however, are unknown. Using transgenic mouse models of AD together with multiphoton imaging, we measured neuronal calcium in individual neurites and spines in vivo using the genetically encoded calcium indicator Yellow Cameleon 3.6. Quantitative imaging revealed elevated [Ca(2+)]i (calcium overload) in approximately 20% of neurites in APP mice with cortical plaques, compared to less than 5% in wild-type mice, PS1 mutant mice, or young APP mice (animals without cortical plaques). Calcium overload depended on the existence and proximity to plaques. The downstream consequences included the loss of spinodendritic calcium compartmentalization (critical for synaptic integration) and a distortion of neuritic morphologies mediated, in part, by the phosphatase calcineurin. Together, these data demonstrate that senile plaques impair neuritic calcium homeostasis in vivo and result in the structural and functional disruption of neuronal networks. |
| Databáze: | OpenAIRE |
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