Early and progressive deficit of neuronal activity patterns in a model of local amyloid pathology in mouse prefrontal cortex

Abstract : Alzheimer’s Disease (AD) is the most common form of dementia. The condition predominantly affects the cerebral cortex and hippocampus and is characterized by the spread of amyloid plaques and neurofibrillary tangles (NFTs). But soluble amyloid-β (Aβ) oligomers have also been identified to accumulate in the brains of AD patients and correlate with cognitive dysfunction more than the extent of plaque deposition. Here, we developed an adeno-associated viral vector expressing the human mutated amyloid precursor protein (AAV-hAPP). Intracranial injection of the AAV into the prefrontal cortex (PFC) allowed the induction of AD-like deficits in adult mice, thereby modelling human pathology. AAV-hAPP expression caused accumulation of Aβ oligomers, microglial activation, astrocytosis and the gradual formation of amyloid plaques and NFTs. In vivo two-photon imaging revealed an increase in neuronal activity, a dysfunction characteristic of the pathology, already during the accumulation of soluble oligomers. Importantly, we found that Aβ disrupts the synchronous spontaneous activity of neurons in PFC that, as in humans, is characterized by ultraslow fluctuation patterns. Our work allowed us to track brain activity changes during disease progression and provides new insight into the early deficits of synchronous ongoing brain activity, the “default network”, in the presence of Aβ peptide.
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Aging, Superintendent of Documents, U.S. Government Printing Office, 2016, 8 (12), pp.3430-3449. <www.aging-us.com/article/101136>. <10.18632/aging.101136>
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Soumis le : mercredi 9 août 2017 - 16:00:10
Dernière modification le : jeudi 10 août 2017 - 10:32:52

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Fani Koukouli, Marie Rooy, Uwe Maskos. Early and progressive deficit of neuronal activity patterns in a model of local amyloid pathology in mouse prefrontal cortex. Aging, Superintendent of Documents, U.S. Government Printing Office, 2016, 8 (12), pp.3430-3449. <www.aging-us.com/article/101136>. <10.18632/aging.101136>. <hal-01573459>

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