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P1‐219: EFFECTS OF TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS) ON BRAIN CORTEX PLASTICITY IN A MOUSE MODEL OF ALZHEIMER'S DISEASE
Author(s) -
Cocco Sara,
Rinaudo Marco,
Barbati Saviana Antonella,
Gironi Katia,
Podda Maria Vittoria,
Grassi Claudio
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.774
Subject(s) - transcranial direct current stimulation , neuroscience , long term potentiation , morris water navigation task , synaptophysin , synaptic plasticity , neuroplasticity , hippocampus , psychology , brain stimulation , stimulation , hippocampal formation , medicine , immunohistochemistry , receptor
damage in situ ligation followed by proximity ligation assay (DIPLA) to differentiate cellular staining patterns that represent DSBs from those caused by other processes. Results: We find increased gammaH2AX-labeled neurons in the hippocampus and frontal cortex ofMCI and AD patients, as compared to age-matched controls. In contrast to the focal pattern associated with DSBs, some neurons and glia in humans and mice showed diffuse pan-nuclear patterns of gammaH2AX, which could be elicited by increasing neuronal activity in mice and primary neuronal cultures. Using the DI-PLA, we show that such activity-induced increases in pan-nuclear gammaH2AX do not indicate the presence of true DSBs. Conclusions: Our study demonstrates that neuronal DSBs accumulate from early stages of AD pathology, raising the possibility that this process causally contributes to cellular dysfunction and cell death in AD. Our finding that pan-nuclear increases in gammaH2AX formation can result from increases in neuronal activity and do not represent DSBs highlight the pitfalls of using total gammaH2AX levels as a proxy for DSBs, and may help resolve some conflicting findings in the literature regarding DSBs in AD. Supported by NIH grants AG011385 and AG053981.