Tau- but not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models
Many mouse models of Alzheimer’s disease (AD) exhibit impairments in hippocampal long-term-potentiation (LTP), seemingly corroborating the strong correlation between synaptic loss and cognitive decline reported in human studies. In other AD mouse models LTP is unaffected, but other defects in synaptic plasticity may still be present. We recently reported that THY-Tau22 transgenic mice, that overexpress human Tau protein carrying P301S and G272 V mutations and show normal LTP upon high-frequency-stimulation (HFS), develop severe changes in NMDAR mediated long-term-depression (LTD), the physiological counterpart of LTP. In the present study, we focused on putative effects of AD-related pathologies on depotentiation (DP), another form of synaptic plasticity. Using a novel protocol to induce DP in the CA1-region, we found in 11–15 months old male THY-Tau22 and APPPS1–21 transgenic mice that DP was not deteriorated by Aß pathology while significantly compromised by Tau pathology. Our findings advocate DP as a complementary form of synaptic plasticity that may help in elucidating synaptic pathomechanisms associated with different types of dementia.
Other Information
Published in: Acta Neuropathologica Communications
License: http://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.1186/s40478-019-0813-4
Funding
Open Access funding provided by the Qatar National Library.
History
Language
- English
Publisher
Springer NaturePublication Year
- 2019
License statement
This Item is licensed under the Creative Commons Attribution 4.0 International License.Institution affiliated with
- Hamad Bin Khalifa University
- Qatar Biomedical Research Institute - HBKU