Document Type
Article
Publication Date
1-1-2024
Original Citation
Heuer S,
Keezer K,
Hewes A,
Onos KD,
Graham K,
Howell G,
Bloss E.
Control of hippocampal synaptic plasticity by microglia-dendrite interactions depends on genetic context in mouse models of Alzheimer's disease. Alzheimers Dement. 2024;20(1):601-14.
Keywords
JMG, SS1, Humans, Mice, Animals, Alzheimer Disease, Microglia, Amyloid beta-Protein Precursor, Mice, Transgenic, Mice, Inbred C57BL, Hippocampus, Disease Models, Animal, Neuronal Plasticity, Synapses, Amyloid, Dendrites
JAX Source
Alzheimers Dement. 2024;20(1):601-14.
ISSN
1552-5279
PMID
37753835
DOI
https://doi.org/10.1002/alz.13440
Grant
Diana Davis Spencer Foundation, Grant/Award Numbers: AG079877, AG055104; Precision Genetics of Aging, Alzheimer’s Disease and Related Dementias at The Jackson Laboratory, Grant/Award Number: AG062409
Abstract
INTRODUCTION: Human data suggest susceptibility and resilience to features of Alzheimer's disease (AD) such as microglia activation and synaptic dysfunction are under genetic control. However, causal relationships between these processes, and how genomic diversity modulates them remain systemically underexplored in mouse models.
METHODS: AD-vulnerable hippocampal neurons were virally labeled in inbred (C57BL/6J) and wild-derived (PWK/PhJ) APP/PS1 and wild-type mice, and brain microglia depleted from 4 to 8 months of age. Dendrites were assessed for synapse plasticity changes by evaluating spine densities and morphologies.
RESULTS: In C57BL/6J, microglia depletion blocked amyloid-induced synaptic density and morphology changes. At a finer scale, synaptic morphology on individual branches was dependent on microglia-dendrite physical interactions. Conversely, synapses from PWK/PhJ mice showed remarkable stability in response to amyloid, and no evidence of microglia contact-dependent changes on dendrites.
DISCUSSION: These results demonstrate that microglia-dependent synaptic alterations in specific AD-vulnerable projection pathways are differentially controlled by genetic context.
Comments
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.