RRC ID 81845
Author Sauerbeck AD, Gangolli M, Reitz SJ, Salyards MH, Kim SH, Hemingway C, Gratuze M, Makkapati T, Kerschensteiner M, Holtzman DM, Brody DL, Kummer TT.
Title SEQUIN Multiscale Imaging of Mammalian Central Synapses Reveals Loss of Synaptic Connectivity Resulting from Diffuse Traumatic Brain Injury.
Journal Neuron
Abstract The brain's complex microconnectivity underlies its computational abilities and vulnerability to injury and disease. It has been challenging to illuminate the features of this synaptic network due to the small size and dense packing of its elements. Here, we describe a rapid, accessible super-resolution imaging and analysis workflow-SEQUIN-that quantifies central synapses in human tissue and animal models, characterizes their nanostructural and molecular features, and enables volumetric imaging of mesoscale synaptic networks without the production of large histological arrays. Using SEQUIN, we identify cortical synapse loss resulting from diffuse traumatic brain injury, a highly prevalent connectional disorder. Similar synapse loss is observed in three murine models of Alzheimer-related neurodegeneration, where SEQUIN mesoscale mapping identifies regional synaptic vulnerability. These results establish an easily implemented and robust nano-to-mesoscale synapse quantification and characterization method. They furthermore identify a shared mechanism-synaptopathy-between Alzheimer neurodegeneration and its best-established epigenetic risk factor, brain trauma.
Volume 107(2)
Pages 257-273.e5
Published 2020-7-22
DOI 10.1016/j.neuron.2020.04.012
PII S0896-6273(20)30281-6
PMID 32392471
PMC PMC7381374
MeSH Animals Brain Injuries, Traumatic / pathology* Brain Mapping Central Nervous System / diagnostic imaging* Central Nervous System / ultrastructure Cerebral Cortex / pathology Humans Mammals Mice Nanostructures / ultrastructure* Neural Pathways / diagnostic imaging* Neural Pathways / ultrastructure* Neuroimaging / methods* Synapses / ultrastructure*
Resource
Mice RBRC06343