Tissue Clearing and Expansion Methods for Imaging Brain Pathology in Neurodegeneration : From Circuits to Synapses and Beyond
Parra-Damas, Arnaldo (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Saura Antolín, Carlos (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Fecha:	2020
Resumen:	Studying the structural alterations occurring during diseases of the nervous system requires imaging heterogeneous cell populations at the circuit, cellular and subcellular levels. Recent advancements in brain tissue clearing and expansion methods allow unprecedented detailed imaging of the nervous system through its entire scale, from circuits to synapses, including neurovascular and brain lymphatics elements. Here, we review the state-of-the-art of brain tissue clearing and expansion methods, mentioning their main advantages and limitations, and suggest their parallel implementation for circuits-to-synapses brain imaging using conventional (diffraction-limited) light microscopy -such as confocal, two-photon and light-sheet microscopy- to interrogate the cellular and molecular basis of neurodegenerative diseases. We discuss recent studies in which clearing and expansion methods have been successfully applied to study neuropathological processes in mouse models and postmortem human brain tissue. Volumetric imaging of cleared intact mouse brains and large human brain samples has allowed unbiased assessment of neuropathological hallmarks. In contrast, nanoscale imaging of expanded cells and brain tissue has been used to study the effect of protein aggregates on specific subcellular structures. Therefore, these approaches can be readily applied to study a wide range of brain processes and pathological mechanisms with cellular and subcellular resolution in a time- and cost-efficient manner. We consider that a broader implementation of these technologies is necessary to reveal the full landscape of cellular and molecular mechanisms underlying neurodegenerative diseases.
Ayudas:	Ministerio de Ciencia e Innovación SAF2016-80027-R Ministerio de Ciencia e Innovación PID2019-106615RB-100 Ministerio de Sanidad y Consumo CB06/05/0042
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Tissue clearing ; Expansion microscopy ; Neuropathology ; Neurodegeneration ; Super-resolution microscopy
Publicado en:	Frontiers in Neuroscience, Vol. 14 (october 2020) , ISSN 1662-453X

DOI: 10.3389/fnins.2020.00914
PMID: 33122983

12 p, 2.1 MB

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