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Mapping Solute Clearance From the Mouse Hippocampus Using a 3D Imaging Cryomicrotome

The hippocampus is susceptible to protein aggregation in neurodegenerative diseases such as Alzheimer’s disease. This protein accumulation is partially attributed to an impaired clearance; however, the removal pathways for fluids and waste products are not fully understood. The aim of this study was...

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Autores principales: Naessens, Daphne M. P., Dobbe, Johannes G. G., de Vos, Judith, VanBavel, Ed, Bakker, Erik N. T. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044999/
https://www.ncbi.nlm.nih.gov/pubmed/33867918
http://dx.doi.org/10.3389/fnins.2021.631325
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author Naessens, Daphne M. P.
Dobbe, Johannes G. G.
de Vos, Judith
VanBavel, Ed
Bakker, Erik N. T. P.
author_facet Naessens, Daphne M. P.
Dobbe, Johannes G. G.
de Vos, Judith
VanBavel, Ed
Bakker, Erik N. T. P.
author_sort Naessens, Daphne M. P.
collection PubMed
description The hippocampus is susceptible to protein aggregation in neurodegenerative diseases such as Alzheimer’s disease. This protein accumulation is partially attributed to an impaired clearance; however, the removal pathways for fluids and waste products are not fully understood. The aim of this study was therefore to map the clearance pathways from the mouse brain. A mixture of two fluorescently labeled tracers with different molecular weights was infused into the hippocampus. A small subset of mice (n = 3) was sacrificed directly after an infusion period of 10 min to determine dispersion of the tracer due to the infusion, while another group was sacrificed after spreading of the tracers for an additional 80 min (n = 7). Upon sacrifice, mice were frozen and sectioned as a whole by the use of a custom-built automated imaging cryomicrotome. Detailed 3D reconstructions were created to map the tracer spreading. We observed that tracers distributed over the hippocampus and entered adjacent brain structures, such as the cortex and cerebroventricular system. An important clearance pathway was found along the ventral part of the hippocampus and its bordering interpeduncular cistern. From there, tracers left the brain via the subarachnoid spaces in the directions of both the nose and the spinal cord. Although both tracers followed the same route, the small tracer distributed further, implying a major role for diffusion in addition to convection. Taken together, these results reveal an important clearance pathway of solutes from the hippocampus.
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spelling pubmed-80449992021-04-15 Mapping Solute Clearance From the Mouse Hippocampus Using a 3D Imaging Cryomicrotome Naessens, Daphne M. P. Dobbe, Johannes G. G. de Vos, Judith VanBavel, Ed Bakker, Erik N. T. P. Front Neurosci Neuroscience The hippocampus is susceptible to protein aggregation in neurodegenerative diseases such as Alzheimer’s disease. This protein accumulation is partially attributed to an impaired clearance; however, the removal pathways for fluids and waste products are not fully understood. The aim of this study was therefore to map the clearance pathways from the mouse brain. A mixture of two fluorescently labeled tracers with different molecular weights was infused into the hippocampus. A small subset of mice (n = 3) was sacrificed directly after an infusion period of 10 min to determine dispersion of the tracer due to the infusion, while another group was sacrificed after spreading of the tracers for an additional 80 min (n = 7). Upon sacrifice, mice were frozen and sectioned as a whole by the use of a custom-built automated imaging cryomicrotome. Detailed 3D reconstructions were created to map the tracer spreading. We observed that tracers distributed over the hippocampus and entered adjacent brain structures, such as the cortex and cerebroventricular system. An important clearance pathway was found along the ventral part of the hippocampus and its bordering interpeduncular cistern. From there, tracers left the brain via the subarachnoid spaces in the directions of both the nose and the spinal cord. Although both tracers followed the same route, the small tracer distributed further, implying a major role for diffusion in addition to convection. Taken together, these results reveal an important clearance pathway of solutes from the hippocampus. Frontiers Media S.A. 2021-03-22 /pmc/articles/PMC8044999/ /pubmed/33867918 http://dx.doi.org/10.3389/fnins.2021.631325 Text en Copyright © 2021 Naessens, Dobbe, de Vos, VanBavel and Bakker. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Naessens, Daphne M. P.
Dobbe, Johannes G. G.
de Vos, Judith
VanBavel, Ed
Bakker, Erik N. T. P.
Mapping Solute Clearance From the Mouse Hippocampus Using a 3D Imaging Cryomicrotome
title Mapping Solute Clearance From the Mouse Hippocampus Using a 3D Imaging Cryomicrotome
title_full Mapping Solute Clearance From the Mouse Hippocampus Using a 3D Imaging Cryomicrotome
title_fullStr Mapping Solute Clearance From the Mouse Hippocampus Using a 3D Imaging Cryomicrotome
title_full_unstemmed Mapping Solute Clearance From the Mouse Hippocampus Using a 3D Imaging Cryomicrotome
title_short Mapping Solute Clearance From the Mouse Hippocampus Using a 3D Imaging Cryomicrotome
title_sort mapping solute clearance from the mouse hippocampus using a 3d imaging cryomicrotome
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044999/
https://www.ncbi.nlm.nih.gov/pubmed/33867918
http://dx.doi.org/10.3389/fnins.2021.631325
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