Nizari, Shereen;
Carare, Roxana O;
Romero, Ignacio A;
Hawkes, Cheryl A;
(2019)
3D Reconstruction of the Neurovascular Unit Reveals Differential Loss of Cholinergic Innervation in the Cortex and Hippocampus of the Adult Mouse Brain.
Frontiers in Aging Neuroscience
, 11
, Article 172. 10.3389/fnagi.2019.00172.
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Abstract
Increasing evidence supports a role for cerebrovasculature dysfunction in the etiology of Alzheimer’s disease (AD). Blood vessels in the brain are composed of a collection of cells and acellular material that comprise the neurovascular unit (NVU). The NVU in the hippocampus and cortex receives innervation from cholinergic neurons that originate in the basal forebrain. Death of these neurons and their nerve fibers is an early feature of AD. However, the effect of the loss of cholinergic innervation on the NVU is not well characterized. The purpose of this study was to evaluate the effect of the loss of cholinergic innervation of components of the NVU at capillaries, arteries and veins in the hippocampus and cortex. Adult male C57BL/6 mice received an intracerebroventricular injection of the immunotoxin p75NTR mu-saporin to induce the loss of cholinergic neurons. Quadruple labeling immunohistochemistry and 3D reconstruction were carried out to characterize specific points of contact between cholinergic fibers and collagen IV, smooth muscle cells and astrocyte endfeet. Innate differences were observed between vessels of the hippocampus and cortex of control mice, including a greater amount of cholinergic contact with perivascular astrocytes in hippocampal capillaries and a thicker basement membrane in hippocampal veins. Saporin treatment induced a loss of cholinergic innervation at the arterial basement membrane and smooth muscle cells of both the hippocampus and the cortex. In the cortex, there was an additional loss of innervation at the astrocytic endfeet. The current results suggest that cortical arteries are more strongly affected by cholinergic denervation than arteries in the hippocampus. This regional variation may have implications for the etiology of the vascular pathology that develops in AD.
| Type: | Article |
|---|---|
| Title: | 3D Reconstruction of the Neurovascular Unit Reveals Differential Loss of Cholinergic Innervation in the Cortex and Hippocampus of the Adult Mouse Brain |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fnagi.2019.00172 |
| Publisher version: | https://doi.org/10.3389/fnagi.2019.00172 |
| Language: | English |
| Additional information: | Copyright © 2019 Nizari, Carare, Romero and Hawkes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/). 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. |
| Keywords: | Neurovascular unit, cholinergic, Alzheimer’s disease, cerebral amyloid angiopathy, cortex, hippocampus |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Imaging UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10149364 |
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