Brain pericyte activation occurs early in Huntington's disease
Padel, Thomas LU ; Roth, Michaela LU ; Gaceb, Abderahim LU ; Li, Jia Yi LU ; Björkqvist, Maria LU
and Paul, Gesine
LU
(2018)
In Experimental Neurology
305.
p.139-150
- Abstract
Microvascular changes have recently been described for several neurodegenerative disorders, including Huntington's disease (HD). HD is characterized by a progressive neuronal cell loss due to a mutation in the Huntingtin gene. However, the temporal and spatial microvascular alterations in HD remain unclear. Also, knowledge on the implication of pericytes in HD pathology is still sparse and existing findings are contradictory. Here we examine alterations in brain pericytes in the R6/2 mouse model of HD and in human post mortem HD brain sections. To specifically track activated pericytes, we crossbred R6/2 mice with transgenic mice expressing the Green fluorescent protein gene under the Regulator of G-protein signaling 5 (Rgs5) promoter.... (More)
Microvascular changes have recently been described for several neurodegenerative disorders, including Huntington's disease (HD). HD is characterized by a progressive neuronal cell loss due to a mutation in the Huntingtin gene. However, the temporal and spatial microvascular alterations in HD remain unclear. Also, knowledge on the implication of pericytes in HD pathology is still sparse and existing findings are contradictory. Here we examine alterations in brain pericytes in the R6/2 mouse model of HD and in human post mortem HD brain sections. To specifically track activated pericytes, we crossbred R6/2 mice with transgenic mice expressing the Green fluorescent protein gene under the Regulator of G-protein signaling 5 (Rgs5) promoter. We demonstrate an increase in activated pericytes in the R6/2 brain and in post mortem HD brain tissue. Importantly, pericyte changes are already detected before striatal neuronal cell loss, weight loss or behavioural deficits occur in R6/2 mice. This is associated with vascular alterations, whereby striatal changes precede cortical changes. Our findings suggest that pericyte activation may be one of the initial steps contributing to the observed vascular modifications in HD. Thus, pericytes may constitute an important target to address early microvascular changes contributing to disease progression in HD.
(Less)
- author
- Padel, Thomas
LU
; Roth, Michaela
LU
; Gaceb, Abderahim
LU
; Li, Jia Yi
LU
; Björkqvist, Maria
LU
and Paul, Gesine
LU
- organization
- publishing date
- 2018-07-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Brain vasculature, Huntington's disease, Pericyte, Regulator of G-protein signaling 5
- in
- Experimental Neurology
- volume
- 305
- pages
- 12 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:85045726123
- pmid:29630897
- ISSN
- 0014-4886
- DOI
- 10.1016/j.expneurol.2018.03.015
- language
- English
- LU publication?
- yes
- id
- 3284bc20-ddf0-4f2d-ac7a-043421f0f449
- date added to LUP
- 2018-05-22 13:25:50
- date last changed
- 2024-06-24 14:41:19
@article{3284bc20-ddf0-4f2d-ac7a-043421f0f449,
abstract = {{<p>Microvascular changes have recently been described for several neurodegenerative disorders, including Huntington's disease (HD). HD is characterized by a progressive neuronal cell loss due to a mutation in the Huntingtin gene. However, the temporal and spatial microvascular alterations in HD remain unclear. Also, knowledge on the implication of pericytes in HD pathology is still sparse and existing findings are contradictory. Here we examine alterations in brain pericytes in the R6/2 mouse model of HD and in human post mortem HD brain sections. To specifically track activated pericytes, we crossbred R6/2 mice with transgenic mice expressing the Green fluorescent protein gene under the Regulator of G-protein signaling 5 (Rgs5) promoter. We demonstrate an increase in activated pericytes in the R6/2 brain and in post mortem HD brain tissue. Importantly, pericyte changes are already detected before striatal neuronal cell loss, weight loss or behavioural deficits occur in R6/2 mice. This is associated with vascular alterations, whereby striatal changes precede cortical changes. Our findings suggest that pericyte activation may be one of the initial steps contributing to the observed vascular modifications in HD. Thus, pericytes may constitute an important target to address early microvascular changes contributing to disease progression in HD.</p>}},
author = {{Padel, Thomas and Roth, Michaela and Gaceb, Abderahim and Li, Jia Yi and Björkqvist, Maria and Paul, Gesine}},
issn = {{0014-4886}},
keywords = {{Brain vasculature; Huntington's disease; Pericyte; Regulator of G-protein signaling 5}},
language = {{eng}},
month = {{07}},
pages = {{139--150}},
publisher = {{Elsevier}},
series = {{Experimental Neurology}},
title = {{Brain pericyte activation occurs early in Huntington's disease}},
url = {{http://dx.doi.org/10.1016/j.expneurol.2018.03.015}},
doi = {{10.1016/j.expneurol.2018.03.015}},
volume = {{305}},
year = {{2018}},
}