Brain pericyte activation occurs early in Huntington's disease

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T1 - Brain pericyte activation occurs early in Huntington's disease

AU - Padel, Thomas

AU - Roth, Michaela

AU - Gaceb, Abderahim

AU - Li, Jia Yi

AU - Björkqvist, Maria

AU - Paul, Gesine

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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.

AB - 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.

KW - Brain vasculature

KW - Huntington's disease

KW - Pericyte

KW - Regulator of G-protein signaling 5

U2 - 10.1016/j.expneurol.2018.03.015

DO - 10.1016/j.expneurol.2018.03.015

M3 - Article

VL - 305

SP - 139

EP - 150

JO - Neurodegeneration

T2 - Neurodegeneration

JF - Neurodegeneration

SN - 0014-4886

ER -