TY - JOUR
T1 - Microglia Activation in Basal Ganglia Is a Late Event in Huntington Disease Pathophysiology
AU - Rocha, Natalia P.
AU - Charron, Odelin
AU - Latham, Leigh B.
AU - Colpo, Gabriela D.
AU - Zanotti-Fregonara, Paolo
AU - Yu, Meixiang
AU - Freeman, Leorah
AU - Stimming, Erin Furr
AU - Teixeira, Antonio L.
N1 - Funding Information:
The Article Processing Charge was funded by the Department of Psychiatry and Behavioral Sciences, UTHealth.
Funding Information:
This study was funded by the HD Human Biology Project—Huntington's Disease Society of America (HDSA). E. Furr Stimming receives research funding from Roche/Genetech, Vaccinex, Cures Within Reach, HDSA, Uniqure, and CHDI Foundation.
Publisher Copyright:
© American Academy of Neurology.
PY - 2021/5/31
Y1 - 2021/5/31
N2 - ObjectiveTo define the role played by microglia in different stages of Huntington disease (HD), we used the TSPO radioligand [11C]-ER176 and PET to evaluate microglial activation in relation to neurodegeneration and in relation to the clinical features seen at premanifest and manifest stages of the disease.MethodsThis is a cross-sectional study in which 18 subjects (6 controls, 6 premanifest, and 6 manifest HD gene carriers) underwent a [11C]-ER176 PET scan and an MRI for anatomic localization. Segmentation of regions of interest (ROIs) was performed, and group differences in [11C]-ER176 binding (used to evaluate the extent of microglial activation) were assessed by the standardized uptake value ratio (SUVR). Microglial activation was correlated with ROIs volumes, disease burden, and the scores obtained in the clinical scales. As an exploratory aim, we evaluated the dynamic functions of microglia in vitro, by using induced microglia-like (iMG) cells from peripheral blood monocytes.ResultsIndividuals with manifest HD present higher [11C]-ER176 SUVR in both globi pallidi and putamina in comparison with controls. No differences were observed when we compared premanifest HD with controls or with manifest HD. We also found a significant correlation between increased microglial activation and cumulative disease burden, and with reduced volumes. iMG from controls, premanifest HD, and manifest HD patients showed similar phagocytic capacity.ConclusionsAltogether, our data demonstrate that microglial activation is involved in HD pathophysiology and is associated with disease progression.
AB - ObjectiveTo define the role played by microglia in different stages of Huntington disease (HD), we used the TSPO radioligand [11C]-ER176 and PET to evaluate microglial activation in relation to neurodegeneration and in relation to the clinical features seen at premanifest and manifest stages of the disease.MethodsThis is a cross-sectional study in which 18 subjects (6 controls, 6 premanifest, and 6 manifest HD gene carriers) underwent a [11C]-ER176 PET scan and an MRI for anatomic localization. Segmentation of regions of interest (ROIs) was performed, and group differences in [11C]-ER176 binding (used to evaluate the extent of microglial activation) were assessed by the standardized uptake value ratio (SUVR). Microglial activation was correlated with ROIs volumes, disease burden, and the scores obtained in the clinical scales. As an exploratory aim, we evaluated the dynamic functions of microglia in vitro, by using induced microglia-like (iMG) cells from peripheral blood monocytes.ResultsIndividuals with manifest HD present higher [11C]-ER176 SUVR in both globi pallidi and putamina in comparison with controls. No differences were observed when we compared premanifest HD with controls or with manifest HD. We also found a significant correlation between increased microglial activation and cumulative disease burden, and with reduced volumes. iMG from controls, premanifest HD, and manifest HD patients showed similar phagocytic capacity.ConclusionsAltogether, our data demonstrate that microglial activation is involved in HD pathophysiology and is associated with disease progression.
UR - http://www.scopus.com/inward/record.url?scp=85103807384&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103807384&partnerID=8YFLogxK
U2 - 10.1212/NXI.0000000000000984
DO - 10.1212/NXI.0000000000000984
M3 - Article
C2 - 33795375
AN - SCOPUS:85103807384
SN - 2332-7812
VL - 8
JO - Neurology: Neuroimmunology and NeuroInflammation
JF - Neurology: Neuroimmunology and NeuroInflammation
IS - 3
M1 - e982
ER -