Microglial and Astrocytic Responses in the Human Midcingulate Cortex in Huntington's Disease-Reference-Cited by-同舟云学术

Microglial and Astrocytic Responses in the Human Midcingulate Cortex in Huntington's Disease

Published:2023-08-16 Issue:5 Volume:94 Page:895-910
ISSN:0364-5134
Container-title:Annals of Neurology
language:en
Short-container-title:Annals of Neurology

Author:

Palpagama Thulani¹,Mills Aimee Rose¹,Ferguson Mackenzie Wendy¹,Vikas Ankeal Praju²,Turner Clinton³,Tippett Lynette⁴,van der Werf Bert⁵,Waldvogel Henry John¹,Faull Richard Lewis Maxwell¹,Kwakowsky Andrea¹⁶^ORCID

Affiliation:

1. Centre for Brain Research and Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences University of Auckland Auckland New Zealand

2. MicRoN, Harvard Medical School Harvard University Cambridge MA

3. Department of Anatomical Pathology, LabPlus Auckland City Hospital Auckland New Zealand

4. Centre for Brain Research and School of Psychology, Faculty of Sciences University of Auckland Auckland New Zealand

5. Department of Epidemiology and Biostatistics, Faculty of Medical and Health Sciences, School of Population Health University of Auckland Auckland New Zealand

6. Pharmacology and Therapeutics, School of Medicine, Galway Neuroscience Centre University of Galway Galway Ireland

Abstract

ObjectivePatients with Huntington's disease can present with variable difficulties of motor functioning, mood, and cognition. Neurodegeneration occurs in the anterior cingulate cortex of some patients with Huntington's disease and is linked to the presentation of mood symptomatology. Neuroinflammation, perpetrated by activated microglia and astrocytes, has been reported in Huntington's disease and may contribute to disease progression and presentation. This study sought to quantify the density of mutant huntingtin protein and neuroinflammatory glial changes in the midcingulate cortex of postmortem patients with Huntington's disease and determine if either correlates with the presentation of mood, motor, or mixed symptomatology.MethodsFree‐floating immunohistochemistry quantified 1C2 immunolabeling density as an indicative marker of mutant huntingtin protein, and protein and morphological markers of astrocyte (EAAT2, Cx43, and GFAP), and microglial (Iba1 and HLA‐DP/DQ/DR) activation. Relationships among the level of microglial activation, mutant huntingtin burden, and case characteristics were explored using correlative analysis.ResultsWe report alterations in activated microglia number and morphology in the midcingulate cortex of Huntington's disease cases with predominant mood symptomatology. An increased proportion of activated microglia was observed in the midcingulate of all Huntington's disease cases and positively correlated with 1C2 burden. Alterations in the astrocytic glutamate transporter EAAT2 were observed in the midcingulate cortex of patients associated with mood symptoms.InterpretationThis study presents pathological changes in microglia and astrocytes in the midcingulate cortex in Huntington's disease, which coincide with mood symptom presentation. These findings further the understanding of neuroinflammation in Huntington's disease, a necessary step for developing inflammation‐targeted therapeutics. ANN NEUROL 2023;94:895–910

Funder

Aotearoa Foundation

Freemasons New Zealand

Health Research Council of New Zealand

Maurice and Phyllis Paykel Trust

Neurological Foundation of New Zealand

Oakley Mental Health Research Foundation

Publisher

Wiley

Subject

Neurology (clinical),Neurology

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