Nasim F Mehrabi1, Henry J Waldvogel1, Lynette J Tippett2, Virginia M Hogg2, Beth J Synek3, Richard L M Faull4. 1. Centre for Brain Research, University of Auckland, Auckland, New Zealand; Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand. 2. Centre for Brain Research, University of Auckland, Auckland, New Zealand; Department of Psychology, University of Auckland, Auckland, New Zealand. 3. Centre for Brain Research, University of Auckland, Auckland, New Zealand; Forensic Pathology, Auckland City Hospital, Auckland, New Zealand. 4. Centre for Brain Research, University of Auckland, Auckland, New Zealand; Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand. Electronic address: rlm.faull@auckland.ac.
Abstract
BACKGROUND: Huntington's disease (HD) is characterised by variable symptoms and neuropathology of the basal ganglia and cortex. Previously, we have shown that the pattern of pyramidal cell loss in 8 different cortical regions correlates with the phenotypic variability in HD. In the primary motor and anterior cingulate cortices, the pattern of interneuron degeneration correlates with pyramidal cell death and variable HD symptom profiles. OBJECTIVES: This study aimed to examine the pattern of interneuron degeneration in 3 further regions of the HD cortex (primary sensory, superior frontal, superior parietal cortices) to determine whether HD neuropathogenesis was characterised by a general fundamental pattern of cortical interneuron loss, and explore the relationship between cortical interneuron loss with previously determined pyramidal cell loss and clinical heterogeneity. METHODS: Stereological counting was used to quantify 3 sub-populations of calcium-binding protein containing interneurons in 3 cortical human brain regions of 14 HD and 13 control cases as used in our previous studies (Nana et al., 2014; Kim et al., 2014). The HD cases were grouped according to their predominant symptom profile ("motor", "mood", "mixed"). RESULTS: The present results demonstrated a heterogeneous loss of interneurons across the 3 cortical regions which, when compared with our previous studies, mirrored the pattern of pyramidal cell loss in the same cortical areas. Most interestingly, the pattern of neuronal loss in these regions correlated with the variable HD symptom profiles. CONCLUSION: The overall findings in our present and previous cortical studies establish a clear correlative pattern of variable cortical neuronal degeneration in HD pathogenesis, which mirrors the heterogeneity of HD symptom phenotypes.
BACKGROUND:Huntington's disease (HD) is characterised by variable symptoms and neuropathology of the basal ganglia and cortex. Previously, we have shown that the pattern of pyramidal cell loss in 8 different cortical regions correlates with the phenotypic variability in HD. In the primary motor and anterior cingulate cortices, the pattern of interneuron degeneration correlates with pyramidal cell death and variable HD symptom profiles. OBJECTIVES: This study aimed to examine the pattern of interneuron degeneration in 3 further regions of the HD cortex (primary sensory, superior frontal, superior parietal cortices) to determine whether HD neuropathogenesis was characterised by a general fundamental pattern of cortical interneuron loss, and explore the relationship between cortical interneuron loss with previously determined pyramidal cell loss and clinical heterogeneity. METHODS: Stereological counting was used to quantify 3 sub-populations of calcium-binding protein containing interneurons in 3 cortical human brain regions of 14 HD and 13 control cases as used in our previous studies (Nana et al., 2014; Kim et al., 2014). The HD cases were grouped according to their predominant symptom profile ("motor", "mood", "mixed"). RESULTS: The present results demonstrated a heterogeneous loss of interneurons across the 3 cortical regions which, when compared with our previous studies, mirrored the pattern of pyramidal cell loss in the same cortical areas. Most interestingly, the pattern of neuronal loss in these regions correlated with the variable HD symptom profiles. CONCLUSION: The overall findings in our present and previous cortical studies establish a clear correlative pattern of variable cortical neuronal degeneration in HD pathogenesis, which mirrors the heterogeneity of HD symptom phenotypes.
Authors: Mark F Mehler; Jenna R Petronglo; Eduardo E Arteaga-Bracho; Maria E Gulinello; Michael L Winchester; Nandini Pichamoorthy; Stephen K Young; Christopher D DeJesus; Hifza Ishtiaq; Solen Gokhan; Aldrin E Molero Journal: J Neurosci Date: 2019-01-09 Impact factor: 6.167
Authors: Malvindar K Singh-Bains; Nasim F Mehrabi; Adelie Y S Tan; Richard L M Faull; Mike Dragunow Journal: Nat Protoc Date: 2021-03-19 Impact factor: 13.491
Authors: Malvindar K Singh-Bains; Nasim F Mehrabi; Tvesa Sehji; Micah D R Austria; Adelie Y S Tan; Lynette J Tippett; Mike Dragunow; Henry J Waldvogel; Richard L M Faull Journal: Ann Neurol Date: 2019-02-04 Impact factor: 10.422
Authors: Christopher D Rowley; Sarah J Tabrizi; Rachael I Scahill; Blair R Leavitt; Raymund A C Roos; Alexandra Durr; Nicholas A Bock Journal: Front Neurosci Date: 2018-11-05 Impact factor: 4.677