title: Characterization of gray matter atrophy following 6-hydroxydopamine lesion of the nigrostriatal system.
abstract: BACKGROUND
  The unilaterally-lesioned 6-hydroxydopamine (6-OHDA) rat is one of the most commonly used experimental models of Parkinson's disease (PD). Here we investigated whether magnetic resonance imaging (MRI) that is widely used in human PD research, has the potential to non-invasively detect macroscopic structural brain changes in the 6-OHDA rat in ways translatable to humans.
  
  
  METHODS
  We measured the gray matter (GM) composition in the unilateral 6-OHDA rat in comparison to sham animals using whole-brain voxel-based morphometry (VBM) - an unbiased MR image analysis technique. The number of nigral dopamine (DA) neurons and the density of their cortical projections were examined post-mortem using immunohistochemistry.
  
  
  RESULTS
  VBM revealed widespread bilateral changes in gray matter volume (GMV) on a topographic scale in the brains of 6-OHDA rats, compared to sham-operated rats. The greatest changes were in the lesioned hemisphere, which displayed reductions of GMV in motor, cingulate and somatosensory cortex. Histopathological results revealed dopaminergic cell loss in the substantia nigra (SN) and a denervation in the striatum, as well as in the frontal, somatosensory and cingulate cortices.
  
  
  CONCLUSIONS
  Unilateral nigrostriatal 6-OHDA lesioning leads to widespread GMV changes, which extend beyond the nigrostriatal system and resemble advanced Parkinsonism. This study highlights the potential of structural MRI, and VBM in particular, for the system-level phenotyping of rodent models of Parkinsonism and provides a methodological framework for future studies in novel rodent models as they become available to the research community.
authors: Department of Neuroimaging, King's College London, Institute of Psychiatry, Psychology & Neuroscience, UK. Electronic address: robert.westphal@psych.ox.ac.uk.
authors: Robert
authors: R
authors: Westphal
authors: Institute of Development, Ageing and Cancer, Tohoku University, Japan.
authors: Akira
authors: A
authors: Sumiyoshi
authors: Department of Neuroimaging, King's College London, Institute of Psychiatry, Psychology & Neuroscience, UK.
authors: Camilla
authors: C
authors: Simmons
authors: Department of Neuroimaging, King's College London, Institute of Psychiatry, Psychology & Neuroscience, UK.
authors: Michel
authors: M
authors: Mesquita
authors: Department of Neuroimaging, King's College London, Institute of Psychiatry, Psychology & Neuroscience, UK.
authors: Tobias C
authors: TC
authors: Wood
authors: Department of Neuroimaging, King's College London, Institute of Psychiatry, Psychology & Neuroscience, UK.
authors: Steve C R
authors: SC
authors: Williams
authors: Department of Basic and Clinical Neuroscience, King's College London, Institute of Psychiatry, Psychology & Neuroscience, UK.
authors: Anthony C
authors: AC
authors: Vernon
authors: Department of Neuroimaging, King's College London, Institute of Psychiatry, Psychology & Neuroscience, UK.
authors: Diana
authors: D
authors: Cash
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001284:Atrophy / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D018491:Dopamine Agonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007839:Functional Laterality; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine
keywords: 6-OHDA; Parkinson’s disease; brain; magnetic resonance imaging; rat; voxel-based morphometry