title: Reduced Purkinje cell dendritic arborization and loss of dendritic spines in essential tremor.
abstract: Based on accumulating post-mortem evidence of abnormalities in Purkinje cell biology in essential tremor, we hypothesized that regressive changes in dendritic morphology would be apparent in the Purkinje cell population in essential tremor cases versus age-matched controls. Cerebellar cortical tissue from 27 cases with essential tremor and 27 age-matched control subjects was processed by the Golgi-Kopsch method. Purkinje cell dendritic anatomy was quantified using a Neurolucida microscopic system interfaced with a motorized stage. In all measures, essential tremor cases demonstrated significant reductions in dendritic complexity compared with controls. Median values in essential tremor cases versus controls were: 5712.1 versus 10 403.2 µm (total dendrite length, P=0.01), 465.9 versus 592.5 µm (branch length, P=0.01), 22.5 versus 29.0 (maximum branch order, P=0.001), and 165.3 versus 311.7 (number of terminations, P=0.008). Furthermore, the dendritic spine density was reduced in essential tremor cases (medians=0.82 versus 1.02 µm(-1), P=0.03). Our demonstration of regressive changes in Purkinje cell dendritic architecture and spines in essential tremor relative to control brains provides additional evidence of a pervasive abnormality of Purkinje cell biology in this disease, which affects multiple neuronal cellular compartments including their axon, cell body, dendrites and spines.
authors.affiliation: 1 GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA 2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA 3 Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA 4 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA EDL2@columbia.edu.
authors.forename: Elan D
authors.initials: ED
authors.lastname: Louis
authors.affiliation: 1 GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lee
authors.affiliation: 1 GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA 2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Babij
authors.affiliation: 1 GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA 2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Ma
authors.affiliation: 5 Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY 10032, USA.
authors.forename: Etty
authors.initials: E
authors.lastname: Cortés
authors.affiliation: 2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA 5 Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY 10032, USA.
authors.forename: Jean-Paul G
authors.initials: JP
authors.lastname: Vonsattel
authors.affiliation: 5 Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY 10032, USA.
authors.forename: Phyllis L
authors.initials: PL
authors.lastname: Faust
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D001369:Axons / Q000473:pathology; D002531:Cerebellum / Q000473:pathology*; D049229:Dendritic Spines / Q000473:pathology*; D020329:Essential Tremor / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D009474:Neurons / Q000166:cytology; D011689:Purkinje Cells / Q000473:pathology*
keywords: Purkinje cell; biology; cerebellum; essential tremor; neurodegenerative