TY - JOUR
T1 - Reduced Purkinje cell dendritic arborization and loss of dendritic spines in essential tremor
AU - Louis, Elan D.
AU - Lee, Michelle
AU - Babij, Rachel
AU - Ma, Karen
AU - Cortés, Etty
AU - Vonsattel, Jean Paul G.
AU - Faust, Phyllis L.
N1 - Funding Information:
Dr Louis has received research support from the National Institutes of Health: NINDS #R01 NS042859 (principal investigator), NINDS #R01 NS39422 (principal investigator), NINDS #R01 NS086736 (principal investigator), NINDS #R01 NS073872 (principal investigator), NINDS #R01 NS085136 (principal investigator), NINDS #T32 NS07153-24 (principal investigator), NINDS #R21 NS077094 (co-Investigator), NINDS #R01 NS36630 (coInvestigator) and NIEHS P30 ES09089 (co-investigator). He has also received support from Parkinson’s Disease Foundation, the Arlene Bronstein Essential Tremor Research Fund (Columbia University), and the Claire O’Neil Essential Tremor Research Fund (Columbia University). Dr Faust has received funding from NINDS #R21 NS077094 (principle Investigator) and NINDS #R01 NS39422 (co-investigator). Dr Vonsattel has received funding from NINDS #R01 NS39422 (co-investigator).
Funding Information:
We thank the Harvard Brain Tissue Resource Centre (supported in part by PHS grant number R24 MH068855) for providing control tissue. We similarly thank the University of Kentucky Alzheimer’s Disease Centre Biobank (P30 AG028383) for providing control tissue, and the patients, staff, and clinicians who have contributed to their efforts. We thank Bob Jacobs PhD, Colorado College, for providing guidance on Golgi methods. We thank Andrew Dwork, MD, Columbia University, for providing equipment and expertise with Golgi methods and Neurolucida microscopy.
Publisher Copyright:
© 2014 The Author.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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.
AB - 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.
KW - Biology
KW - Cerebellum
KW - Essential tremor
KW - Neurodegenerative
KW - Purkinje cell
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U2 - 10.1093/brain/awu314
DO - 10.1093/brain/awu314
M3 - Article
C2 - 25367027
AN - SCOPUS:84922354068
SN - 0006-8950
VL - 137
SP - 3142
EP - 3148
JO - Brain
JF - Brain
IS - 12
ER -