TY - JOUR
T1 - Purkinje cell axonal anatomy
T2 - Quantifying morphometric changes in essential tremor versus control brains
AU - Babij, Rachel
AU - Lee, Michelle
AU - Cortés, Etty
AU - Vonsattel, Jean Paul G.
AU - Faust, Phyllis L.
AU - Louis, Elan D.
N1 - Funding Information:
Dr. Vonsattel has received funding from NINDS #R01 NS39422 (co-investigator), Dr. Faust has received funding from NINDS #R21 NS077094 (principle Investigator) and NINDS #R01 NS39422 (co-investigator), Dr. Louis has received research support from the National Institutes of Health: NINDS #R01 NS042859 (principal investigator), NINDS #R01 NS39422 (principal investigator), NINDS #T32 NS07153-24 (principal investigator), NINDS #R01 NS073872 (principal investigator), NINDS #R21 NS077094 (co-Investigator), NINDS #R01 NS36630 (co-Investigator), NIEHS P30 ES09089 (co-investigator, and CTSA grant number UL1 RR024156. 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). Tissue on 14 control brains was contributed by the Harvard Brain Tissue Resource Center, which is supported in part by PHS grant number R24 MH068855.
PY - 2013/10
Y1 - 2013/10
N2 - Growing clinical, neuro-imaging and post-mortem data have implicated the cerebellum as playing an important role in the pathogenesis of essential tremor. Aside from a modest reduction of Purkinje cells in some post-mortem studies, Purkinje cell axonal swellings (torpedoes) are present to a greater degree in essential tremor cases than controls. Yet a detailed study of more subtle morphometric changes in the Purkinje cell axonal compartment has not been undertaken. We performed a detailed morphological analysis of the Purkinje cell axonal compartment in 49 essential tremor and 39 control brains, using calbindin D28k immunohistochemistry on 100-m cerebellar cortical vibratome tissue sections. Changes in axonal shape [thickened axonal profiles (P = 0.006), torpedoes (P = 0.038)] and changes in axonal connectivity [axonal recurrent collaterals (P < 0.001), axonal branching (P < 0.001), terminal axonal sprouting (P < 0.001)] were all present to an increased degree in essential tremor cases versus controls. The changes in shape and connectivity were significantly correlated [e.g. correlation between thickened axonal profiles and recurrent collaterals (r = 0.405, P < 0.001)] and were correlated with tremor duration among essential tremor cases with age of onset >40 years. In essential tremor cases, thickened axonal profiles, axonal recurrent collaterals and branched axons were 3- to 5-fold more frequently seen on the axons of Purkinje cells with torpedoes versus Purkinje cells without torpedoes. We document a range of changes in the Purkinje cell axonal compartment in essential tremor. Several of these are likely to be compensatory changes in response to Purkinje cell injury, thus illustrating an important feature of Purkinje cells, which is that they are relatively resistant to damage and capable of mobilizing a broad range of axonal responses to injury. The extent to which this plasticity of the Purkinje cell axon is partially neuroprotective or ultimately ineffective at slowing further cellular changes and cell death deserves further study in essential tremor.
AB - Growing clinical, neuro-imaging and post-mortem data have implicated the cerebellum as playing an important role in the pathogenesis of essential tremor. Aside from a modest reduction of Purkinje cells in some post-mortem studies, Purkinje cell axonal swellings (torpedoes) are present to a greater degree in essential tremor cases than controls. Yet a detailed study of more subtle morphometric changes in the Purkinje cell axonal compartment has not been undertaken. We performed a detailed morphological analysis of the Purkinje cell axonal compartment in 49 essential tremor and 39 control brains, using calbindin D28k immunohistochemistry on 100-m cerebellar cortical vibratome tissue sections. Changes in axonal shape [thickened axonal profiles (P = 0.006), torpedoes (P = 0.038)] and changes in axonal connectivity [axonal recurrent collaterals (P < 0.001), axonal branching (P < 0.001), terminal axonal sprouting (P < 0.001)] were all present to an increased degree in essential tremor cases versus controls. The changes in shape and connectivity were significantly correlated [e.g. correlation between thickened axonal profiles and recurrent collaterals (r = 0.405, P < 0.001)] and were correlated with tremor duration among essential tremor cases with age of onset >40 years. In essential tremor cases, thickened axonal profiles, axonal recurrent collaterals and branched axons were 3- to 5-fold more frequently seen on the axons of Purkinje cells with torpedoes versus Purkinje cells without torpedoes. We document a range of changes in the Purkinje cell axonal compartment in essential tremor. Several of these are likely to be compensatory changes in response to Purkinje cell injury, thus illustrating an important feature of Purkinje cells, which is that they are relatively resistant to damage and capable of mobilizing a broad range of axonal responses to injury. The extent to which this plasticity of the Purkinje cell axon is partially neuroprotective or ultimately ineffective at slowing further cellular changes and cell death deserves further study in essential tremor.
KW - Purkinje cell
KW - axon
KW - essential tremor
KW - neurodegenerative
KW - recurrent collateral
UR - http://www.scopus.com/inward/record.url?scp=84884838268&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884838268&partnerID=8YFLogxK
U2 - 10.1093/brain/awt238
DO - 10.1093/brain/awt238
M3 - Article
C2 - 24030953
AN - SCOPUS:84884838268
SN - 0006-8950
VL - 136
SP - 3051
EP - 3061
JO - Brain
JF - Brain
IS - 10
ER -