Purkinje cell loss in experimental autoimmune encephalomyelitis.
Gray matter atrophy observed by brain MRI is an important correlate to clinical disability and disease duration in multiple sclerosis. The objective of this study was to link brain atrophy visualized by neuroimaging to its underlying neuropathology using the MS model, experimental autoimmune encephalomyelitis (EAE). Volumetric changes in brains of EAE mice, as well as matched healthy normal controls, were quantified by collecting post-mortem high-resolution T2-weighted magnetic resonance microscopy and actively stained magnetic resonance histology images. Anatomical delineations demonstrated a significant decrease in the volume of the whole cerebellum, cerebellar cortex, and molecular layer of the cerebellar cortex in EAE as compared to normal controls. The pro-apoptotic marker caspase-3 was detected in Purkinje cells and a significant decrease in Purkinje cell number was found in EAE. Cross modality and temporal correlations revealed a significant association between Purkinje cell loss on neuropathology and atrophy of the molecular layer of the cerebellar cortex by neuroimaging. These results demonstrate the power of using combined population atlasing and neuropathology approaches to discern novel insights underlying gray matter atrophy in animal models of neurodegenerative disease.
MacKenzie-Graham
Allan
A
Laboratory of Neuro Imaging, Suite 225, Los Angeles, CA 90095-1769, USA.
Tiwari-Woodruff
Seema K
SK
Sharma
Gaurav
G
Aguilar
Cynthia
C
Vo
Kieumai T
KT
Strickland
Lauren V
LV
Morales
Laurie
L
Fubara
Boma
B
Martin
Melanie
M
Jacobs
Russell E
RE
Johnson
G Allan
GA
Toga
Arthur W
AW
Voskuhl
Rhonda R
RR
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001284:Atrophy; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D002531:Cerebellum / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis; D009929:Organ Size; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; C505409:Casp3 protein, mouse; D053148:Caspase 3