Document Detail


Spatiotemporal analysis of purkinje cell degeneration relative to parasagittal expression domains in a model of neonatal viral infection.
MedLine Citation:
PMID:  17182680     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Infection of newborn Lewis rats with Borna disease virus (neonatal Borna disease [NBD]) results in cerebellar damage without the cellular inflammation associated with infections in later life. Purkinje cell (PC) damage has been reported for several models of early-life viral infection, including NBD; however, the time course and distribution of PC pathology have not been investigated rigorously. This study examined the spatiotemporal relationship between PC death and zonal organization in NBD cerebella. Real-time PCR at postnatal day 28 (PND28) revealed decreased cerebellar levels of mRNAs encoding the glycolytic enzymes aldolase C (AldoC, also known as zebrin II) and phosphofructokinase C and the excitatory amino acid transporter 4 (EAAT4). Zebrin II and EAAT4 immunofluorescence analysis in PND21, PND28, PND42, and PND84 NBD rat cerebella revealed a complex pattern of PC degeneration. Early cell loss (PND28) was characterized by preferential apoptotic loss of zebrin II/EAAT4-negative PC subsets in the anterior vermis. Consistent with early preferential loss of zebrin II/EAAT4-negative PCs in the vermis, the densities of microglia and the Bergmann glial expression of metallothionein I/II and the hyaluronan receptor CD44 were higher in zebrin II/EAAT4-negative zones. In contrast, early loss in lateral cerebellar lobules did not reflect a similar discrimination between PC phenotypes. Patterns of vermal PC loss became more heterogeneous at PND42, with the loss of both zebrin II/EAAT4-negative and zebrin II/EAAT4-positive neurons. At PND84, zebrin II/EAAT4 patterning was abolished in the anterior cerebellum, with preferential PC survival in lobule X. Our investigation reveals regional discrimination between patterns of PC subset loss, defined by zebrin II/EAAT4 expression domains, following neonatal viral infection. These findings suggest a differential vulnerability of PC subsets during the early stages of virus-induced neurodegeneration.
Authors:
Brent L Williams; Kavitha Yaddanapudi; Mady Hornig; W Ian Lipkin
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-12-20
Journal Detail:
Title:  Journal of virology     Volume:  81     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-26     Completed Date:  2007-04-04     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2675-87     Citation Subset:  IM    
Affiliation:
Jerome L. and Dawn Greene Infectious Disease Laboratory, Mailman School of Public Health, Columbia University, 722 West 168th Street, Rm. 1801, New York, NY 10032, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Borna Disease / metabolism*,  pathology
Borna disease virus*
Calcium-Binding Protein, Vitamin D-Dependent / metabolism
Cell Death
Cerebellum / physiopathology
Excitatory Amino Acid Transporter 4 / analysis,  metabolism
Fluorescent Antibody Technique, Indirect
Kinetics
Models, Neurological
Nerve Tissue Proteins / analysis,  metabolism
Oligonucleotide Array Sequence Analysis
Phosphofructokinase-1, Type C / analysis,  metabolism
Polymerase Chain Reaction
Purkinje Cells / physiology*
RNA, Messenger / analysis
Rats
Rats, Inbred Lew
Grant Support
ID/Acronym/Agency:
HD 37546/HD/NICHD NIH HHS; MH 01608/MH/NIMH NIH HHS; NS 29425/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Calcium-Binding Protein, Vitamin D-Dependent; 0/Excitatory Amino Acid Transporter 4; 0/Nerve Tissue Proteins; 0/RNA, Messenger; 0/Slc1a6 protein, rat; 0/calbindin; 0/zebrin II; EC 2.7.1.-/Phosphofructokinase-1, Type C
Comments/Corrections

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