PMID- 17182680 OWN - NLM STAT- MEDLINE DCOM- 20070404 LR - 20181113 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 81 IP - 6 DP - 2007 Mar TI - Spatiotemporal analysis of purkinje cell degeneration relative to parasagittal expression domains in a model of neonatal viral infection. PG - 2675-87 AB - 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. FAU - Williams, Brent L AU - Williams BL AD - 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. FAU - Yaddanapudi, Kavitha AU - Yaddanapudi K FAU - Hornig, Mady AU - Hornig M FAU - Lipkin, W Ian AU - Lipkin WI LA - eng GR - R01 HD037546/HD/NICHD NIH HHS/United States GR - HD 37546/HD/NICHD NIH HHS/United States GR - MH 01608/MH/NIMH NIH HHS/United States GR - NS 29425/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20061220 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Calbindins) RN - 0 (Excitatory Amino Acid Transporter 4) RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA, Messenger) RN - 0 (S100 Calcium Binding Protein G) RN - 0 (Slc1a6 protein, rat) RN - 0 (zebrin II) RN - EC 2.7.1.- (Phosphofructokinase-1, Type C) SB - IM MH - Animals MH - Animals, Newborn MH - Borna Disease/*metabolism/pathology MH - *Borna disease virus MH - Calbindins MH - Cell Death MH - Cerebellum/physiopathology MH - Excitatory Amino Acid Transporter 4/analysis/metabolism MH - Fluorescent Antibody Technique, Indirect MH - Kinetics MH - Models, Neurological MH - Nerve Tissue Proteins/analysis/metabolism MH - Oligonucleotide Array Sequence Analysis MH - Phosphofructokinase-1, Type C/analysis/metabolism MH - Polymerase Chain Reaction MH - Purkinje Cells/*physiology MH - RNA, Messenger/analysis MH - Rats MH - Rats, Inbred Lew MH - S100 Calcium Binding Protein G/metabolism PMC - PMC1865998 EDAT- 2006/12/22 09:00 MHDA- 2007/04/05 09:00 PMCR- 2007/07/01 CRDT- 2006/12/22 09:00 PHST- 2006/12/22 09:00 [pubmed] PHST- 2007/04/05 09:00 [medline] PHST- 2006/12/22 09:00 [entrez] PHST- 2007/07/01 00:00 [pmc-release] AID - JVI.02245-06 [pii] AID - 2245-06 [pii] AID - 10.1128/JVI.02245-06 [doi] PST - ppublish SO - J Virol. 2007 Mar;81(6):2675-87. doi: 10.1128/JVI.02245-06. Epub 2006 Dec 20.