Metallothioneins and zinc dysregulation contribute to neurodevelopmental damage in a model of perinatal viral infection.

Brain Pathology
B L WilliamsW I Lipkin

Abstract

Neonatal Borna disease (NBD) virus infection in the Lewis rat results in life-long viral persistence and causes behavioral and neurodevelopmental abnormalities. A hallmark of the disorder is progressive loss of cerebellar Purkinje and dentate gyrus granule cells. Findings of increased brain metallothionein-I and -II (MT-I/-II) mRNA expression in cDNA microarray experiments led us to investigate MT isoforms and their relationship to brain zinc metabolism, cellular toxicity, and neurodevelopmental abnormalities in this model. Real-time PCR confirmed marked induction of MT-I/-II mRNA expression in the brains of NBD rats (40.5-fold increase in cerebellum, p<0.0001; 6.8-fold increase in hippocampus, p=0.003; and 9.5-fold increase in striatum, p=0.0012), whereas a trend toward decreased MT-III mRNA was found in hippocampus (1.25-fold decrease, p=0.0841). Double label immunofluorescence revealed prominent MT-I/-II expression in astrocytes throughout the brain; MT-III protein was decreased in granule cell neurons and increased in astrocytes, with differential subcellular distribution from cytoplasmic to nuclear compartments in NBD rat hippocampus. Modified Timm staining of hippocampus revealed reduced zinc in mossy fiber projections to...Continue Reading

References

Jan 1, 1989·International Review of Neurobiology·C J Frederickson
Feb 20, 1989·Brain Research·C J FredericksonJ F McGinty
Nov 21, 1986·Neuroscience Letters·M YokoyamaD W Choi
Feb 1, 1985·Molecular and Cellular Biology·M K Yagle, R D Palmiter
Jan 1, 1994·Brain Research. Brain Research Reviews·M R Celio, I Blümcke
Apr 1, 1993·The European Journal of Neuroscience·E S WintergerstU Bartsch
Oct 1, 1993·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·L Mucke, M Eddleston
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·R D PalmiterS D Findley
Feb 1, 1997·Toxicology and Applied Pharmacology·M AschnerA I Bush
Nov 14, 1997·Brain Research. Developmental Brain Research·J SawashitaS Okada
Nov 14, 1997·Proceedings of the National Academy of Sciences of the United States of America·H J WenzelR D Palmiter
Jan 1, 1997·Neurobiology of Disease·M P Cuajungco, G J Lees
Apr 8, 1998·Annual Review of Neuroscience·D W Choi, J Y Koh
Jul 11, 1998·Molecular Pharmacology·R J VandenbergG A Johnston
Oct 7, 1998·The Journal of Toxicological Sciences·C D Klaassen, J Liu
Feb 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·T B ColeR D Palmiter
Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·M HornigW I Lipkin
Mar 23, 2000·Journal of Virology·D Gonzalez-DuniaJ C De La Torre
Dec 13, 2000·Brain Research. Brain Research Reviews·A Takeda
Jul 27, 2001·Brain Research Bulletin·J HidalgoM Vasák
Aug 10, 2001·Current Opinion in Microbiology·K M CarboneM V Pletnikov
Nov 24, 2001·Brain Research. Developmental Brain Research·Y SogawaG L Holmes
May 3, 2002·Nature·Hongjun SongFred H Gage
May 23, 2002·Cellular and Molecular Life Sciences : CMLS·P CoyleA M Rofe
Oct 18, 2002·Biochimica Et Biophysica Acta·Ho Jin YouHye Gwang Jeong
May 22, 2003·Neurobiology of Disease·Javier CarrascoJuan Hidalgo

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Citations

Jan 7, 2014·Neurochemistry International·Sushil Sharma, Manuchair Ebadi
Jan 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yuan-Ju WuMartin Schwemmle
May 22, 2010·Interdisciplinary Perspectives on Infectious Diseases·Marco Bortolato, Sean C Godar
Mar 6, 2010·Interdisciplinary Perspectives on Infectious Diseases·Marylou V Solbrig

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