Metallothioneins and Zinc Dysregulation Contribute to Neurodevelopmental Damage in a Model of Perinatal Viral Infection

• Published in: Brain pathology (Zurich, Switzerland) Switzerland), 2006-01, Vol.16 (1), p.1-14
• Main Authors: Williams, Brent L., Yaddanapudi, Kavitha, Kirk, Cassandra M., Soman, Arya, Hornig, Mady, Lipkin, W. Ian
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes - drug effects; Astrocytes - metabolism; Blotting, Western; Borna Disease - metabolism; Borna Disease - pathology; Borna disease virus; Extracellular Matrix Proteins - biosynthesis; Extracellular Matrix Proteins - genetics; Fluorescent Antibody Technique; Metallothionein - physiology; Mossy Fibers, Hippocampal - drug effects; Mossy Fibers, Hippocampal - metabolism; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Neurodegenerative Diseases - etiology; Neurodegenerative Diseases - pathology; Neurodegenerative Diseases - virology; Neurons - drug effects; Neurons - metabolism; Oligonucleotide Array Sequence Analysis; Rats; Rats, Inbred Lew; Reverse Transcriptase Polymerase Chain Reaction; RNA - biosynthesis; RNA - isolation & purification; Zinc - metabolism
• ISSN: 1015-6305; 1750-3639
• DOI: 10.1111/j.1750-3639.2006.tb00556.x

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