Cytomegalovirus infection of the developing brain alters catecholamine and indoleamine metabolism.
Tissue concentrations of noradrenaline (NA), serotonin (5-HT), dopamine (DA) and selected metabolites were measured in the spinal cord, cerebellum, cerebral cortex and caudate-putamen of developing mice following intraventricular inoculation with murine cytomegalovirus (MCMV) on postnatal day 10. MCMV-infected animals exhibited transient signs of neurological impairment, including apparent hypertonicity of hindlimb extensors and abnormal gait, beginning on days 14-16 and continuing for 3-5 days. At the onset of neurological impairment, tissue concentrations of NA were significantly reduced in the spinal cord (20%), cerebellum (32%) and cerebral cortex (40%) of infected animals. Levels of 5-HT were significantly increased in the caudate-putamen (50%), while 5-hydroxyindoleacetic acid (5-HIAA) was increased in both the spinal cord (94%) and caudate-putamen (65%). The ratio of 5-HIAA/5-HT, which is frequently used as an estimate of turnover of 5-HT, was significantly increased in the spinal cord (90%) at the onset of neurological impairment. In the caudate-putamen of MCMV-infected animals, there were significant increases in the tissue levels of DA (37%), homovanillic acid (HVA, 41%) and 3,4-dihydroxyphenylacetic acid (DOPAC, 34%). All neurochemical parameters were normal in the MCMV-infected animals by postnatal day 70, approximately 50 days after the resolution of neurological signs. These results indicate transient alterations in monoamine metabolism in the developing nervous system during the pathogenesis of cytomegalovirus-induced movement and postural disorders.
O'Kusky
J R
JR
Department of Pathology, University of British Columbia, Vancouver, Canada.
Boyes
B E
BE
Walker
D G
DG
McGeer
E G
EG
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D001927:Brain Diseases / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007211:Indoles / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009638:Norepinephrine / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D012701:Serotonin / Q000502:physiology
D001679:Biogenic Amines; D002395:Catecholamines; D007211:Indoles; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D009638:Norepinephrine