title: Heterotypic sprouting of serotonergic forebrain fibers in the brindled mottled mutant mouse.
abstract: The brindled mottled mouse has a mutation on the X-chromosome which causes alterations in copper metabolism. One role for copper is as a cofactor for dopamine-beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine (NE). This may explain the fact that the hemizygous males have low concentrations of NE, as well as high concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in the brainstem and forebrain. The present study quantified serotonin (5-HT) immunoreactive fibers in the cerebral cortex and striatum of hemizygous males and control littermates on postnatal (P) days 7, 10, 12 and 14. The density of 5-HT immunoreactive fibers was measured using a digitized imaging system in conjunction with darkfield microscopy. Measurements of 5-HT innervation showed an age-dependent increase in density of 5-HT immunoreactive fibers in all layers of the cerebral cortex, with fiber density in brindled mice approximately 70% greater than controls by P14. High performance liquid chromatography confirmed the increased concentrations of 5-HT and 5-HIAA, and the low concentration of NE, in several regions. We believe that these results are an example of heterotypic sprouting of 5-HT neurons, similar to that observed in neonatal rats given 6-hydroxydopamine (6-OHDA). If so, these data provide the first description of 5-HT heterotypic sprouting in mice, and the first description of 5-HT heterotypic sprouting resulting from a natural disease state, rather than an experimentally induced lesion.
authors.affiliation: Department of Pathology, University of North Carolina, Chapel Hill 27599.
authors.forename: P
authors.initials: P
authors.lastname: Martin
authors.forename: M
authors.initials: M
authors.lastname: Ohno
authors.forename: S B
authors.initials: SB
authors.lastname: Southerland
authors.forename: R B
authors.initials: RB
authors.lastname: Mailman
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009412:Nerve Fibers / Q000502:physiology*; D011247:Pregnancy; D016548:Prosencephalon / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D012701:Serotonin / Q000502:physiology*
chemical_list: D012701:Serotonin