Heterotypic sprouting of serotonergic forebrain fibers in the brindled mottled mutant mouse

Parthena Martin, Masaki Ohno, Stan B. Southerland, Richard B. Mailman, Kinuko Suzuki

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11 Scopus citations

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-β-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.

Original languageEnglish (US)
Pages (from-to)215-225
Number of pages11
JournalDevelopmental Brain Research
Volume77
Issue number2
DOIs
StatePublished - Feb 18 1994

All Science Journal Classification (ASJC) codes

  • Developmental Neuroscience
  • Developmental Biology

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