Residual benzodiazepine (BZ) binding in the cortex of pcd mutant cerebella and qualitative BZ binding in the deep cerebellar nuclei of control and mutant mice: an autoradiographic study

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Abstract

In mutant mice 'Purkinje cell degeneration' (pcd), there is an almost complete degeneration of Purkinje cells followed subsequently by a partial degeneration of granule cells. Recent neurochemical studies have revealed a 50% decrease in benzodiazepine (BZ) receptors in 45-day-old pcd mutants after degeneration of the Purkinje cells. At 300 days there is an 80% decrease in BZ receptors concomitant with granule cell losses. To determine the histological localization of these receptor changes this autoradiographic analysis was conducted. An in vitro autoradiographic technique was used to explore [3H]flunitrazepam binding. BZ receptors were found to be more concentrated in the molecular than the granular layer of mutant and control cerebellar cortices. There was, nonetheless, no statistically significant difference in grain counts between control and mutant mice in any layer. Substantial atrophy of cerebellar structures, particularly of the molecular layer, occurred in the mutant mice. It began even before 45 days of age but was extreme at 300 days. When the appropriate mathematical correction factor was introduced for the layer atrophy there was a 60% decrease in grain count in 45-day-old mutants in the molecular layer and a 84% decrease in 300-day-old mutants compared to controls. The initial decrease in total BZ receptors in the 45-day-old mutant animals is associated with a selective loss of Purkinje cells. The amount of receptor binding which persists in the 300-day-old mutants in the molecular layer would appear to reflect binding in the remaining parallel fibers from granule cells which remain. Because there is a significant decrease in the granular layer width especially in the 300-day-old mutant animals, it is proposed that other cerebellar elements present in this layer may contain BZ receptors. An unexpected finding was the substantial BZ binding in the deep cerebellar nuclei both of 45- and 300-day-old animals whether mutant or control. The density of such binding is greater in the nuclei of the mutant mice. The possibility that this receptor binding alteration may reflect a supersensitivity phenomenon is raised. Since there is complete interruption of axonal input to the deep nuclei from the Purkinje cells, particularly at 300 days, additional studies must be conducted to identify the structures accounting for the substantial residual binding in these nuclei.

Original languageEnglish (US)
Pages (from-to)70-78
Number of pages9
JournalBrain research
Volume343
Issue number1
DOIs
StatePublished - Sep 16 1985

Keywords

  • autoradiography
  • benzodiazepine receptor
  • cerebellar cortex
  • cerebellum
  • deep cerebellar nuclei
  • granular layer
  • molecular layer
  • pcd mutant mouse
  • Purkinje cell layer

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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