Dataset Information

Ceruloplasmin gene expression in the murine central nervous system.

ABSTRACT: Aceruloplasminemia is an autosomal recessive disorder resulting in neurodegeneration of the retina and basal ganglia in association with iron accumulation in these tissues. To begin to define the mechanisms of central nervous system iron accumulation and neuronal loss in this disease, cDNA clones encoding murine ceruloplasmin were isolated and characterized. RNA blot analysis using these clones detected a 3.7-kb ceruloplasmin-specific transcript in multiple murine tissues including the eye and several regions of the brain. In situ hybridization of systemic tissues revealed cell-specific ceruloplasmin gene expression in hepatocytes, the splenic reticuloendothelial system and the bronchiolar epithelium of the lung. In the central nervous system, abundant ceruloplasmin gene expression was detected in specific populations of astrocytes within the retina and the brain as well as the epithelium of the choroid plexus. Analysis of primary cell cultures confirmed that astrocytes expressed ceruloplasmin mRNA and biosynthetic studies revealed synthesis and secretion of ceruloplasmin by these cells. Taken together these results demonstrate abundant cell-specific ceruloplasmin expression within the central nervous system which may account for the unique clinical and pathologic findings observed in patients with aceruloplasminemia.

SUBMITTER: Klomp LW

PROVIDER: S-EPMC507418 | biostudies-other | 1996 Jul

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Ceruloplasmin gene expression in the murine central nervous system.

Klomp L W LW Farhangrazi Z S ZS Dugan L L LL Gitlin J D JD

The Journal of clinical investigation 19960701 1

Aceruloplasminemia is an autosomal recessive disorder resulting in neurodegeneration of the retina and basal ganglia in association with iron accumulation in these tissues. To begin to define the mechanisms of central nervous system iron accumulation and neuronal loss in this disease, cDNA clones encoding murine ceruloplasmin were isolated and characterized. RNA blot analysis using these clones detected a 3.7-kb ceruloplasmin-specific transcript in multiple murine tissues including the eye and s ...[more]

PMID: 8690795

Similar Datasets

Project description:BackgroundFolates are a family of B9 vitamins that serve as one-carbon donors critical to biosynthetic processes required for the development and function of the central nervous system (CNS) in mammals. Folate transport is mediated by three highly specific systems: (1) folate receptor alpha (FRα; FOLR1/Folr1), (2) the reduced folate-carrier (RFC; SLC19A1/Slc19a1) and (3) the proton-coupled folate transporter (PCFT; SLC46A1/Slc46a1). Folate transport into and out of the CNS occurs at the blood-cerebrospinal fluid barrier (BCSFB), mediated by FRα and PCFT. Impairment of folate transport at the BCSFB results in cerebral folate deficiency in infants characterized by severe neurological deficiencies and seizures. In contrast to the BCSFB, CNS folate transport at other brain barriers and brain parenchymal cells has not been extensively investigated. The aim of this study is to characterize folate transport systems in the murine CNS at several known barriers encompassing the BCSFB, arachnoid barrier (AB), blood-brain barrier (BBB) and parenchymal cells (astrocytes, microglia, neurons).MethodsApplying immunohistochemistry, localization of folate transport systems (RFC, PCFT, FRα) was examined at CNS barriers and parenchymal sites in wildtype (C57BL6/N) mice. Subcellular localization of the folate transport systems was further assessed in an in vitro model of the mouse AB. Gene and protein expression was analyzed in several in vitro models of brain barriers and parenchyma by qPCR and western blot analysis.ResultsRFC, PCFT, and FRα expression was localized within the BCSFB and BBB consistent with previous reports. Only RFC and PCFT expression was detected at the AB. Varied levels of RFC and PCFT expression were detected in neuronal and glial cells.ConclusionsLocalization of RFC and PCFT within the AB, described here for the first time, suggest that AB may contribute to folate transport between the peripheral circulation and the CSF. RFC and PCFT expression observed in astrocytes and microglia is consistent with the role that one or both of these transporters may play in delivering folates into cells within brain parenchyma. These studies provide insights into mechanisms of folate transport in the CNS and may enhance our understanding of the critical role folates play in neurodevelopment and in the development of novel treatment strategies for disorders of brain folate deficiency due to impaired transporter function.

Dataset Information

Ceruloplasmin gene expression in the murine central nervous system.

Publications

Ceruloplasmin gene expression in the murine central nervous system.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets