Abstract

Brain fatty acid binding protein (Fabp7), which is important in early nervous system development, is expressed in astrocytes and neuronal cell precursors in mature brain. We report here that levels of Fabp7 mRNA in adult murine brain change over a 24 hour period. Unlike Fabp5, a fatty acid binding protein that is expressed widely in various cell types within brain, RNA analysis revealed that Fabp7 mRNA levels were elevated during the light period and lower during dark in brain regions involved in sleep and activity mechanisms. This pattern of Fabp7 mRNA expression was confirmed using in situ hybridization and found to occur throughout the entire brain. Changes in the intracellular distribution of Fabp7 mRNA were also evident over a 24 hour period. Diurnal changes in Fabp7, however, were not found in postnatal day 6 brain, when astrocytes are not yet mature. In contrast, granule cell precursors of the subgranular zone of adult hippocampus did undergo diurnal changes in Fabp7 expression. These changes paralleled oscillations in Fabp7 mRNA throughout the brain suggesting that cell-coordinated signals likely control brain-wide Fabp7 mRNA expression. Immunoblots revealed that Fabp7 protein levels also underwent diurnal changes in abundance, with peak levels occurring in the dark period. Of clock or clock-regulated genes, the synchronized, global cycling pattern of Fabp7 expression is unique and implicates glial cells in the response or modulation of activity and/or circadian rhythms.

Highlights

  • Brain fatty acid binding protein is a member of a large family of fatty acid binding proteins (Fabps) of relatively small molecular weight (,15 kD) that are expressed in a diverse set of vertebrate and invertebrate tissues [1]

  • To determine whether Fabp7 mRNA is diurnally expressed in other brain regions involved in activity, we examined the cycling of Fabp7 mRNA in the tuberomammilary nucleus (TMN), which contains histaminergic neurons thought to play a primary role in brain arousal [31,32,33], the pons, a brain area that has a broad role in activity states and the locus coeruleus (LC), which contains norepinephrine-releasing cells important in regulating sleep and activity [34]

  • This report describes the diurnal regulation of brain fatty acid binding protein (Fabp7) within astrocytes and subgranular zone precursors of the adult murine brain

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Summary

Introduction

Brain fatty acid binding protein ( known as brain lipid binding protein or Fabp7) is a member of a large family of fatty acid binding proteins (Fabps) of relatively small molecular weight (,15 kD) that are expressed in a diverse set of vertebrate and invertebrate tissues [1]. Fabps within brain are thought to govern the uptake and delivery of fatty acids like docosahexanoic acid (DHA) and arachadonic acid and to play important roles in cell differentiation [3,10,11]. The initial identification of Fabp established its presence within radial glia in embryonic brain and in neuronal cell progenitors in mature brain [3,12,13]. Most neuronal cell populations are thought to be derived from Fabp7-expressing progenitors [14]. Fabp mRNA levels were found to peak at birth and to undergo a dramatic reduction during early postnatal development, but to persist in radial glia-like neuronal progenitors and specific mature astrocyte populations [13]. An induction of Fabp increases the motility of glioma cells [18]

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