Spatio-temporally differential expression of genes for three members of fatty acid binding proteins in developing and mature rat brains

doi:10.1016/S0891-0618(96)00192-5

Journal of Chemical Neuroanatomy

Volume 12, Issue 2, December 1996, Pages 113-122

https://doi.org/10.1016/S0891-0618(96)00192-5 Get rights and content

Abstract

The chronological changes in the gene expression for three species of cytosolic fatty acid-binding proteins (FABPs) in the rat brain were examined by Northern and in situ hybridization analyses. The expression for heart(H)-FABP became evident after birth, with a gradual increase and confined to the gray matter, suggesting that the expression of H-FABP mRNA is neuron-specific in postnatal brain. The expression for brain(B)-FABP was very intense in the ventricular germinal zone, without expression in the cerebellar external granule cell layer, suggesting the dominant expression in the cells of glial lineage. B-FABP mRNA was transiently expressed in perinatal gray as well as white matter and the expression in glial cells persists only in the olfactory nerve fiber layer at the adult stage. On the other hand, the expression for skin type(S)-FABP was evident in the both ventricular germinal zone and cerebellar external granule cell layer, suggesting the expression in cells of neuronal lineage. The expression for S-FABP was evident in the prenatal gray matter and S-FABP mRNA was expressed in glial cells at early postnatal stage, whereafter the expression decreased to, but remained at weak levels in the adult brain. Discrete functions of the three FABPs were suggested in neurons and glia differentially at various developmental stages.

References (31)

D.M. Araujo et al.
Insulin-like growth factor 1 (somatomedin C) receptors in the rat brain: distribution and interaction with the hippocampal cholinergic system
Brain Res.
(1989)
T. Borchers et al.
Fatty acid binding proteins
Curr. Topics Membranes
(1994)
L. Feng et al.
Brain lipid-binding protein (BLBP): a novel signaling system in the developing mammalian CNS
Neuron
(1994)
J.F. Glatz et al.
Cytoplasmic fatty acid binding protein: significance for intracellular transport of fatty acids and putative role on signal transduction pathways
Prostaglandins Leukotrienes Essent. Fatty Acids
(1993)
J.I. Gordon et al.
The nucleotide sequence of rat liver fatty acid binding protein mRNA
J. Biol. Chem.
(1983)
P. Madsen et al.
Molecular cloning and expression of a novel keratinocyte protein (psoriasis-associated fatty acid-binding protein [PA-FABP]) that is highly up-regulated in psoriatic skin and that shares similarity to fatty acid-binding proteins
J. Invest. Dermatol.
(1992)
J.C. Sacchettini et al.
Rat heart fatty acid-binding protein is highly homologous to the murine adipocyte 422 protein and the P2 protein of peripheral nerve myelin
J. Biol. Chem.
(1986)
P.A. Sellner et al.
Developmental role of fatty acid-binding proteins in mouse brain
Dev. Brain Res.
(1995)
M. Senjo et al.
Isolation and characterization of fatty acid-binding protein from rat brain
Arch. Biochem. Biophys.
(1985)
M. Treuner et al.
Cloning and characterization of the mouse gene encoding mammary derived growth inhibitor/heart-fatty acid-binding protein
Gene
(1994)

J.H. Veerkamp et al.

Structural and functional features of different typees of cytoplasmic fatty acid binding proteins

Biochim. Biophys. Acta

(1991)

A. Wanaka et al.

Developmental study of nerve growth-factor receptor mRNA expression in the postnatal rat cerebellum

Dev. Brain Res.

(1990)

M. Watanabe et al.

Ontogenic changes in the expression of neuron-specific enolase (NSE) and its mRNA in the Purkinje cells of the rat cerebellum: Immunohistochemical and in situ hybridization study

Dev. Brain Res.

(1990)

R. Watanabe et al.

Molecular cloning of a cDNA encoding a novel fatty acid-binding protein from rat skin

Biochem. Biophys. Res. Commun.

(1994)

D.H. Alpers et al.

Cloning of a cDNA encoding rat intestinal fatty acid binding protein

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Spatio-temporally differential expression of genes for three members of fatty acid binding proteins in developing and mature rat brains

Abstract

Brain Res.

Curr. Topics Membranes

Neuron

Prostaglandins Leukotrienes Essent. Fatty Acids

J. Biol. Chem.

J. Invest. Dermatol.

J. Biol. Chem.

Dev. Brain Res.

Arch. Biochem. Biophys.

Gene

Biochim. Biophys. Acta

Dev. Brain Res.

Dev. Brain Res.

Biochem. Biophys. Res. Commun.

Cloning of a cDNA encoding rat intestinal fatty acid binding protein