Altered emotional behavioral responses in mice lacking brain‐type fatty acid‐binding protein gene

Abstract

Brain-type fatty acid-binding protein (B-FABP) belongs to a family of intracellular lipid-binding proteins. B-FABP exhibits a binding affinity to long-chain fatty acids (FAs) whose effects on brain functions including development, emotion, learning and memory have been proposed. B-FABP is localized in the ventricular germinal cells in embryonic brain and astrocytes in developing and mature brain of rodents. In the present study we generated the mouse harboring a null mutation in the B-FABP gene and studied its phenotype. B-FABP mutant mice exhibited the enhanced anxiety and increased fear memory as well as the decreased content of docosahexaenoic acid (DHA) in their brain during the neonatal period without detection of any histological changes in the brain. In the adult brain, B-FABP was localized more numerously to the astrocytes in the amygdala and septal area than to those in the hippocampal area. Analysis of FA content in the amygdala of adult brain revealed that arachidonic and palmitic acids increased significantly in the mutant mice compared with wild-type. Furthermore, the response of N-methyl-d-aspartate receptor-mediated current to DHA in isolated neurons from B-FABP mutant brain was significantly decreased compared with that of wild-type, while no significant differences were detected in behavioral responses related to the spatial learning/memory or in the hippocampal long-term potentiation. These data indicate that B-FABP is crucially involved in the fear memory and anxiety through its binding with FAs and/or its own direct effects on pertinent metabolism/signaling of FAs.

Identification of intracellular carriers for the endocannabinoid anandamide

“…To confirm that these proteins constitute the endogenous repertoire of FABPs in N18TG2 cells, we performed RT-PCR analysis in N18TG2 cells and mouse brain as a control. As expected, and in accordance with previous data (44,45), FABP3, FABP5, and FABP7 were expressed in brain (Fig. 3E).…”

The Neurogenesis-Controlling Factor, Pax6, Inhibits Proliferation and Promotes Maturation in Murine Astrocytes

“…The sections were washed with PBS three times, incubated with Alexa Fluor 488 or 555 (Invitrogen, Carlsbad, CA) for 1 h at room temperature, washed, and mounted on slide glass. Antibodies against GLAST and fatty-acidbinding protein 7 (FABP7) were kind gifts from Dr. Masahiko Watanabe (Hokkaido University, Sapporo, Japan) (Iwanaga et al, 2005) and Dr. Yuji Owada (Yamaguchi University, Yamaguchi, Japan) (Owada et al, 2006), respectively. BrdU labeling analyses.…”

“…5 B, C). BrdU ϩ cells were observed throughout the spinal cord at E14.5, E16.5, and E18.5, with most cells coexpressing FABP7 [brain lipid binding protein (BLBP)], a marker for astrocytic progenitors and mature astrocytes (Barry and McDermott, 2005;Owada et al, 2006) (Fig. 5B).…”

Heart-Type Fatty Acid Binding Protein Regulates Dopamine D2Receptor Function in Mouse Brain

“…B-FABP knockdown by small interfering RNA impairs cell proliferation and promotes neuronal differentiation in cortical neuroepithelial cells (Arai et al, 2005). B-FABP knock-out (KO) mice show abnormalities in emotional behavior (Owada et al, 2006), decreased neurogenesis in the dentate gyrus, and impaired prepulse inhibition (Watanabe et al, 2007). H-FABP KO mice also exhibit a 24% reduction in incorporation of […”