The Effects of Fabp7 and Fabp5 on Postnatal Hippocampal Neurogenesis in the Mouse

Abstract

New neurons are continually produced after birth from neural stem/progenitor cells (NSCs/NPCs) in the hippocampal dentate gyrus (DG). Recent studies have reported that fatty acid binding protein 7 (Fabp7/brain lipid binding protein (BLBP)) is required for the maintenance of embryonic NSCs/NPCs and have identified an association between the Fabp7 gene and behavioral paradigms that correlate with hippocampal functions. However, the specific roles of Fabps in postnatal neurogenesis remain unknown. Herein, we demonstrate the effects of Fabp7, and another Fabp, Fabp5, on postnatal neurogenesis. Fabp7 and Fabp5 were detected in the subgranular zone (SGZ) of the DG, and Fabp7+ cells were less differentiated than Fabp5+ cells. We analyzed the differentiation state of NSCs/NPCs in the SGZ of 4-week-old (4w) Fabp7 knockout (7KO), Fabp5 KO (5KO), and Fabp7/Fabp5 double KO (7/5KO) mice and found that the number of NSCs/NPCs was dramatically reduced compared with wild-type mice. Although the uptake of BrdU 1 day after injection was decreased in all KO mice, the survival of BrdU+ cells 1 month after injection was increased in the 7/5KO mice compared to other three genotypes. We also observed an enhancement of neuronal differentiation in all Fabp KO mice. In addition, the proliferation and survival of NSCs/NPCs differed along the anterior-posterior axis (A-P axis). A greater number of newborn cells in the posterior region became extinct, but this tendency was not apparent in the Fabps KO mice. These data suggest that Fabp7 and Fabp5 have differential roles for proliferation and survival of the NSCs/NPCs during postnatal DG neurogenesis.

Conserved molecular signatures of neurogenesis in the hippocampal subgranular zone of rodents and primates

“…Several such genes have previously been associated with adult neurogenesis and are likely to label salient cells associated with neurogenic processes, including specialized astrocyte/progenitor populations, e.g. radial cells [Fabp7 (Matsumata et al, 2012)], late stage neural progenitors, and immature granule neurons [Calb2 (Brandt et al, 2003), Neurod1 (Gao et al, 2009;Roybon et al, 2009), Stmn2 (Camoletto et al, 2001)]. …”

“…As an additional example, knockout of the genes encoding fatty acid binding proteins 5 and 7 (Fabp5/7) produces a dramatic reduction in neural progenitor cells and enhanced neuronal differentiation in the mouse SGZ (Matsumata et al, 2012). Interestingly, a few of these genes have previously been associated with neurogenesis in the SVZ, but not thus far in the SGZ.…”

Fatty Acid-binding Protein 5 (FABP5) Regulates Cognitive Function Both by Decreasing Anandamide Levels and by Activating the Nuclear Receptor Peroxisome Proliferator-activated Receptor β/δ (PPARβ/δ) in the Brain

“…The intracellular lipid-binding protein (iLBP) 3 termed fatty acid-binding protein 5 (FABP5) is expressed during neurogenesis and in mature neurons in most regions of the brain (1)(2)(3). However, the nature of its role(s) in the brain and the exact CNS function(s) that rely on FABP5 are poorly understood.…”

FABP5 (fatty acid binding protein 5 (psoriasis-associated))

“…FABP5 transcripts are detected in mid-term embryonic rat brain, peaking at birth and gradually decreasing from P1 to P21, with expression virtually undetectable in the adult brain (Owada et al, 2002), except during regeneration in response to neuronal injury (Allen et al, 2001). FABP5 is critical in postnatal hippocampal dentate gyrus neurogenesis in mice (Matsumata et al, 2012).…”

“…Nuclear localization upon binding to linoleic acid and AA is thought to influence gene expression through activation of the nuclear receptor PPARβ/δ (Tan et al, 2001), which controls the expression of genes involved in lipid and glucose metabolism, differentiation, and survival (Schug et al, 2007). FABP5 expression during development is associated with neurite outgrowth (Allen et al, 2001), with an important role in post-natal hippocampal dentate gyrus neurogenesis through nuclear transport of RA to activate PPARβ/δ (Matsumata et al, 2012). The hippocampi of FABP5-null mice contain excess neuronal progenitors and are deficient in mature neurons (Yu et al, 2012).…”