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The effects of Fabp7 and Fabp5 on postnatal hippocampal neurogenesis in the mouse
Miho Matsumata1, Nobuyuki Sakayori, Motoko Maekawa
1Division of Developmental Neuroscience, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University School of Medicine, Sendai, Japan.
Insights
Fatty acid binding proteins 7 and 5 (Fabp7 and Fabp5) are crucial for maintaining neural stem/progenitor cells (NSCs/NPCs) in the postnatal hippocampus. Their absence alters NSC/NPC proliferation, survival, and neuronal differentiation.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Neural stem/progenitor cells (NSCs/NPCs) generate new neurons in the adult hippocampus.
- Fatty acid binding protein 7 (Fabp7) is vital for embryonic NSCs/NPCs, with Fabp7 gene variants linked to hippocampal function.
- The role of fatty acid binding proteins (Fabps) in postnatal neurogenesis is not well understood.
Purpose of the Study:
- To investigate the roles of Fabp7 and Fabp5 in postnatal neurogenesis within the hippocampal dentate gyrus.
- To analyze the impact of Fabp7 and Fabp5 deficiency on NSC/NPC proliferation, survival, and differentiation.
Main Methods:
- Utilized knockout mouse models: Fabp7 KO (7KO), Fabp5 KO (5KO), and double KO (7/5KO).
- Assessed NSC/NPC populations in the subgranular zone (SGZ) of the dentate gyrus (DG).
- Employed Bromodeoxyuridine (BrdU) labeling to track cell proliferation and survival.
Main Results:
- Fabp7 and Fabp5 are expressed in the SGZ, with Fabp7+ cells showing less differentiation than Fabp5+ cells.
- NSC/NPC numbers were significantly reduced in all Fabp KO mice.
- While initial proliferation (BrdU uptake) decreased in KO mice, long-term survival of new cells increased in 7/5KO mice.
- Neuronal differentiation was enhanced in all Fabp KO groups.
- Fabp deficiency affected the anterior-posterior axis differences in cell proliferation and survival.
Conclusions:
- Fabp7 and Fabp5 play distinct roles in regulating the proliferation and survival of NSCs/NPCs during postnatal neurogenesis in the DG.
- These findings highlight the importance of Fabps in adult hippocampal neurogenesis and neuronal development.
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.
