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Gene Expression Profiling in the Cortex of Fabp4 Knockout Mice.

Hinako Kirikae1, Xiaofeng He1, Tetsuo Ohnishi2

  • 1Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan.

Neuropsychopharmacology Reports
|February 8, 2025
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Summary

Fatty acid binding protein 4 (Fabp4) is not found in the brain, but its absence alters brain gene expression. This suggests systemic lipid metabolism influences neurodevelopment and disorders like autism spectrum disorder (ASD).

Keywords:
Fabp4 knockout (KO) miceRNA‐seqautism spectrum disorderepigenetic gene expressionsynaptic gene expression

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Area of Science:

  • Neuroscience
  • Metabolic Regulation
  • Epigenetics

Background:

  • Fatty acid binding protein 4 (Fabp4) is crucial for peripheral lipid metabolism.
  • Its role in brain function is largely unknown.
  • Fabp4 knockout (KO) mice exhibit autism-like behaviors.

Purpose of the Study:

  • Investigate Fabp4 expression in the adult mouse brain.
  • Analyze gene expression changes in Fabp4 KO mice to understand its impact on brain function.

Main Methods:

  • In situ hybridization to detect Fabp4 expression in mouse brain regions.
  • RNA-sequencing (RNA-seq) for differential gene expression analysis in the prefrontal cortex of Fabp4 KO mice.

Main Results:

  • Fabp4 expression was undetectable in the adult mouse brain.
  • Fabp4 deficiency led to significant gene expression changes: 31 genes upregulated and 30 downregulated.
  • Downregulated genes involved histone methylation and metabolism; upregulated genes related to synaptic organization.

Conclusions:

  • Fabp4 is not directly expressed in the brain, but its deficiency impacts brain gene expression.
  • Peripheral metabolic pathways and epigenetic regulation likely mediate these effects.
  • Findings suggest systemic lipid metabolism influences neurodevelopmental disorders like ASD and highlight epigenetic mechanisms.