title: Astrocyte-expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons.
abstract: Fatty acid binding protein 7 (FABP7) expressed by astrocytes in developing and mature brains is involved in uptake and transportation of fatty acids, signal transduction, and gene transcription. Fabp7 knockout (Fabp7 KO) mice show behavioral phenotypes reminiscent of human neuropsychiatric disorders such as schizophrenia. However, direct evidence showing how FABP7 deficiency in astrocytes leads to altered brain function is lacking. Here, we examined neuronal dendritic morphology and synaptic plasticity in medial prefrontal cortex (mPFC) of Fabp7 KO mice and in primary cortical neuronal cultures. Golgi staining of cortical pyramidal neurons in Fabp7 KO mice revealed aberrant dendritic morphology and decreased spine density compared with those in wild-type (WT) mice. Aberrant dendritic morphology was also observed in primary cortical neurons co-cultured with FABP7-deficient astrocytes and neurons cultured in Fabp7 KO astrocyte-conditioned medium. Excitatory synapse number was decreased in mPFC of Fabp7 KO mice and in neurons co-cultured with Fabp7 KO astrocytes. Accordingly, whole-cell voltage-clamp recording in brain slices from pyramidal cells in the mPFC showed that both amplitude and frequency of action potential-independent miniature excitatory postsynaptic currents (mEPSCs) were decreased in Fabp7 KO mice. Moreover, transplantation of WT astrocytes into the mPFC of Fabp7 KO mice partially attenuated behavioral impairments. Collectively, these results suggest that astrocytic FABP7 is important for dendritic arbor growth, neuronal excitatory synapse formation, and synaptic transmission, and provide new insights linking FABP7, lipid homeostasis, and neuropsychiatric disorders, leading to novel therapeutic interventions.
authors: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Majid
authors: M
authors: Ebrahimi
authors: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Yui
authors: Y
authors: Yamamoto
authors: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Kazem
authors: K
authors: Sharifi
authors: Department of System Neuroscience, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Hiroyuki
authors: H
authors: Kida
authors: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Yoshiteru
authors: Y
authors: Kagawa
authors: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Yuki
authors: Y
authors: Yasumoto
authors: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Ariful
authors: A
authors: Islam
authors: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Hirofumi
authors: H
authors: Miyazaki
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Japan.
authors: Chie
authors: C
authors: Shimamoto
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Japan.
authors: Motoko
authors: M
authors: Maekawa
authors: Department of System Neuroscience, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Dai
authors: D
authors: Mitsushima
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Japan.
authors: Takeo
authors: T
authors: Yoshikawa
authors: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Yuji
authors: Y
authors: Owada
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology* / Q000637:transplantation; D018920:Coculture Techniques; D003712:Dendrites / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055369:Miniature Postsynaptic Potentials / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology* / Q000601:surgery; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
chemical_list: C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009419:Nerve Tissue Proteins
keywords: fatty acid binding protein; gene knockout mouse; glia; mEPSCs; mPFC