Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies

Shimamoto, Chie; Ohnishi, Tetsuo; Maekawa, Motoko; Watanabe, Akïharu; Ohba, Hideki; Arai, Ryoichi; Iwayama, Yoshimi; Hisano, Yu; Toyota, Tomoko; Toyoshima, Manabu; Suzuki, Katsuaki; Shirayama, Yukihiko; Nakamura, Kazuhiko; Mori, Norio; Owada, Yuji; Kobayashi, Tetsuyuki; Yoshikawa, Takeo

doi:10.1093/hmg/ddu369

Cited by 94 publications

(67 citation statements)

References 73 publications

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“…Interestingly, this selective impairment of social novelty preference has been reported across a broad range of animal models of schizophrenia (Kaminitz et al 2014; O'Tuathaigh et al 2007; Shimamoto et al 2014; Zoubovsky et al 2015, but O'Tuathaigh et al 2010a). Eagle and co-workers (Eagle et al 2013) proposed that this selective impairment might be related to the differences between sensation-seeking versus novelty-seeking behaviors, the latter requiring to recall and recognize a familiar versus a novel object.…”

Section: Discussionmentioning

confidence: 77%

Disruption of social cognition in the sub-chronic PCP rat model of schizophrenia: Possible involvement of the endocannabinoid system

Seillier

Giuffrida

2016

European Neuropsychopharmacology

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Previous studies have shown that social withdrawal in the phencyclidine (PCP) rat model of schizophrenia results from deficient endocannabinoid-induced activation of CB1 receptors. To understand the underlying cognitive mechanisms of the social deficit in PCP-treated rats, we examined the impact of pharmacological manipulation of the endocannabinoid system on sociability (i.e. social approach) and social novelty preference (which relies on social recognition). Control rats showed a clear preference for a “social” cage (i.e. unfamiliar stimulus rat placed under a wire mesh cage) versus an “empty” cage, and spent more time exploring a “novel” cage (i.e. new stimulus rat) versus a “familiar” cage. In contrast, rats receiving PCP (5 mg/kg, b.i.d. for 7 days, followed by a 7 day-washout period) showed intact sociability, but lacked social novelty preference. This PCP-induced deficit was due to increased activity at CB1 receptors as it was reversed by systemic administration of the CB1 antagonist AM251 (1 mg/kg). In agreement with this hypothesis, the cannabinoid agonist CP55,940 (0.003 – 0.03 mg/kg) dose-dependently suppressed social novelty preference in control animals without affecting sociability. Taken together, these data suggest that PCP-treated rats have a deficit in social cognition, possibly induced by increased stimulation of CB1 receptors. This deficit, however, is distinct from the social withdrawal previously observed in these animals, as the latter is due to deficient, rather than increased, CB1 stimulation.

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Section: Discussionmentioning

confidence: 77%

Disruption of social cognition in the sub-chronic PCP rat model of schizophrenia: Possible involvement of the endocannabinoid system

Seillier

Giuffrida

2016

European Neuropsychopharmacology

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“…We recently reported hyperactivity and anxiety‐related phenotypes in Fabp7 KO mice (Shimamoto et al, ). Consistently, here we found that total distance traveled (1,526 ± 113 cm in WT vs. 2,720 ± 107 cm in KO, P < 0.001; Fig.…”

Section: Resultsmentioning

confidence: 97%

Astrocyte‐expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons

Ebrahimi

Yamamoto

Sharifi

et al. 2015

Glia

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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.

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“…Interestingly, gene expression of FABP3, FABP5, and FABP7 has been shown to be modulated in psychiatric illnesses such as schizophrenia and ASD [154]. In the brains of ASD patients, FABP7, which binds DHA preferentially, was upregulated in both the frontal and parietal cortex [155]. As in schizophrenic patients, PUFA distribution and metabolism are markedly altered in ASD patients.…”

Section: Risk Factors For Neuroinflammation and Autismmentioning

confidence: 99%

Neuroinflammation in Autism: Plausible Role of Maternal Inflammation, Dietary Omega 3, and Microbiota

et al. 2016

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Several genetic causes of autism spectrum disorder (ASD) have been identified. However, more recent work has highlighted that certain environmental exposures early in life may also account for some cases of autism. Environmental insults during pregnancy, such as infection or malnutrition, seem to dramatically impact brain development. Maternal viral or bacterial infections have been characterized as disruptors of brain shaping, even if their underlying mechanisms are not yet fully understood. Poor nutritional diversity, as well as nutrient deficiency, is strongly associated with neurodevelopmental disorders in children. For instance, imbalanced levels of essential fatty acids, and especially polyunsaturated fatty acids (PUFAs), are observed in patients with ASD and other neurodevelopmental disorders (e.g., attention deficit hyperactivity disorder (ADHD) and schizophrenia). Interestingly, PUFAs, and specifically n-3 PUFAs, are powerful immunomodulators that exert anti-inflammatory properties. These prenatal dietary and immunologic factors not only impact the fetal brain, but also affect the microbiota. Recent work suggests that the microbiota could be the missing link between environmental insults in prenatal life and future neurodevelopmental disorders. As both nutrition and inflammation can massively affect the microbiota, we discuss here how understanding the crosstalk between these three actors could provide a promising framework to better elucidate ASD etiology.

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Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies

Cited by 94 publications

References 73 publications

Disruption of social cognition in the sub-chronic PCP rat model of schizophrenia: Possible involvement of the endocannabinoid system

Disruption of social cognition in the sub-chronic PCP rat model of schizophrenia: Possible involvement of the endocannabinoid system

Astrocyte‐expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons

Neuroinflammation in Autism: Plausible Role of Maternal Inflammation, Dietary Omega 3, and Microbiota

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