Schizophrenia-Like Behavioral Impairments in Mice with Suppressed Expression of Piccolo in the Medial Prefrontal Cortex
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- Atsumi Nitta
- Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
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- Naotaka Izuo
- Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
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- Kohei Hamatani
- Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
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- Ryo Inagaki
- Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
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- Yuka Kusui
- Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
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- Kequan Fu
- Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
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- Takashi Asano
- Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
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- Youta Torii
- Department of Psychiatry, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan
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- Chikako Habuchi
- Department of Psychiatry, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan
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- Hirotaka Sekiguchi
- Department of Psychiatry, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan
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- Shuji Iritani
- Department of Psychiatry, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan
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- Shin-ichi Muramatsu
- Open Innovation Center, Division of Neurological Gene Therapy, Jichi Medical University, Shimotsuke 329-0498, Japan
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- Norio Ozaki
- Department of Psychiatry, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan
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- Yoshiaki Miyamoto
- Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
説明
<jats:p>Piccolo, a presynaptic cytomatrix protein, plays a role in synaptic vesicle trafficking in the presynaptic active zone. Certain single-nucleotide polymorphisms of the Piccolo-encoding gene PCLO are reported to be associated with mental disorders. However, a few studies have evaluated the relationship between Piccolo dysfunction and psychotic symptoms. Therefore, we investigated the neurophysiological and behavioral phenotypes in mice with Piccolo suppression in the medial prefrontal cortex (mPFC). Downregulation of Piccolo in the mPFC reduced regional synaptic proteins, accompanied with electrophysiological impairments. The Piccolo-suppressed mice showed an enhanced locomotor activity, impaired auditory prepulse inhibition, and cognitive dysfunction. These abnormal behaviors were partially ameliorated by the antipsychotic drug risperidone. Piccolo-suppressed mice received mild social defeat stress showed additional behavioral despair. Furthermore, the responses of these mice to extracellular glutamate and dopamine levels induced by the optical activation of mPFC projection in the dorsal striatum (dSTR) were inhibited. Similarly, the Piccolo-suppressed mice showed decreased depolarization-evoked glutamate and -aminobutyric acid elevations and increased depolarization-evoked dopamine elevation in the dSTR. These suggest that Piccolo regulates neurotransmission at the synaptic terminal of the projection site. Reduced neuronal connectivity in the mPFC-dSTR pathway via suppression of Piccolo in the mPFC may induce behavioral impairments observed in schizophrenia.</jats:p>
収録刊行物
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- Journal of Personalized Medicine
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Journal of Personalized Medicine 11 (7), 607-, 2021-06-26
MDPI AG