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Sapap4 deficiency leads to postsynaptic defects and abnormal behaviors relevant to hyperkinetic neuropsychiatric disorder in mice.
Wang, Tianhua; Bai, Yunxia; Zheng, Xianjie; Liu, Xinxia; Xing, Shuang; Wang, Linbin; Wang, Huimin; Feng, Guoping; Li, Chunxia.
Afiliação
  • Wang T; Key Laboratory of Brain Functional Genomics (STCSM & MOE), School of Psychology and Cognitive Science, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.
  • Bai Y; Key Laboratory of Brain Functional Genomics (STCSM & MOE), School of Psychology and Cognitive Science, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.
  • Zheng X; Key Laboratory of Brain Functional Genomics (STCSM & MOE), School of Psychology and Cognitive Science, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.
  • Liu X; Key Laboratory of Brain Functional Genomics (STCSM & MOE), School of Psychology and Cognitive Science, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.
  • Xing S; Key Laboratory of Brain Functional Genomics (STCSM & MOE), School of Psychology and Cognitive Science, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.
  • Wang L; Key Laboratory of Brain Functional Genomics (STCSM & MOE), School of Psychology and Cognitive Science, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.
  • Wang H; Key Laboratory of Brain Functional Genomics (STCSM & MOE), School of Psychology and Cognitive Science, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.
  • Feng G; NYU-ECNU Institute of Brain and Cognitive Science at NYU Shanghai, 3663 North Zhongshan Road, Shanghai, 200062, China.
  • Li C; McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar Street, Cambridge, Massachusetts, 02139, USA.
Cereb Cortex ; 33(4): 1104-1118, 2023 02 07.
Article em En | MEDLINE | ID: mdl-35368073
Postsynaptic proteins play critical roles in synaptic development, function, and plasticity. Dysfunction of postsynaptic proteins is strongly linked to neurodevelopmental and psychiatric disorders. SAP90/PSD95-associated protein 4 (SAPAP4; also known as DLGAP4) is a key component of the PSD95-SAPAP-SHANK excitatory postsynaptic scaffolding complex, which plays important roles at synapses. However, the exact function of the SAPAP4 protein in the brain is poorly understood. Here, we report that Sapap4 knockout (KO) mice have reduced spine density in the prefrontal cortex and abnormal compositions of key postsynaptic proteins in the postsynaptic density (PSD) including reduced PSD95, GluR1, and GluR2 as well as increased SHANK3. These synaptic defects are accompanied by a cluster of abnormal behaviors including hyperactivity, impulsivity, reduced despair/depression-like behavior, hypersensitivity to low dose of amphetamine, memory deficits, and decreased prepulse inhibition, which are reminiscent of mania. Furthermore, the hyperactivity of Sapap4 KO mice could be partially rescued by valproate, a mood stabilizer used for mania treatment in humans. Together, our findings provide evidence that SAPAP4 plays an important role at synapses and reinforce the view that dysfunction of the postsynaptic scaffolding protein SAPAP4 may contribute to the pathogenesis of hyperkinetic neuropsychiatric disorder.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Mania / Proteínas do Tecido Nervoso Limite: Animals / Humans Idioma: En Revista: Cereb Cortex Assunto da revista: CEREBRO Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Mania / Proteínas do Tecido Nervoso Limite: Animals / Humans Idioma: En Revista: Cereb Cortex Assunto da revista: CEREBRO Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China