High-Fat Diet Exacerbates Autistic-Like Restricted Repetitive Behaviors and Social Abnormalities in CC2D1A Conditional Knockout Mice

Yu Chiao Wang, Chin Hao Chen, Cheng Yi Yang, Pin Ling, Kuei Sen Hsu

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

Autism spectrum disorder (ASD) represents a heterogeneous group of neurodevelopmental disorders characterized by deficits in social communication, social interaction, and the presence of restricted repetitive behaviors. The cause of ASD involves complex interactions between genetic and environmental factors. Haploinsufficiency of the Coiled-coil and C2 domain containing 1A (Cc2d1a) gene is causally linked to ASD, and obesity has been associated with worse outcomes for ASD. High-fat diet (HFD) feeding leads to the development of obesity and metabolic dysfunction; however, the effect of HFD on pre-existing autistic-like phenotypes remains to be clarified. Here, we report that male Cc2d1a conditional knockout (cKO) mice fed with HFD, from weaning onwards and throughout the experimental period, show a marked aggravation in autistic-like phenotypes, manifested in increased restricted repetitive behaviors and impaired performance in the preference for social novelty, but not in sociability and cognitive impairments assessed using the object location memory, novel object recognition, and Morris water maze tests. HFD feeding also results in increased numbers of reactive microglia and astrocytes, and exacerbates reductions in dendritic complexity and spine density of hippocampal CA1 pyramidal neurons. Furthermore, we demonstrate that chronic treatment with minocycline, a semisynthetic tetracycline-derived antibiotic, rescues the observed behavioral and morphological deficits in Cc2d1a cKO mice fed with HFD. Collectively, these findings highlight an aggravating role of HFD in pre-existing autistic-like phenotypes and suggest that minocycline treatment can alleviate abnormal neuronal morphology and behavioral symptoms associated with ASD resulted from the interplay between genetic and environmental risk factors. Graphical Abstract: [Figure not available: see fulltext.].

原文English
頁(從 - 到)1331-1352
頁數22
期刊Molecular Neurobiology
60
發行號3
DOIs
出版狀態Published - 2023 3月

All Science Journal Classification (ASJC) codes

  • 神經內科
  • 細胞與分子神經科學
  • 神經科學(雜項)

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