Icariin alleviates autistic-like behavior, hippocampal inflammation and vGlut1 expression in adult BTBR mice

• Published in: Behavioural brain research Vol. 445; p. 114384
• Main Authors: Jiang, Peiyan, Zhou, Lianyu, Du, Zhulin, Zhao, Linyang, Tang, Yexi, Fei, Xinghang, Wang, Lian, Li, Dabing, Li, Song, Yang, Hui, Fan, Xiaotang, Liao, Huiling
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 08.05.2023
• Subjects: Animals; Autism; Autism Spectrum Disorder - drug therapy; Autism Spectrum Disorder - metabolism; Autistic Disorder - metabolism; BTBR; Cytokines - metabolism; Disease Models, Animal; Hippocampus; Hippocampus - metabolism; Icariin; Inflammation - metabolism; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Microglia; Neuroinflammation; Neuroinflammatory Diseases; Social Behavior; Icariin; Autism; Neuroinflammation; BTBR; Hippocampus; Microglia
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2023.114384

Autism spectrum disorder (ASD) is a complicated, heterogeneous disorder characterized by social interaction deficits and repetitive stereotypical behaviors. Neuroinflammation and synaptic protein dysregulation have been implicated in ASD pathogenesis. Icariin (ICA) has proven to exert neuroprotective function through anti-inflammatory function. Therefore, this study aimed to clarify the effects of ICA treatment on autism-like behavioral deficits in BTBR mice and whether these changes were related to modifications in the hippocampal inflammation and the balance of excitatory/inhibitory synapses. ICA supplementation (80 mg/kg, once daily for ten days, i.g.) ameliorated social deficits, repetitive stereotypical behaviors, and short-term memory deficit without affecting locomotor activity or anxiety-like behaviors of BTBR mice. Furthermore, ICA treatment inhibited neuroinflammation via decreasing microglia number and the soma size in the CA1 region of the hippocampus, as well as the protein levels of proinflammatory cytokines in the hippocampus of BTBR mice. In addition, ICA treatment also rescued excitatory-inhibitory synaptic protein imbalance by inhibiting the increased vGlut1 level without affecting the vGAT level in the BTBR mouse hippocampus. Collectively, the observed results indicate that ICA treatment alleviates ASD-like features, mitigates disturbed balance of excitatory-inhibitory synaptic protein, and inhibits hippocampal inflammation in BTBR mice, and may represent a novel promising drug for ASD treatment. •Icariin treatment ameliorates social deficits and stereotypical behaviors in adult BTBR mice.•Icariin improves cognitive function in adult BTBR mice.•Icariin inhibits hippocampal neuroinflammation in BTBR mice.•Icariin decreases vGlut1 expression in the hippocampus of BTBR mice.