Matches in SemOpenAlex for { <https://semopenalex.org/work/W4362665340> ?p ?o ?g. }
- W4362665340 abstract "Abstract Background Microdeletion of the 16p11.2 region of the human chromosome is a prevalent genetic factor for autism spectrum disorder (ASD) and other neurodevelopmental disorders, but its pathogenic mechanism remains unclear, and effective treatments for 16p11.2 microdeletion syndrome are lacking. Emerging evidence suggests that the gut microbiota and its metabolites are inextricably linked to host behavior through the gut-brain axis, and are therefore implicated in ASD development. However, the functional roles of microbial metabolites in the context of 16p11.2 microdeletion are yet to be elucidated. This study aims to investigate the therapeutic potential of indole-3-propionic acid (IPA), a gut microbiota metabolite, in addressing behavioral and pathological deficits associated with 16p11.2 microdeletion, as well as the underlying molecular mechanisms. Results Mice with the 16p11.2 microdeletion (16p11.2 +/− ) showed dysbiosis of the gut microbiota and a significant decrease in IPA levels in feces and blood circulation. Further, these mice exhibited significant social and cognitive impairments, and abnormal activation of hippocampal dentate gyrus neurons, which was accompanied by an imbalance of inhibitory synaptic transmission in this region. However, oral supplementation of IPA significantly mitigated these alterations, thereby ameliorating the social and cognitive deficits of the mice. Remarkably, IPA administration significantly increased the phosphorylation level of ERK1, a protein encoded by the Mapk3 gene in the 16p11.2 region, without affecting the transcription and translation of the Mapk3 gene. Conclusions Our study reveal that 16p11.2 +/− leads to a decline in gut metabolite IPA levels, and that supplementation with IPA can reverse the associated histological and electrophysiological changes and behavioral defects in 16p11.2 +/− mice. These findings provide new insights into the critical role of gut microbial metabolites in ASD pathogenesis and presents a promising treatment treatment strategy for social and cognitive deficit disorders, such as 16p11.2 microdeletion syndrome." @default.
- W4362665340 created "2023-04-07" @default.
- W4362665340 creator A5003684397 @default.
- W4362665340 creator A5006915668 @default.
- W4362665340 creator A5010141139 @default.
- W4362665340 creator A5020208349 @default.
- W4362665340 creator A5029323089 @default.
- W4362665340 creator A5035288269 @default.
- W4362665340 creator A5036427905 @default.
- W4362665340 creator A5058716440 @default.
- W4362665340 creator A5060155994 @default.
- W4362665340 creator A5064383898 @default.
- W4362665340 creator A5069255958 @default.
- W4362665340 creator A5074825546 @default.
- W4362665340 date "2023-04-06" @default.
- W4362665340 modified "2023-09-26" @default.
- W4362665340 title "The gut metabolite indole-3-propionic acid activates ERK1 to restore social function and hippocampal inhibitory synaptic transmission in a 16p11.2 microdeletion mouse model" @default.
- W4362665340 cites W1516995431 @default.
- W4362665340 cites W1743462958 @default.
- W4362665340 cites W1808144476 @default.
- W4362665340 cites W1969615942 @default.
- W4362665340 cites W1971321176 @default.
- W4362665340 cites W1973419361 @default.
- W4362665340 cites W1978262894 @default.
- W4362665340 cites W1987839624 @default.
- W4362665340 cites W2001250682 @default.
- W4362665340 cites W2004784996 @default.
- W4362665340 cites W2023621960 @default.
- W4362665340 cites W2027187941 @default.
- W4362665340 cites W2032319596 @default.
- W4362665340 cites W2035001975 @default.
- W4362665340 cites W2052578932 @default.
- W4362665340 cites W2054676430 @default.
- W4362665340 cites W2055380229 @default.
- W4362665340 cites W2063370018 @default.
- W4362665340 cites W2072034250 @default.
- W4362665340 cites W2075361934 @default.
- W4362665340 cites W2078328563 @default.
- W4362665340 cites W2088985836 @default.
- W4362665340 cites W2091199294 @default.
- W4362665340 cites W2092912827 @default.
- W4362665340 cites W2098277878 @default.
- W4362665340 cites W2102492718 @default.
- W4362665340 cites W2121622229 @default.
- W4362665340 cites W2178837340 @default.
- W4362665340 cites W2210849364 @default.
- W4362665340 cites W2264590724 @default.
- W4362665340 cites W2599051363 @default.
- W4362665340 cites W2620781914 @default.
- W4362665340 cites W2733572936 @default.
- W4362665340 cites W2763013404 @default.
- W4362665340 cites W2769517706 @default.
- W4362665340 cites W2769544142 @default.
- W4362665340 cites W2789447616 @default.
- W4362665340 cites W2790370793 @default.
- W4362665340 cites W2797411641 @default.
- W4362665340 cites W2801166051 @default.
- W4362665340 cites W2803873435 @default.
- W4362665340 cites W2806466487 @default.
- W4362665340 cites W2807728333 @default.
- W4362665340 cites W2808912478 @default.
- W4362665340 cites W2886401819 @default.
- W4362665340 cites W2886989735 @default.
- W4362665340 cites W2902398393 @default.
- W4362665340 cites W2907898681 @default.
- W4362665340 cites W2943548508 @default.
- W4362665340 cites W2948003108 @default.
- W4362665340 cites W2950040155 @default.
- W4362665340 cites W2954924854 @default.
- W4362665340 cites W2965153152 @default.
- W4362665340 cites W2967405540 @default.
- W4362665340 cites W3008031857 @default.
- W4362665340 cites W3014052079 @default.
- W4362665340 cites W3026587634 @default.
- W4362665340 cites W3047642950 @default.
- W4362665340 cites W3068244390 @default.
- W4362665340 cites W3089221670 @default.
- W4362665340 cites W3134480340 @default.
- W4362665340 cites W3188556444 @default.
- W4362665340 cites W3198551709 @default.
- W4362665340 cites W3199355847 @default.
- W4362665340 cites W3201105235 @default.
- W4362665340 cites W3205155997 @default.
- W4362665340 cites W3211562608 @default.
- W4362665340 cites W3212160497 @default.
- W4362665340 cites W4206911826 @default.
- W4362665340 cites W4206941751 @default.
- W4362665340 cites W4212796503 @default.
- W4362665340 cites W4213093937 @default.
- W4362665340 cites W4213099424 @default.
- W4362665340 cites W4213358089 @default.
- W4362665340 cites W4214892880 @default.
- W4362665340 cites W4221094184 @default.
- W4362665340 cites W4283367198 @default.
- W4362665340 cites W4292707894 @default.
- W4362665340 cites W4302004049 @default.
- W4362665340 cites W4313635088 @default.
- W4362665340 cites W4317402061 @default.
- W4362665340 doi "https://doi.org/10.21203/rs.3.rs-2774761/v1" @default.
- W4362665340 hasPublicationYear "2023" @default.