Matches in SemOpenAlex for { <https://semopenalex.org/work/W2897468495> ?p ?o ?g. }
- W2897468495 abstract "Autism spectrum disorder (ASD) is a common neurobehavioral disorder with limited treatment options. Activation of p38 MAPK signaling networks has been identified in ASD, and p38 MAPK signaling elevates serotonin (5-HT) transporter (SERT) activity, effects mimicked by multiple, hyperfunctional SERT coding variants identified in ASD subjects. Mice expressing the most common of these variants (SERT Ala56) exhibit hyperserotonemia, a biomarker observed in ASD subjects, as well as p38 MAPK-dependent SERT hyperphosphorylation, elevated hippocampal 5-HT clearance, hypersensitivity of CNS 5-HT1A and 5-HT2A/2C receptors, and behavioral and gastrointestinal perturbations reminiscent of ASD. As the α-isoform of p38 MAPK drives SERT activation, we tested the hypothesis that CNS-penetrant, α-isoform-specific p38 MAPK inhibitors might normalize SERT Ala56 phenotypes. Strikingly, 1-week treatment of adult SERT Ala56 mice with MW150, a selective p38α MAPK inhibitor, normalized hippocampal 5-HT clearance, CNS 5-HT1A and 5-HT2A/2C receptor sensitivities, social interactions, and colonic motility. Conditional elimination of p38α MAPK in 5-HT neurons of SERT Ala56 mice restored 5-HT1A and 5-HT2A/2C receptor sensitivities as well as social interactions, mirroring effects of MW150. Our findings support ongoing p38α MAPK activity as an important determinant of the physiological and behavioral perturbations of SERT Ala56 mice and, more broadly, supports consideration of p38α MAPK inhibition as a potential treatment for core and comorbid phenotypes present in ASD subjects." @default.
- W2897468495 created "2018-10-26" @default.
- W2897468495 creator A5010714387 @default.
- W2897468495 creator A5019329770 @default.
- W2897468495 creator A5022425643 @default.
- W2897468495 creator A5029246358 @default.
- W2897468495 creator A5040278204 @default.
- W2897468495 creator A5053558359 @default.
- W2897468495 creator A5054573678 @default.
- W2897468495 creator A5082550457 @default.
- W2897468495 date "2018-10-08" @default.
- W2897468495 modified "2023-10-18" @default.
- W2897468495 title "p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse" @default.
- W2897468495 cites W1541506878 @default.
- W2897468495 cites W1597626394 @default.
- W2897468495 cites W1884507993 @default.
- W2897468495 cites W1897852281 @default.
- W2897468495 cites W1906903025 @default.
- W2897468495 cites W1907864108 @default.
- W2897468495 cites W1917634040 @default.
- W2897468495 cites W1921335093 @default.
- W2897468495 cites W1935154815 @default.
- W2897468495 cites W1963736913 @default.
- W2897468495 cites W1964358779 @default.
- W2897468495 cites W1966784044 @default.
- W2897468495 cites W1968298980 @default.
- W2897468495 cites W1970124769 @default.
- W2897468495 cites W1973491179 @default.
- W2897468495 cites W1974433428 @default.
- W2897468495 cites W1976101979 @default.
- W2897468495 cites W1978231228 @default.
- W2897468495 cites W1986624226 @default.
- W2897468495 cites W1989784279 @default.
- W2897468495 cites W1993405392 @default.
- W2897468495 cites W1995824400 @default.
- W2897468495 cites W1996120254 @default.
- W2897468495 cites W2002149445 @default.
- W2897468495 cites W2004995928 @default.
- W2897468495 cites W2007077740 @default.
- W2897468495 cites W2008737741 @default.
- W2897468495 cites W2015870346 @default.
- W2897468495 cites W2017519608 @default.
- W2897468495 cites W2024192983 @default.
- W2897468495 cites W2029663297 @default.
- W2897468495 cites W2035017299 @default.
- W2897468495 cites W2036553842 @default.
- W2897468495 cites W2036606290 @default.
- W2897468495 cites W2039144704 @default.
- W2897468495 cites W2044315491 @default.
- W2897468495 cites W2046438298 @default.
- W2897468495 cites W2046989317 @default.
- W2897468495 cites W2048377822 @default.
- W2897468495 cites W2052784390 @default.
- W2897468495 cites W2053896453 @default.
- W2897468495 cites W2054586661 @default.
- W2897468495 cites W2060203263 @default.
- W2897468495 cites W2065313926 @default.
- W2897468495 cites W2065380220 @default.
- W2897468495 cites W2071201894 @default.
- W2897468495 cites W2071797996 @default.
- W2897468495 cites W2074981365 @default.
- W2897468495 cites W2075918530 @default.
- W2897468495 cites W2079773266 @default.
- W2897468495 cites W2080747161 @default.
- W2897468495 cites W2082152632 @default.
- W2897468495 cites W2082179080 @default.
- W2897468495 cites W2083040623 @default.
- W2897468495 cites W2084971731 @default.
- W2897468495 cites W2085708523 @default.
- W2897468495 cites W2086063461 @default.
- W2897468495 cites W2086075088 @default.
- W2897468495 cites W2087803534 @default.
- W2897468495 cites W2091882220 @default.
- W2897468495 cites W2093666272 @default.
- W2897468495 cites W2095596791 @default.
- W2897468495 cites W2097566770 @default.
- W2897468495 cites W2097785193 @default.
- W2897468495 cites W2099789197 @default.
- W2897468495 cites W2100695475 @default.
- W2897468495 cites W2104220482 @default.
- W2897468495 cites W2108417757 @default.
- W2897468495 cites W2109066409 @default.
- W2897468495 cites W2110143479 @default.
- W2897468495 cites W2110505280 @default.
- W2897468495 cites W2116134868 @default.
- W2897468495 cites W2116921598 @default.
- W2897468495 cites W2118507010 @default.
- W2897468495 cites W2118741643 @default.
- W2897468495 cites W2119262860 @default.
- W2897468495 cites W2119744351 @default.
- W2897468495 cites W2124023336 @default.
- W2897468495 cites W2124241220 @default.
- W2897468495 cites W2126866445 @default.
- W2897468495 cites W2132438753 @default.
- W2897468495 cites W2136328934 @default.
- W2897468495 cites W2141910384 @default.
- W2897468495 cites W2144628640 @default.
- W2897468495 cites W2149174165 @default.
- W2897468495 cites W2153657359 @default.
- W2897468495 cites W2155948158 @default.