Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models

© 2020, The Author(s). Autism spectrum disorder (ASD) is a continuum of neurodevelopmental disorders and needs new therapeutic approaches. Recently, oxytocin (OXT) showed potential as the first anti-ASD drug. Many reports have described the efficacy of intranasal OXT therapy to improve the core symptoms of patients with ASD; however, the underlying neurobiological mechanism remains unknown. The OXT/oxytocin receptor (OXTR) system, through the lateral septum (LS), contributes to social behavior, which is disrupted in ASD. Therefore, we selectively express hM3Dq in OXTR-expressing (OXTR+) neurons in the LS to investigate this effect in ASD mouse models developed by environmental and genetic cues. In mice that received valproic acid (environmental cue), we demonstrated successful recovery of impaired social memory with three-chamber test after OXTR+ neuron activation in the LS. Application of a similar strategy to Nl3R451C knock-in mice (genetic cue) also caused successful recovery of impaired social memory in single field test. OXTR+ neurons in the LS, which are activated by social stimuli, are projected to the CA1 region of the hippocampus. This study identified a candidate mechanism for improving core symptoms of ASD by artificial activation of DREADDs, as a simulation of OXT administration to activate OXTR+ neurons in the LS

オレフィン オヨビ ケトン ノ ショクバイテキ フセイ ヒドロシリルカ ハンノウ ニ カンスル ケンキュウ

京都大学0048新制・課程博士工学博士甲第1635号工博第424号新制||工||312(附属図書館)UT51-50-G178京都大学大学院工学研究科合成化学専攻(主査)教授 熊田 誠, 教授 三枝 武夫, 教授 古川 淳二学位規則第5条第1項該当Kyoto UniversityDFA

The concise synthesis of chiral tfb ligands and their application to the rhodium-catalyzed asymmetric arylation of aldehydes

New C2-symmetric tetrafluorobenzobarrelene ligands were prepared and applied successfully to the rhodium-catalyzed asymmetric addition of arylboronic acids to aromatic aldehydes giving chiral diarylmethanols in high yield with high enantioselectivity

Rhodium-catalyzed arylzincation of alkynes : ligand control of 1,4-migration selectivity

The addition of arylzinc reagents ArZnCl 1 to alkynes 2 was found to be catalyzed by rhodium complexes in the presence of a catalytic amount of zinc chloride. The selectivity in giving 2-arylalkenylzinc species 3 or ortho-alkenylarylzinc species 4, the latter of which is generated through 1,4-Rh migration from alkenyl to aryl in the catalytic cycle, is controlled by the ligands on rhodium. Ligands cod and binap gave 3 and 4, respectively, with high selectivity.MOE (Min. of Education, S’pore