Oral Session

Oral Session 18 一般口演18

O18-1 D1-type Receptors in Prefrontal Cortex Associate with Cognitive Impulsivity: Impact of Methamphetamine Use 前頭前皮質のドパミンD1受容体結合能と衝動性の関連 Okita Kyoji（沖田恭治）¹，Mandelkern Mark²，Dean Andy²，London Edythe² ¹Dept. of Clinical Neuroimaging, Integrative Brain Imaging Center, National Center of Neurology and Psychiatry ²University of California, Los Angeles, Los Angeles, US Individuals with stimulant-drug dependence have repeatedly been shown to have greater impulsivity, and is considered to be a factor contributing to vulnerabilities to drug dependence. Ample evidence suggests the involvement of dopamine, a neurotransmitter which exerts effects not only on motor function but also neurocognitive functions, in impulsivity. Prefrontal cortex is assumed to play a substantial role in impulsive control through its ‘top-down’ modulation. It has been shown D1-type receptor availability measured as binding potential (BPND) in dorsolateral prefrontal cortex (DLPFC) in schizophrenia-spectrum disorders is higher than controls and associated with working memory performance. Working memory supposedly helps impulsive control, also a recent meta-analysis demonstrates that DLPFC function commonly underlie working memory and impulsivity. Nevertheless, little has been reported on D1-type receptor in individuals with methamphetamine (MA) dependence and its potential relationship with impulsivity. In this study, positron emission tomography (PET) was utilized to measure D1-type BPND in DLPFC in 18 healthy-control subjects and 19 with MA dependence. D1-type BPND in DLPFC was higher in MA group than control group. In controls, but not in MA group, the BPND was associated with impulsivity measured with Barratt Impulsiveness Scale and working memory measured with Trail Making Task and Spatial Sternberg Task. These results suggest an important role of DLPFC D1-type receptors in impulsivity and other mechanism(s) contributing greater impulsivity in MA dependence. All procedures were approved by the Institution Review Boards of UCLA and VA Greater Los Angeles.		O18-2 SAM68-specific splicing controls proper 3'UTR isoform selection of interleukin 1-receptor accessory protein through ALE usage SAM68はシナプス形成因子IL1RAcPの3'UTRアイソファーム選択を制御する Iijima Takatoshi（飯島崇利）¹，飯島陽子¹，田中正視¹，鈴木暁子¹，Scheiffele Peter² ¹Tokai University Institute of Innovative Science and Technology, Medical Division ²Biozentrum, University of Basel, Basel, Switzerland Neuronal alternative splicing is dynamically regulated in a spatiotemporal fashion. We previously found that STAR family proteins (SAM68, SLM1, SLM2) regulate spatiotemporal alternative splicing in the nervous system. However, the whole aspect of alternative splicing programs governed by STARs remains unclear. We deciphered the alternative splicing programs of SAM68 and SLM1 proteins using transcriptomics. Here, we reveal that SAM68 and SLM1 encode distinct alternative splicing programs; SAM68 preferentially controls alternative last exon (ALE) splicing. Interleukin 1-receptor accessory protein (Il1rap) is a novel target for SAM68. The usage of Il1rap ALEs results in mainly two variants encoding two functionally different isoforms, a membrane-bound (mIL1RAcP) and a soluble (sIL1RAcP) type. The brain exclusively expresses mIL1RAcP. SAM68 knockout results in remarkable conversion into sIL1RAcP in the brain, which significantly disturbs IL1RAcP neuronal function. Thus, we uncovered the critical role of proper neuronal isoform selection through ALE choice by the SAM68-specific splicing program.

O18-3 The influence of handedness and BDNF Val157Met on Cerebral Responses to Language Processing and Human Voice Perception 聴覚言語処理・音声認識関連賦活に対する利き手とBDNF Val157Metの影響に関するfMRI研究 Koeda Michihiko（肥田道彦） Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan Background and purpose: Concerning brain activity in language processing, we reported that language dominance is left-hemispheric if the score of Edinburgh handedness inventory (EHI) is greater than 50. However, it is unclear whether influences of handedness, its family history, and other biological factors of brain function exist or not. We aimed to investigate how handedness, family history of non-right-hander, and phenotype of BDNFVal157Met influence auditory brain function. Methods: 108 healthy subjects participated in the present study. They were scanned by functional MRI while listening to voice or non-voice, and sentences. Brain activity was analyzed by statistical parametric mapping (SPM). Further, BDNFVal157Met was examined, and the influence of this SNP was also evaluated. Results: As for brain activation in auditory processing, significantly less activation was observed in the anterior part of the left superior temporal gyrus (STG) in subjects with a family history of non-right-handers compared with those without such family history. The results of analysis of variance for 3 factors (handedness, BDNFValMet, brain activation in language processing) showed 1) significant main effect of handedness, and 2) interaction effect between handedness and BDNFVal157Met in the posterior part of STG. Further, this (handedness-BDNFVal157Met) interaction effect was also observed in the same region, as well as voice-specific response. Summary: These findings indicate that 1) brain activity of the anterior part of STG in auditory processing is influenced by handedness or family history, 2) interaction effect between handedness and BDNFVal157Met exists in the cerebral response to auditory language processing as well as voice-specific response.