精神疾患におけるマイクログリア由来ニューレグリン発現

Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD. Intriguingly, microglial NRG expression significantly increased in BTBR and socially-isolated mice, while maternal immune activation (MIA) mice exhibited identical NRG expression to controls. Furthermore, we observed a positive correlation between NRG expression in microglia and peripheral blood mononuclear cells (PBMCs) in mice, suggesting that NRG expression in human PBMCs may mirror microglia-derived NRG expression in the human brain. To translate these findings for application in clinical psychiatry, we measured levels of NRG1 splice-variant expression in clinically available PBMCs of patients with ASD. Levels of NRG1 type III expression in PBMCs were positively correlated with impairments in social interaction in children with ASD (as assessed using the Autistic Diagnostic Interview-Revised test: ADI-R). These findings suggest that immune cell-derived NRGs may be implicated in the pathobiology of psychiatric disorders such as ASD.博士（医学）・乙第1404号・平成29年6月28日Copyright © 2017 Elsevier Inc. All rights reserved

Preliminary study on the effects of movement velocity training of the upper limbs on gait ability in older adults: a nonrandomized controlled trial

Saki Yamamoto,1 Akira Iwata,1 Yuki Yano,1 Toshimitsu Ohmine,1 Keisuke Honma,1 Kazuma Senzaki,1 Minami Fujiwara,1 Takayuki Murakami,1 Junji Inoue,1 Yuki Sano,2 Shuji Okagawa,3 Yuta Otsuki,4 Hideyuki Wanaka,5 Masataka Kataoka,1 Hiroshi Iwata61Department of Physical Therapy, Faculty of Comprehensive Rehabilitation, Osaka Prefecture University, Habikino, Osaka, Japan; 2Department of Rehabilitation, Osaka General Medical Center, Osaka, Osaka, Japan; 3Department of Rehabilitation, Tatsumi Hospital, Ikeda, Osaka, Japan; 4Department of Rehabilitation, Kisei Hospital, Osaka, Osaka, Japan; 5Department of Rehabilitation, Kobe Rosai Hospital, Kobe, Hyogo, Japan; 6Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, JapanPurpose: Movement velocity of the limbs or trunk plays an important determinant of gait speed in older adults. Movement velocity-focused training of the lower limbs or trunk has recently been shown to be an effective intervention to improve gait ability. Because movement velocities of various body regions are significantly correlated, movement velocity training of the upper limbs may also be effective for improving gait speed. Therefore, the purpose of this study was to investigate whether movement velocity training of the upper limbs in a seated position is effective for improving gait ability.Patients and methods: This study was a nonrandomized controlled trial. The participants were older adults residing in geriatric health service facilities. They were assigned to the movement velocity training of the upper limbs group (n=26) or control group (n=15). The participants in the training group performed exercises (three times per week for 10 weeks) to move the upper limbs as quickly as possible. The outcomes were gait speed, movement velocity, and quadriceps strength. These measurements were performed preintervention and 4, 8, and 10 weeks after intervention.Results: A significant time–group interaction was found for maximum gait speed and movement velocity of the upper limbs. Bonferroni post-hoc test showed significant improvement in gait speed between preintervention and 10 weeks after intervention in the training group. The movement velocity of the upper limbs was significantly improved between preintervention and 4, 8, and 10 weeks after intervention.Conclusion: Movement velocity training of the upper limbs showed significant and clinically relevant improvements in maximum gait speed at 10 weeks after intervention. This training is a potentially useful intervention and can be safely performed.Keywords: older people, movement velocity training, arm, gait speed, seated positio