Article
Chemistry, Medicinal
Kouji Fukuyama, Motohiro Okada
Summary: The study revealed that the effects of zotepine on astroglial L-glutamate release are concentration-dependent and time-dependent, likely through Akt signaling pathway activation leading to enhanced function of astroglial hemichannels, ultimately resulting in increased L-glutamate release. These findings suggest that enhanced astroglial L-glutamatergic transmission induced by zotepine is partially involved in its mood-stabilising and proconvulsive actions.
Article
Biochemistry & Molecular Biology
Motohiro Okada, Kouji Fukuyama, Eishi Motomura
Summary: Recent pharmacological studies have shown that the modulation of tripartite-synaptic transmission plays important roles in the pathophysiology of schizophrenia, mood disorders, and adverse reactions. This study investigated the effects of quetiapine on astrocytes and the rat hypothalamus, and found that quetiapine has complex pharmacological features, including activation of signaling pathways and downregulation of certain proteins. The results suggest that the 5-HT7R inverse agonistic action of quetiapine may play a role in preventing adverse reactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jin Kono, Masakatsu Ueda, Atsushi Sengiku, Sylvia O. Suadicani, Osamu Ogawa, Hiromitsu Negoro
Summary: The study suggests that urothelial Cx43 mediated ATP signaling and coordination of urothelial activity are essential for proper perception and regulation of responses to bladder distension in the animals' awake, active phase. This research highlights the significant role of Cx43 in bladder function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Meng Chen, Guobin Li, Lan Zhang, Kaiting Ning, Baoqiang Yang, Jean X. Jiang, Dong-En Wang, Huiyun Xu
Summary: Osteocytes can release small molecules through Cx43 channels, affecting metabolic pathways related to inflammation and oxidative stress. This study identified potential metabolites released by osteocytes through Cx43 channels, providing new insights into the regulatory mechanisms of osteocytes on themselves and other cells.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Axelle Cooreman, Anne Caufriez, Andres Tabernilla, Raf Van Campenhout, Kaat Leroy, Prashant Kadam, Julen Sanz Serrano, Bruna dos Santos Rodrigues, Pieter Annaert, Mathieu Vinken
Summary: This study investigated the effects of several drugs proposed for treating COVID-19 on Cx43 hemichannels. The results showed that a combination of lopinavir and ritonavir, as well as remdesivir, reduced Cx43 mRNA levels, but none of the drugs affected Cx43 protein expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Kouji Fukuyama, Eishi Motomura, Motohiro Okada
Summary: This study investigates the effects of Brexpiprazole on protein expression, intracellular signaling, and cAMP levels in astrocytes and rat hypothalamus. The results suggest that Brexpiprazole has complex pharmacological features, with partial agonistic action on 5-HT1AR and inverse agonist-like action on 5-HT7R. The suppressive effects of Brexpiprazole on 5-HT7R play an important role in its antidepressive and mood-stabilizing actions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Psychiatry
Laura Orsolini, Silvia Bellagamba, Virginio Salvi, Umberto Volpe
Summary: This article describes a 20-year-old patient with clozapine-resistant schizophrenia and comorbid cannabinoid use disorder, who was successfully treated with a combination of clozapine and brexpiprazole, and later switched to clozapine with long-acting injectable aripiprazole.
ASIAN JOURNAL OF PSYCHIATRY
(2022)
Article
Medicine, Research & Experimental
Motohiro Okada, Kouji Fukuyama, Takashi Shiroyama, Yuto Ueda
Summary: The study investigated the effects of brivaracetam on astroglial L-glutamate release and the interaction with SV2A and Cx43 expression. The results suggest that suppression of TNF-α-induced neuronal excitability by inhibiting ectopic SV2A contributes to the antiepileptic/anticonvulsive mechanism of brivaracetam action.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Olivia E. Crouthamel, Leping Li, Michael T. Dilluvio, Thomas W. White
Summary: Mutations in the GJA1 gene encoding connexin43 (Cx43) have been linked to various rare genetic disorders, including those affecting the skin. This study investigated the functional consequences of a specific Cx43 mutation (Cx43-G38E) associated with a novel human phenotype. The research showed that the mutation increased the activity of hemichannels, suggesting a potential role in skin and skeletal disorders caused by Cx43 mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Yi Zhu
Summary: Connexin43 is a crucial protein in the family that not only plays a critical role in gap junctions but also has various functions independent of gap junctions. It forms different-sized polypeptides through distinct mechanisms and functions in different cellular compartments. Research on Connexin43 will enhance our understanding of how genes increase their functions and may guide the development of therapies for metabolic conditions, cancer, and other diseases.
Article
Neurosciences
Guo-Li Zhao, Hong Zhou, Yun-Hui Guo, Shu-Min Zhong, Han Zhou, Fang Li, Bo Lei, Zhongfeng Wang, Yanying Miao
Summary: In this study, the expression of connexin 43 (Cx43) was found to be regulated in glial cells in a glaucoma mouse model, indicating its involvement in the pathogenesis of glaucoma. The Rac1/PAK1/Cx43/ATP pathway was identified as a potential mechanism underlying the interaction between astrocytes and retinal ganglion cells (RGCs), providing insight into potential therapeutic strategies for glaucoma management.
Article
Medicine, Research & Experimental
Kouji Fukuyama, Eishi Motomura, Takashi Shiroyama, Motohiro Okada
Summary: This study investigated the effects of lurasidone on astroglial L-glutamate release, connexin43, ERK, AKT, and 5-HT receptors, and found that its antidepressive mood-stabilising effects are different from other drugs.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Geriatrics & Gerontology
Senbo An, Shengyuan Zheng, Zijun Cai, Siyu Chen, Chen Wang, Yusheng Li, Zhenhan Deng
Summary: This article summarizes the function of Connexin43 in musculoskeletal tissues and its abnormal expression in related disorders. Studies have shown that Connexin43 plays an important role in bone homeostasis regulation. By forming gap junctions and hemichannels, Connexin43 can participate in cellular regulation and signaling. This article highlights the importance of Connexin43 as a potential target for the treatment of related bone and muscle disorders and emphasizes the need for further research.
Article
Biochemistry & Molecular Biology
Kouji Fukuyama, Motohiro Okada
Summary: In this study, the effects of brivaracetam and levetiracetam on astroglial cell response to different types of high-frequency oscillations were investigated. It was found that brivaracetam and levetiracetam inhibited the activation of astroglial cells induced by fast-ripple high-frequency oscillation, while levetiracetam exhibited inhibitory effects on astroglial cell response to physiological ripple high-frequency oscillation. These findings are important for understanding the mechanisms of action of these drugs and their adverse behavioral/psychiatric effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Takashi Shiroyama, Kouji Fukuyama, Motohiro Okada
Summary: The study investigated the effects of antidepressants on astrocyte transmission, showing that 5-HT1A receptor and 5-HT7 receptor play different roles in this process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Motohiro Okada
Summary: ADSHE, caused by CHNRA4 mutation, is a genetic epilepsy where mutant molecules play important roles in epileptogenesis/ictogenesis. Research involving experimental models has revealed the pathomechanisms of ADSHE, proposing a hypothesis associated with tripartite synaptic transmission induced by mutant ACh receptors.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Clinical Neurology
Kazunori Nomura, Munehito Yoshida, Motohiro Okada, Yosuke Nakamura, Kenichi Yawatari, Enshi Nakayama
Summary: This retrospective cohort study investigated the effectiveness and safety of a gelatin-thrombin matrix sealant (GTMS) during microendoscopic laminectomy (MEL) for lumbar spinal canal stenosis (LSCS). The use of GTMS was associated with a reduction in postoperative drainage volume and did not significantly affect the revision rate for spinal epidural hematoma (PSEH). Regardless of GTMS use, the clinical outcomes improved significantly after the surgery.
GLOBAL SPINE JOURNAL
(2023)
Article
Clinical Neurology
Eishi Motomura, Hisashi Tanii, Yasuhiro Kawano, Koji Inui, Motohiro Okada
Summary: This study investigates the association between the prepulse inhibition (PPI) index and the COMT gene polymorphism and explores the role of dopamine metabolism in the prefrontal cortex. The results show that the PPI level in Met-carriers is significantly higher than that in Val/Val individuals, suggesting that dopamine may play a role in PPI and this index has the potential to be used for identifying intermediate phenotypes in psychiatric disorders.
PSYCHIATRY RESEARCH-NEUROIMAGING
(2022)
Article
Environmental Sciences
Yasuhiro Kawano, Ryusuke Matsumoto, Eishi Motomura, Takashi Shiroyama, Motohiro Okada
Summary: This study used vector autoregression models to analyze the temporal bidirectional causalities between the numbers of newly confirmed COVID-19 cases and individual mobilisations with consumption motives in different prefecture borders in Japan. The study found that mobilisation with consumption in pubs contributed to the spread of COVID-19 in different regions, and the pattern was influenced by regional characteristics. Additionally, the study found that government measures to suppress pub visitors were partially effective, but the causal mobilisations with consumption motives were not identical nationwide and regional characteristics should be considered.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Article
Public, Environmental & Occupational Health
Ryusuke Matsumoto, Yasuhiro Kawano, Eishi Motomura, Takashi Shiroyama, Motohiro Okada
Summary: During the early stages of the COVID-19 pandemic, most countries/regions did not see an increase in suicides. However, Japan was an exception, with an increase in female suicides while male suicides remained unchanged. Personal consumption and standardized suicide death rates were analyzed to understand the trends in suicides during the pandemic. It was found that during the first wave of the pandemic, suicide rates for both sexes slightly decreased but increased during the second half of 2020. The suicide rates for females under 70 years old and males under 40 years old continued to increase in 2021. Changes in personal consumption, such as decreased expenditures on out-of-home recreations and increased expenditures on home-based recreations, were observed. Increased expenditures on internet/mobile communication were associated with an increase in suicide rates for both sexes, while increased expenditures on content distributions were associated with an increase in suicide rates for females only. Decreased expenditures on pubs were related to an increase in suicide rates for both sexes in non-metropolitan areas. These findings suggest that the changes in individual lifestyles during the pandemic, including more time spent at home and decreased social interactions, contribute to an increased risk of suicide.
FRONTIERS IN PUBLIC HEALTH
(2022)
Review
Biochemistry & Molecular Biology
Kouji Fukuyama, Eishi Motomura, Motohiro Okada
Summary: Although the contributions of 5-HT7 function to clinical efficacy and pathophysiology are not fully understood, lurasidone and vortioxetine have higher binding affinity to 5-HT7 compared to other antipsychotics and antidepressants. While the expected rapid onset of antidepressant effects due to 5-HT7 inhibition has not been observed with these drugs, clinical studies suggest that 5-HT7 inhibition improves the quality of life for patients with schizophrenia and mood disorders by enhancing cognition. Furthermore, 5-HT7 inhibition may mitigate antipsychotic-induced weight gain and metabolic complications. Preclinical studies for the development of 5-HT7 modulation against neurodevelopmental disorders and neurodegenerative diseases are ongoing. Various findings indicate the possibility of using 5-HT7 modifications for improving neuronal transmission and addressing microstructure abnormalities in neurotransmission networks.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Psychiatry
Motohiro Okada
Summary: Similar to other countries, the Japanese government took quick preventive measures against the increasing suicide rates during the pandemic, but was unable to suppress the rise. Suicide mortality rates among individuals under 20 and females aged 20-39 significantly increased during the pandemic, despite showing a decreasing trend before its onset. Additionally, higher unemployment rates were associated with increased suicide mortality for both sexes before the pandemic, but this relationship was not observed during the pandemic for females.
ASIAN JOURNAL OF PSYCHIATRY
(2022)
Letter
Psychiatry
Yuki Ito, Masahiko Murata, Omori Taku, Kouji Fukuyama, Eishi Motomura, Kaoru Dohi, Motohiro Okada
ASIAN JOURNAL OF PSYCHIATRY
(2023)
Correction
Health Care Sciences & Services
Toshiki Hasegawa, Kouhei Nishikawa, Yuko Tamura, Tomoka Oka, Aiko Urawa, Saori Watanabe, Shugo Mizuno, Motohiro Okada
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Nutrition & Dietetics
Kouji Fukuyama, Eishi Motomura, Motohiro Okada
Summary: Lurasidone and quetiapine are effective atypical mood-stabilizing antipsychotics, but have different effects on weight gain and metabolic complications. The underlying reasons for these differences are still unknown.
Letter
Psychiatry
Ryusuke Matsumoto, Eishi Motomura, Motohiro Okada
ASIAN JOURNAL OF PSYCHIATRY
(2023)
Article
Medicine, General & Internal
Motohiro Okada, Ryusuke Matsumoto, Takashi Shiroyama, Eishi Motomura
Summary: The suicide mortality rate per 100 000 population (SMRP) in Japan has shown a consistent decrease until the COVID-19 pandemic outbreak. This study aimed to identify trends and factors associated with suicidal mortality and motives among students in Japan from 2007 to 2022. The findings revealed that school-related, health-related, and family-related problems were major motives for suicide among students. The impact of health-related and family-related motives varied with age, and the rates associated with interpersonal relationships increased significantly during the pandemic.
Article
Health Care Sciences & Services
Ryusuke Matsumoto, Eishi Motomura, Motohiro Okada
Summary: In Japan, suicides had been decreasing before the COVID-19 pandemic, but increased after the outbreak. Analysis of data from 2009 to 2022 showed that fluctuations in suicide rates had three patterns, including a positive discontinuity synchronized with the pandemic, attenuations of decreasing trends before the pandemic, and turning points from decreasing to increasing or unchanged after the pandemic. Unemployment rate was found to have a relationship with suicide rates, and the duration and reasons for unemployment also affected the changes in suicide rates.
Article
Health Care Sciences & Services
Motohiro Okada, Ryusuke Matsumoto, Eishi Motomura, Takashi Shiroyama, Masahiko Murata
Summary: This study analyzes the trend change in suicide rates during the COVID-19 pandemic in Japan and finds an increase in rates in 2020 and 2021. The trend change is associated with gender, region, suicide method, and household. The study also finds that suicide rates among those who hang themselves at home and single-person households fluctuate in synchronization with the overall rates. Furthermore, the increase in the number of infected patients and diagnostic examinations is positively and negatively related to the suicide rate, respectively.
LANCET REGIONAL HEALTH-WESTERN PACIFIC
(2022)
