Article
Neurosciences
Kaoru Beppu, Naoko Kubo, Ko Matsui
Summary: Recent studies have shown that Bergmann glial cells in the cerebellum can effectively amplify excitatory information processing by releasing glutamate, demonstrating interaction between neurons and glia. This finding suggests that a portion of the postsynaptic current in neurons may be mediated by glutamate released from Bergmann glial cells.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Developmental Biology
Osamu Nozawa, Muneaki Miyata, Hajime Shiotani, Takeshi Kameyama, Ryouhei Komaki, Tatsuhiro Shimizu, Toshihiko Kuriu, Yutaro Kashiwagi, Yuka Sato, Michinori Koebisu, Atsu Aiba, Shigeo Okabe, Kiyohito Mizutani, Yoshimi Takai
Summary: We demonstrated that co-cultured neurons induced astrocyte ramifications and formation of tripartite synapses in an in vitro system. The induction of astrocyte ramifications was dependent on neuronal activity and likely involved synaptically-released glutamate and activation of astrocytic mGluR5. Moreover, the Necl2/3 trans-interaction recruited glutamate transporters and K+ channels to the perisynaptic astrocyte processes, enhancing synapse formation and astrocyte functional polarization.
Article
Neurosciences
Anna Bodzeta, Nicky Scheefhals, Harold D. MacGillavry
Summary: The various functions of glutamate in the brain are mediated by ionotropic and metabotropic glutamate receptors, which modulate synaptic transmission and plasticity. mGluRs play roles at both presynaptic and postsynaptic sites, acting as essential signal integrators that couple mechanisms of transmission and plasticity.
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
Neurosciences
Yuryanni A. Rodriguez, Jennifer K. Roebber, Gennady Dvoryanchikov, Vivien Makhoul, Stephen D. Roper, Nirupa Chaudhari
Summary: Research showed that Type I cells in mammalian taste buds primarily respond to ATP, not to other chemicals or taste stimuli. The study suggests that Type I cells may sense chemosensory activation and participate in synaptic signaling, similar to glial cells in the CNS.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Giovanna Crivellaro, Angelita Tottene, Marina Vitale, Marcello Melone, Giorgio Casari, Fiorenzo Conti, Mirko Santello, Daniela Pietrobon
Summary: Migraine is a common but poorly understood sensory circuit disorder. Mouse models of familial hemiplegic migraine show increased susceptibility to cortical spreading depression, which is mainly caused by reduced expression of astrocytic Na+, K+-ATPases. The enhanced NMDAR activation in FHM2 mice is activity-dependent and can be rescued by inhibition of GluN1-N2B NMDARs.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Neurosciences
Sweta Adhikary, Elizabeth R. Jaeckel, William T. Birdsong
Summary: Endogenous adenosine is crucial in neural circuits and its accumulation is regulated by mu opioid receptors and cAMP-dependent mechanism. This study also reveals the role of D1R-positive MSNs in regulating synaptic inputs.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Andres M. Baraibar, Lindsey Belisle, Giovanni Marsicano, Carlos Matute, Susana Mato, Alfonso Araque, Paulo Kofuji
Summary: Microcircuits in the neocortex are functionally organized along layers and columns, and astrocytes play a role in the functional organization and bidirectional interaction between neurons. Activation of astrocytes by endocannabinoids leads to an increase in Ca2+ levels, ATP/adenosine release, and temporary synaptic depression between layer 5 pyramidal neurons at relatively distant synapses. This form of heteroneuronal synaptic depression is specific to cortical columns and layers, depending on layer-specific neuron-to-astrocyte signaling.
Review
Biochemistry & Molecular Biology
Hagar Bauminger, Inna Gaisler-Salomon
Summary: This study discusses the role of glutamate homeostasis in schizophrenia-related cognitive dysfunction. They focus on cognitive domains that can be measured in humans and rodents, and discuss the relevance of glutamate alterations in these domains. They find that the interaction between astrocytes and neurons is crucial for cognition, and that presynaptic and postsynaptic components play a critical role in maintaining glutamate homeostasis and cognitive well-being.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Shreya Malhotra, Gokulakrishna Banumurthy, Reagan L. Pennock, Jada H. Vaden, Izumi Sugihara, Linda Overstreet-Wadiche, Jacques Wadiche
Summary: Neurotransmitter spillover, a form of communication not easily predicted by anatomy, is regulated by the patterned expression of the excitatory amino acid transporter 4 in the cerebellum. Through experiments using Aldolase C-Venus knock-in mice, researchers found that heterogeneity in EAAT4 expression is the primary determinant of differential spillover between neuronal microzones. This study highlights how neuronal glutamate transporters limit extrasynaptic transmission in a non-cell-autonomous manner and provides new insights into the functional specialization of cerebellar microzones.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Devin K. Binder, Christian Steinhaeuser
Summary: Changes in astrocyte channels, transporters, and metabolism are closely linked to seizure generation and epilepsy, with alterations in potassium, glutamate, water and adenosine homeostasis contributing to hyperexcitability and epileptogenesis. Understanding the role of astrocytes in epilepsy offers potential for identifying novel astrocyte-specific therapeutic targets.
NEUROCHEMICAL RESEARCH
(2021)
Article
Neurosciences
Leonid P. Savtchenko, Kaiyu Zheng, Dmitri A. Rusakov
Summary: Research has shown that high-affinity glutamate transporters can efficiently constrain extrasynaptic spread of glutamate, even when diffusion passages are relatively open, highlighting the importance of perisynaptic environment in preventing glutamate escape.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Eichi Narimatsu, Ryuichiro Kakizaki, Kazuhito Nomura, Keigo Sawamoto, Kazunobu Takahashi, Shuji Uemura, Masanori Ishiguro
Summary: We investigated the effects of dexmedetomidine on excessive glutamate-induced depressions of central excitatory synaptic transmissions in vitro. We found that dexmedetomidine improved the recoveries of depressed synaptic transmissions, providing a protective effect on neuronal dysfunctions induced by excessive glutamate.
Article
Biology
Yuchen Hao, Estelle Toulme, Benjamin Koenig, Christian Rosenmund, Andrew J. R. Plested
Summary: Optical report of neurotransmitter release allows visualization of excitatory synaptic transmission. However, without targeting to synapses, the specificity of the fluorescent signal is uncertain. To address this, the reporter iGluSnFR was fused to glutamate receptor auxiliary proteins to target it to postsynaptic sites. This improved the properties of iGluSnFR and demonstrated the importance of subcellular targeting for optogenetic actuators and reporters.
Review
Neurosciences
Xing Liu, Jun Ying, Xifeng Wang, Qingcui Zheng, Tiancheng Zhao, Sungtae Yoon, Wen Yu, Danying Yang, Yang Fang, Fuzhou Hua
Summary: Astrocytes are major glial cells in the brain, playing a supporting role in the energy and nutritional supply of neurons. They actively regulate synaptic transmission, formation, and plasticity, and any negative changes in their structure or function can impact neuronal activity, leading to neurodevelopmental disorders. Understanding the roles of astrocytes in regulating synaptic development and neural circuit plasticity could lead to new treatments for various neurological and psychiatric disorders.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(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
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
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.
