Article
Neurosciences
Alibek Kuanyshbek, Meng Wang, Asa Andersson, Marie Tuifua, Elizabeth E. Palmer, Rani K. Sachdev, Ting-Wei Mu, Irina Vetter, Angelo Keramidas
Summary: This research identified a new variant of GABAA receptor associated with seizures and studied its pathogenicity and response to anti-seizure drugs. The study found that the variant reduced receptor surface trafficking and peak GABA-gated currents, leading to shorter receptor activity duration. However, certain anti-seizure drugs were able to enhance the variant receptor expression and restore receptor function.
Article
Neurosciences
B. Spurny, T. Vanicek, R. Seiger, M. B. Reed, M. Kloebl, V Ritter, J. Unterholzner, G. M. Godbersen, L. R. Silberbauer, D. Pacher, S. Klug, M. E. Konadu, G. Gryglewski, S. Trattnig, W. Bogner, R. Lanzenberger
Summary: The study focused on investigating the effects of associative relearning and SSRI treatment on GABAergic and glutamatergic function, revealing a significant interaction effect on hippocampal and thalamic Glx/tCr levels following SSRI treatment.
Article
Biochemistry & Molecular Biology
Chunmei Zeng, Danqing Lei, Yuling Lu, Qi Huang, Ying Wu, Shengyu Yang, Yuan Wu
Summary: The aim of this study was to modify the parvalbumin gene expression in PC12 cells and investigate its influence on the metabolic pathway involving glutamate and GABA. The expression of parvalbumin was found to be associated with GAD65 and GAD67. Overexpression of parvalbumin up-regulated GAD65 and GAD67, increased GABA levels, and decreased glutamate levels, while silencing parvalbumin had the opposite effects.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Toshikazu Kakizaki, Tomokazu Ohshiro, Makoto Itakura, Kohtarou Konno, Masahiko Watanabe, Hajime Mushiake, Yuchio Yanagawa
Summary: GAD65 deficiency causes different phenotypes between rats and mice, with Gad2(-/-) rats being more severely affected and exhibiting more severe symptoms such as epilepsy and premature death. Considering the similarity of GAD65/GAD67 ratio in human brains to that in rat brains, Gad2(-/-) rats would be useful for further investigating the roles of GAD65 in vivo.
Article
Pharmacology & Pharmacy
Martina Tallarico, Antonio Leo, Emilio Russo, Rita Citraro, Ernesto Palma, Giovambattista De Sarro
Summary: Autism spectrum disorders (ASDs) and epilepsy show a bidirectional link, possibly through common neurobiological pathways. BTBR mice have increased susceptibility to seizures induced by chemoconvulsants impairing GABA(A) neurotransmission, while there is no significant difference for seizures induced by AMPA, NMDA, and Kainate. PTZ-kindling does not affect autistic-like behavior in BTBR mice but can increase anxiety and worsen cognitive performance. This suggests a tight connection between ASD and epilepsy.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Clinical Neurology
Dongyu Liu, Kazuyuki Fujihara, Yuchio Yanagawa, Hajime Mushiake, Tomokazu Ohshiro
Summary: By recording EEG in knockout rats for Gad1, we found that GABA can both suppress and enhance SWD generation. Comparison between normal rats and Gad1 knockout rats revealed that SWD symptoms were more severe in Gad1 knockout rats, and the effects of valproate treatment differed in the two groups. Immunohistochemistry results indicated significantly reduced GABA immunoreactivity in the RTN neurons of Gad1 knockout rats.
FRONTIERS IN NEUROLOGY
(2023)
Article
Neurosciences
Connor D. Courtney, Courtney Sobieski, Charu Ramakrishnan, Robbie J. Ingram, Natalia M. Wojnowski, R. Anthony DeFazio, Karl Deisseroth, Catherine A. Christian-Hinman
Summary: Astrocytes play a crucial role in modulating synaptic transmission and can respond to local synaptic activity. Researchers have used a viral vector called Opto alpha 1AR to selectively activate G protein signaling pathways in astrocytes. It was found that high-frequency light stimulation of Opto alpha 1AR can increase both inhibitory and excitatory synaptic currents, while low-frequency stimulation does not have the same effect. This study highlights the importance of temporal dynamics in manipulating astrocyte function using optical tools.
Article
Clinical Neurology
Philip K. Ahring, Vivian W. Y. Liao, Elena Gardella, Katrine M. Johannesen, Ilona Krey, Kaja K. Selmer, Barbro F. Stadheim, Hannah Davis, Charlotte Peinhardt, Mahmoud Koko, Rohini K. Coorg, Steffen Syrbe, Astrid Bertsche, Teresa Santiago-Sim, Tue Diemer, Christina D. Fenger, Konrad Platzer, Evan E. Eichler, Holger Lerche, Johannes R. Lemke, Mary Chebib, Rikke S. Moller
Summary: This study identified variants in the GABRD gene that are associated with neurodevelopmental disorders and epilepsy. These variants alter the function of GABA receptors and are closely related to the clinical phenotypes of the affected individuals. The findings suggest that gain-of-function variants lead to symptoms such as neurodevelopmental disorders, epilepsy, and cognitive impairment, while loss-of-function variants are associated with autism spectrum disorder.
Article
Neurosciences
Rodrigo Ribeiro dos Santos, Tulio C. Bernardino, Maria Carolina Machado da Silva, Antonio C. P. de Oliveira, Luciana E. Drumond, Daniela Rosa, Andre R. Massensini, Marcio F. D. Moraes, Maria C. Doretto, Marco A. Romano-Silva, Helton J. Reis
Summary: In this study, using WAR model, significant alterations in glutamatergic and GABAergic pathways, as well as increased expression of NCS-1 in the hippocampus and inferior colliculus were observed. These changes may be associated with hyperexcitability propagation and recruitment of multiple brain regions.
NEUROSCIENCE LETTERS
(2021)
Article
Neurosciences
Viktoria S. Pendeliuk, Igor V. Melnick
Summary: Synchronization of hippocampal interneurons (INs) relies on local cell interactions and intensity of network activity. In baseline conditions, a significant portion of inhibitory postsynaptic currents coincided between cells. Network activity induced excitatory and inhibitory events, with excitatory events capable of synchronizing IN firing. Glutamatergic mechanisms play a crucial role in initiating and dominating IN synchronization.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Biology
Gabriele Ruffolo, Alessandro Gaeta, Beatrice Cannata, Camilla Pinzaglia, Eleonora Aronica, Alessandra Morano, Pierangelo Cifelli, Eleonora Palma
Summary: The potential use of phytocannabinoids (pCBs), specifically cannabidiol (CBD), to treat pathological conditions has gained attention in the scientific community. CBD has shown the ability to modulate GABAergic neurotransmission and may be effective in treating pharmaco-resistant epilepsy.
Article
Clinical Neurology
Emi Nakamura-Maruyama, Risa Kai, Naoyuki Himi, Naohiko Okabe, Kazuhiko Narita, Tetsuji Miyazaki, Shozo Aoki, Osamu Miyamoto
Summary: This study found that the protein expressions of RyR1 and RyR3 significantly increased in the hippocampus of mouse models with depression-like symptoms, and ECS therapy could attenuate this increase and improve depression symptoms. However, pre-injection with RyRs blocker dantrolene reduced the antidepressant effects of ECS.
Article
Multidisciplinary Sciences
Masato Kinboshi, Saki Shimizu, Kentaro Tokudome, Tomoji Mashimo, Tadao Serikawa, Hidefumi Ito, Ryosuke Takahashi, Akio Ikeda, Yukihiro Ohno
Summary: Mutations in the Lgi1 gene cause changes in neurotransmission, with increased glutamate release and reduced GABA release. These alterations may be associated with susceptibility to audiogenic seizures.
Article
Biochemistry & Molecular Biology
Anna A. Kovalenko, Maria V. Zakharova, Alexander P. Schwarz, Alexandra V. Dyomina, Olga E. Zubareva, Aleksey V. Zaitsev
Summary: This study analyzed the changes in gene expression of mGluR subtypes in different brain regions during the latent and chronic phases of a lithium-pilocarpine model of epilepsy. The results showed region- and phase-specific changes in expression, with increased mGluR5 mRNA levels and decreased expression of group III genes during the latent phase. Most of the changes in expression detected in the latent stage were absent in the chronic stage, except for reduced mGluR8 mRNA production in the hippocampus. The study suggested that agonists of group III mGluRs are the most promising targets for preventing epilepsy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Falko Lange, Julia Hoernschemeyer, Timo Kirschstein
Summary: The progression of glioblastomas and tumor-associated epilepsy is closely linked through various pathophysiological mechanisms involving the neurotransmitter glutamate. Current research focuses on the role of glutamate receptors in these diseases and discusses future interventions to interfere with the glutamatergic network.
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
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
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.