Article
Psychiatry
Toral S. Surti, Mohini Ranganathan, Jason K. Johannesen, Ralitza Gueorguieva, Emma Deaso, Joshua G. Kenney, John H. Krystal, Deepak Cyril D'Souza
Summary: This study aimed to investigate the synergistic effects of a GLYT1 inhibitor and computerized cognitive training (CT) on cognitive impairments associated with schizophrenia (CIAS). However, the results showed that the combination of GLYT1 inhibitor with CT did not lead to greater improvement in CIAS compared to CT alone.
SCHIZOPHRENIA RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Daniel C. Javitt
Summary: Cognitive impairment is a prominent feature of schizophrenia, and its assessment methods are well established. The role of social cognitive impairment and sensory-level dysfunction in functional outcomes has also been recognized. Treatment development targeting N-methyl-d-aspartate receptor (NMDAR) and its associated impairments has become encouraging. Mismatch negativity has emerged as a promising biomarker for early-stage drug development in schizophrenia.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2023)
Article
Chemistry, Medicinal
Pieter H. Bos, Evelyne M. Houang, Fabio Ranalli, Abba E. Leffler, Nicholas A. Boyles, Volker A. Eyrich, Yuval Luria, Dana Katz, Haifeng Tang, Robert Abel, Sathesh Bhat
Summary: The lead optimization stage of a drug discovery program involves the design, synthesis, and testing of numerous compounds. However, there are limitations to this process, including the difficulty of rapidly designing potent molecules and exploring a vast chemical space. To address these limitations, researchers have developed AutoDesigner, a novel algorithm that can generate and optimize millions to billions of virtual molecules while adhering to specific project criteria. The algorithm only requires a starting ligand and a binding model, making it suitable for early stages of drug discovery. The effectiveness of AutoDesigner was demonstrated by successfully designing novel inhibitors for d-amino acid oxidase and meeting various project goals.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Review
Neurosciences
Sam A. Booker, David J. A. Wyllie
Summary: NMDARs are essential for synaptic information transfer and plasticity in the majority of brain circuits. Inhibitory GABAergic interneurons exhibit diverse NMDAR expression and function, controlling cellular excitation in a synapse-specific manner. Further research is needed to fully understand the role of NMDARs in modulating GABAergic synaptic and circuit function.
Review
Biochemistry & Molecular Biology
Chitra Vinnakota, Matthew R. R. Hudson, Nigel C. C. Jones, Suresh Sundram, Rachel A. A. Hill
Summary: Glutamate N-methyl-D-aspartate receptor (NMDAR) hypofunction is believed to be responsible for schizophrenia symptoms. Among the NMDAR subunits, the GluN2D subunit is implicated in schizophrenia-related phenotypes, and further research into this subunit may lead to novel therapeutic targets for the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Psychiatry
Kasumi Yasuda, Shinya Uenishi, Hiroshi Sakamoto, Kohei Hori, Jinsoo Koh, Shun Takahashi
Summary: This article presents a case of a woman diagnosed with schizophrenia without antiNMDAR antibodies after experiencing NMDAR encephalitis. The study suggests that NMDAR dysfunction may be associated with the onset of schizophrenia.
ASIAN JOURNAL OF PSYCHIATRY
(2022)
Article
Pharmacology & Pharmacy
Serena Deiana, Wolfgang Hauber, Alexandra Munster, Susanne Sommer, Boris Ferger, Anelise Marti, Bernhard Schmid, Cornelia Dorner-Ciossek, Holger Rosenbrock
Summary: This study suggests that the GlyT1 inhibitor Bitopertin improves cognition and certain symptoms associated with schizophrenia, such as memory deficits, by increasing glycine levels. These findings may have important clinical implications for the treatment of diseases characterized by NMDR hypofunction, such as schizophrenia.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Tonghui Su, Yi Lu, Chaoying Fu, Yang Geng, Yelin Chen
Summary: This study demonstrates that the loss of GluN2A in adult mouse brains can elicit strong antidepressant-like responses without causing psychomimetic effects similar to Ketamine. The antidepressant effects of Ketamine and MK-801 are mainly mediated by the suppression of GluN2A rather than GluN2B.
NATURE NEUROSCIENCE
(2023)
Article
Neurosciences
Tonghui Su, Yi Lu, Chaoying Fu, Yang Geng, Yelin Chen
Summary: The study found that the loss of GluN2A in adult mice elicits antidepressant-like responses without causing psychomimetic effects similar to ketamine. The antidepressant effects of ketamine and MK-801 are mediated by the suppression of GluN2A, not GluN2B. Additionally, these drugs increase the excitability of hippocampal neurons through GluN2A.
NATURE NEUROSCIENCE
(2023)
Article
Medicine, Research & Experimental
Mihyun Bae, Junyeop Daniel Roh, Youjoung Kim, Seong Soon Kim, Hye Min Han, Esther Yang, Hyojin Kang, Suho Lee, Jin Yong Kim, Ryeonghwa Kang, Hwajin Jung, Taesun Yoo, Hyosang Kim, Doyoun Kim, Heejeong Oh, Sungwook Han, Dayeon Kim, Jinju Han, Yong Chul Bae, Hyun Kim, Sunjoo Ahn, Andrew M. Chan, Daeyoup Lee, Jin Woo Kim, Eunjoon Kim
Summary: Research has shown that SLC6A20A is an amino acid transporter that regulates proline and glycine balance in the brain and NMDAR function. Mutant PTEN protein may enhance abnormal expression of SLC6A20A transcript and protein by increasing binding to the Slc6a20a gene. Modulating SLC6A20A can normalize NMDAR currents and restore behavior in mice.
EMBO MOLECULAR MEDICINE
(2021)
Article
Neurosciences
Rongjun Liu, Daofan Sun, Xiuzhong Xing, Qingge Chen, Bo Lu, Bo Meng, Hui Yuan, Lan Mo, Liufang Sheng, Jinwei Zheng, Qiusheng Wang, Junping Chen, Xiaowei Chen
Summary: The coexistence of pain and depression is frequently observed in patients with chronic pain and depression. Oxytocin, a neuropeptide, has been reported to relieve chronic pain and depressive symptoms. This study investigated the effect of intranasal oxytocin on neuropathic pain and comorbid depressive symptoms, and found that oxytocin attenuated depression-like behavior but did not alleviate mechanical hyperalgesia. The results suggest that intranasal oxytocin may have the potential to treat depressive symptoms in neuropathic pain patients.
Article
Biochemistry & Molecular Biology
Kayla Farrell, Madeline Musaus, Aubrey Auerbach, Shaghayegh Navabpour, W. Keith Ray, Richard F. Helm, Timothy J. Jarome
Summary: Females have higher levels of proteasome-independent K63-polyubiquitination in the amygdala following fear conditioning, which is involved in regulating ATP synthesis and proteasome activity. Knockdown of K63-polyubiquitination impairs fear memory and reduces ATP levels and proteasome activity in female rats, but not in males. These findings provide the first evidence linking proteasome-independent and proteasome-dependent UPS functions in fear memory formation and may contribute to understanding the sex differences in PTSD development.
MOLECULAR PSYCHIATRY
(2023)
Article
Cell Biology
Tatyana Y. Postnikova, Dmitry V. Amakhin, Alina M. Trofimova, Natalia L. Tumanova, Nadezhda M. Dubrovskaya, Daria S. Kalinina, Anna A. Kovalenko, Anastasiia D. Shcherbitskaia, Dmitry S. Vasilev, Aleksey V. Zaitsev
Summary: Maternal hyperhomocysteinemia during pregnancy leads to memory impairments in rats, associated with reduced long-term potentiation (LTP) and altered NMDA receptor desensitization in the hippocampus. Expression of glutamate receptor subunits is unaffected except for GluN1. Additionally, delayed hippocampal maturation and decreased synaptopodin-positive spines were observed in offspring.
Article
Biochemistry & Molecular Biology
Sighild Lemarchant, Melissa Sourioux, Juliette Le Douce, Alexandre Henriques, Noelle Callizot, Sandrine Hugues, Melissa Farinelli, Yann Godfrin
Summary: NX210c enhances excitatory synaptic currents and synaptic transmission in the brain, leading to improved memory. By modulating synaptic transmission and signaling, NX210c presents an innovative therapeutic opportunity for neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Tatyana Y. Postnikova, Alina M. Trofimova, Maria Zakharova, Olga Nosova, Alexey R. Brazhe, Dmitry E. Korzhevskii, Alexey Semyanov, Aleksey Zaitsev
Summary: This study examined the long-term effects of pentylenetetrazole-induced generalized seizures in three-week-old rats. The seizures resulted in neuronal loss in several hippocampal regions and impaired long-term synaptic potentiation. The mechanism of plasticity induction was altered, and the function of core-located NMDA receptors was weakened, likely due to disturbed glutamate clearance from the synaptic cleft.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Ailin Luo, Zifeng Wu, Shan Li, Cindy B. McReynolds, Di Wang, Hanyu Liu, Chaoli Huang, Teng He, Xinying Zhang, Yuanyuan Wang, Cunming Liu, Bruce D. Hammock, Kenji Hashimoto, Chun Yang
Summary: This study investigated the relationship between chronic pain and depression and the potential benefits of inhibiting soluble epoxide hydrolase (sEH) signaling. The results showed that sEH expression was associated with pain and depression behaviors, and the sEH inhibitor TPPU improved the symptoms of both. The therapeutic effects of TPPU were mediated through the AHR and TSPO signaling pathways.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Neurosciences
Zhiqian Yu, Kazuko Ueno, Ryo Funayama, Mai Sakai, Naoki Nariai, Kaname Kojima, Yoshie Kikuchi, Xue Li, Chiaki Ono, Junpei Kanatani, Jiro Ono, Kazuya Iwamoto, Kenji Hashimoto, Kengo Kinoshita, Keiko Nakayama, Masao Nagasaki, Hiroaki Tomita
Summary: This study investigated the transcriptional profiles in the dorsolateral prefrontal cortex (DLPFC) to understand the clinical and biological differences of schizophrenia between males and females. The results showed that females with schizophrenia had more significantly changed genes compared to males, and these changes were mainly related to mitochondrial, ATP- and metal ion-binding relevant biological processes. The differentially expressed genes related to schizophrenia in females were involved in midbrain dopaminergic and GABA-ergic neurons and microglia. Additionally, analysis of a murine model revealed that the methylation and transcriptional expression of the ACSBG1 locus potentially impact the sex differences in gene transcription.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jie Guo, Di Qiu, Han-wen Gu, Xing-ming Wang, Kenji Hashimoto, Guang-fen Zhang, Jian-jun Yang
Summary: The perioperative administration of ketamine reduces postoperative depression and pain scores but increases the risk of adverse effects.
MOLECULAR PSYCHIATRY
(2023)
Article
Neurosciences
Xingming Wang, Akifumi Eguchi, Yong Yang, Lijia Chang, Xiayun Wan, Jiajing Shan, Youge Qu, Li Ma, Chisato Mori, Jianjun Yang, Kenji Hashimoto
Summary: Multiple sclerosis (MS) is a common demyelinating disease that affects the central nervous system. This study investigated the effects of subdiaphragmatic vagotomy (SDV) on demyelination in cuprizone (CPZ)-treated mice and found that SDV significantly improved demyelination and microglial activation in the brain. Analysis of gut microbiota composition and blood metabolites revealed that SDV also improved the abnormal levels in CPZ-treated mice. These findings suggest a link between the gut microbiota-brain axis and demyelination in the brain.
NEUROBIOLOGY OF DISEASE
(2023)
Correction
Neurosciences
X. Wang, A. Eguchi, Y. Yang, L. Chang, X. Wan, J. Shan, Y. Qu, L. Ma, C. Mori, J. Yang, K. Hashimoto
NEUROBIOLOGY OF DISEASE
(2023)
Article
Behavioral Sciences
Youge Qu, Lijia Chang, Li Ma, Xiayun Wan, Kenji Hashimoto
Summary: This study compared the effects of hallucinogenic psychedelic drug DOI, non-hallucinogenic psychedelic analog lisuride, and novel antidepressant (R)-ketamine on depression-like behavior and dendritic spine density in the brain. It was found that lisuride and (R)-ketamine improved these changes, while DOI did not. This suggests that the antidepressant-like effect of lisuride is not associated with 5-HT2AR-related psychedelic effects.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2023)
Editorial Material
Neurosciences
Kenji Hashimoto, Shigeyuki Chaki
Article
Neurosciences
Xiao-Hui Tang, Yu-Gang Diao, Zhuo-Yu Ren, Yan-Yu Zang, Guang-Fen Zhang, Xing-Ming Wang, Gui-Fang Duan, Jin-Chun Shen, Kenji Hashimoto, Zhi-Qiang Zhou, Jian-Jun Yang
Summary: Mouse models of depression-like behavior showed decreased levels of GABA and increased levels of glutamate in the hippocampus. Ketamine treatment reversed these alterations by increasing GABA levels and decreasing glutamate levels. These effects were mediated by changes in enzymes and transporters on GABAergic neurons and astrocytes.
Article
Neurosciences
Xiayun Wan, Akifumi Eguchi, Lijia Chang, Chisato Mori, Kenji Hashimoto
Summary: Patients with depression often have reduced bone mineral density. The new antidepressant arketamine has been shown to improve this reduction in mice. This study investigates the potential role of the gut microbiota and its metabolites in the beneficial effects of arketamine on behavioral and bone density changes in mice with chronic social defeat stress.
Article
Neurosciences
Yaoyu Pu, Qiuhong Wu, Qiuping Zhang, Tianwen Huang, Ji Wen, Long Wei, Kenji Hashimoto, Yi Liu
Summary: This study aimed to investigate the effect of mesenchymal stem-cell-derived microvesicles (MSC-MVs) in treating Parkinson's disease (PD). The results showed that single administration of MSC-MVs could alleviate the reduction of dopamine transporter and tyrosine hydroxylase expressions in the striatum and substantia nigra (SNr) of mice after MPTP injection. MSC-MVs also restored the abnormal gut microbiota composition induced by MPTP. Therefore, MSC-MVs have a new therapeutic potential for neurological disorders such as PD.
PSYCHOPHARMACOLOGY
(2023)
Article
Immunology
Xiayun Wan, Akifumi Eguchi, Akemi Sakamoto, Yuko Fujita, Yong Yang, Youge Qu, Masahiko Hatano, Chisato Mori, Kenji Hashimoto
Summary: Depletion of gut microbiota induced by antibiotic administration affects spleen and brain function, leading to decreased spleen weight and altered immune cell populations. Depletion of gut microbiota also leads to changes in metabolite levels, affecting spleen and brain function.
BRAIN, BEHAVIOR, & IMMUNITY - HEALTH
(2023)
Review
Biochemistry & Molecular Biology
Kenji Hashimoto
Summary: The COVID-19 pandemic caused by SARS-CoV-2 infection has resulted in various health issues, including persistent neurological and psychiatric symptoms known as long COVID or brain fog. The virus has been detected in the brains of patients who died from COVID-19, and Epstein-Barr virus reactivation and changes in the microbiome may contribute to long COVID symptoms. This article discusses the detrimental effects of COVID-19 on the brain and the biological mechanisms underlying long COVID, as well as potential therapeutic approaches targeting the gut-brain axis.
MOLECULAR PSYCHIATRY
(2023)
Review
Biochemistry & Molecular Biology
Kenji Hashimoto
Summary: The human body contains a diverse ecosystem of microorganisms, known as the microbiota, which includes bacteria, viruses, and fungi. Current research is focusing on the potential association between the microbiota and neuropsychiatric disorders. While the gut microbiota has received particular attention, the microbiota in other body tissues also influences the development and progression of these disorders. This article provides an overview of the role of the host microbiota in neuropsychiatric disorders and explores future research directions.
MOLECULAR PSYCHIATRY
(2023)
Article
Psychiatry
Li Ma, Long Wang, Youge Qu, Xiayun Wan, Kenji Hashimoto
Summary: Relapse is common in remitted patients with major depressive disorder (MDD). Arketamine, an (R)-enantiomer of ketamine, has persistent prophylactic actions in an inflammatory model of depression. The heme biosynthesis II pathway in the spleen could be a new target for the prevention of relapse in MDD patients.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Neurosciences
Yukihiko Shirayama, Masaaki Iwata, Kanako Miyano, Yuki Hirose, Yasunori Oda, Yuko Fujita, Kenji Hashimoto
Summary: Beta-hydroxybutyrate (BHB) has shown antidepressant-like effects in a rat model of depression. It activates the BDNF-TrkB signaling pathway and AMPA receptors, and is associated with the prefrontal cortex, hippocampus, and basolateral region of amygdala.
Article
Clinical Neurology
Hannah Meijs, Helena Voetterl, Alexander T. Sack, Hanneke van Dijk, Bieke De Wilde, Jan Van Hecke, Peter Niemegeers, Evian Gordon, Jurjen J. Luykx, Martijn Arns
Summary: This study used a polygenic score (PGS) and electroencephalography (EEG) data analysis to identify potential predictors for treatment outcomes in major depressive disorder (MDD). The results suggest the existence of a stable EEG network related to antidepressant-response that has potential as a predictor for MDD treatment, particularly in the case of venlafaxine.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2024)