Article
Pharmacology & Pharmacy
Skyler Younger, Sydney Boutros, Francesca Cargnin, Shin Jeon, Jae W. Lee, Soo-Kyung Lee, Jacob Raber
Summary: FOXG1 syndrome is a rare and devastating neurodevelopmental disorder characterized by various symptoms. Mouse models with Foxg1 gene mutation displayed phenotypes similar to symptoms of human FS individuals, including anxiety, cognitive impairments, and fear memory deficits.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Kirsty R. Erickson, Rebekah Farmer, Jonathan K. Merritt, Zeljka Miletic Lanaghan, Mark D. Does, Karthik Ramadass, Bennett A. Landman, Laurie E. Cutting, Jeffrey L. Neul
Summary: FOXG1 Syndrome is a severe neurodevelopmental disorder caused by a mutation in the FOXG1 gene. Current treatments only alleviate symptoms, but studies on other genetic neurodevelopmental disorders have shown that postnatal expression of gene products can modify the disease course. The researchers generated a mouse model with disrupted protein expression of Foxg1 and found that it displayed behavioral and structural brain phenotypes similar to people with FOXG1 Syndrome. This provides a framework for future studies on post-natal expression of FoxG1 for modifying the disease course.
Article
Multidisciplinary Sciences
Jun Takai, Takashi Shimada, Tadaho Nakamura, James Douglas Engel, Takashi Moriguchi
Summary: Research on Gata2-heterozygous mutant mice showed that these mice had weakened inflammatory responses with reduced levels of certain inflammatory cytokines, particularly IFN-gamma, IL-12p40, and IL-17A, during acute inflammation induced by lipopolysaccharide. As a result, bacterial clearance was significantly impaired in these mice after polymicrobial peritonitis. These findings provide direct insights into how GATA2 affects host defenses and the pathogenic mechanisms related to immunodeficiencies in GATA2-haploinsufficient patients.
Article
Computer Science, Artificial Intelligence
Alain Oros-Gonzalez, Roberto E. Mercadillo, Ricardo Mosco-Aquino, Nayeli Paez-Martinez
Summary: This study demonstrates that environmental enrichment (EE) can effectively attenuate toluene-induced behavioral sensitization. Specifically, exercise and social interaction were identified as the key elements of EE that contributed to this attenuation.
Article
Neurosciences
Junhyung Kim, Junyeop Daniel Roh, Seongbin Kim, Hyojin Kang, Mihyun Bae, Eunjoon Kim
Summary: Slc6a20a deficiency leads to differential changes in behavior and transcriptomes in mice.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Mohamed Darwish, Satoko Hattori, Hirofumi Nishizono, Tsuyoshi Miyakawa, Nozomu Yachie, Keizo Takao
Summary: GlyR alpha 4 subunit is mainly expressed in the hindbrain and midbrain of mice, and has lower expression in other regions of the brain. The expression of GlyR alpha 4 increases during brain development. Mutant mice with Glra4 deficiency show changes in startle response, social behavior, and anxiety-like behavior.
Article
Pharmacology & Pharmacy
Daiki Ueda, Naomi Yonemochi, Tomohiro Kamata, Masahiro Shibasaki, Junzo Kamei, John L. Waddington, Hiroko Ikeda
Summary: This study found that social novelty preference was impaired in diabetic mice, and NPY neurons may be activated in diabetic mice, impairing social novelty preference by promoting glutamatergic function through Y-2 receptors.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Neurosciences
Chung-Pin Hsieh, Shao-Tsu Chen, Mei-Yi Lee, Chieh-Min Huang, Hwei-Hsien Chen, Ming-Huan Chan
Summary: The study found that co-treatment with N,N-dimethylglycine (DMG) and ketamine could prevent the behavioral and synaptic deficits caused by repeated ketamine exposure, paving the way for developing a combination formula for treating depression.
Article
Immunology
Ling Yan, Min-Qing Gu, Zhi-You Yang, Juan Xia, Peng Li, Eero Vasar, Li Tian, Cai Song
Summary: The study reveals that depression is associated with abnormal lipid metabolism, and treatment with Ω-3 PUFAs can effectively alleviate depression by restoring lipid metabolism and suppressing inflammatory response.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Biochemistry & Molecular Biology
Noelia Sofia de Leon Reyes, Paula Sierra Diaz, Ramon Nogueira, Antonia Ruiz-Pino, Yuki Nomura, Christopher A. de Solis, Jay Schulkin, Arun Asok, Felix Leroy
Summary: Adult rodents prefer to interact with novel members of the same species rather than familiar ones. This study identifies neurons in the infra limbic area (ILA) of the mouse prefrontal cortex that express corticotropin-releasing hormone (CRH) and project to the dorsal region of the rostral lateral septum (rLS). The release of CRH during familiar encounters disinhibits rLS neurons, suppressing social interactions with familiar mice and contributing to the preference for social novelty.
Article
Biochemistry & Molecular Biology
Huayue Liu, Xiaowen Meng, Yixuan Li, Shiwen Chen, Yumeng Ji, Shaoyong Song, Fuhai Ji, Xin Jin
Summary: This study investigated the effects of sevoflurane anesthesia in neonatal mice on social behavior. The results showed that mice undergoing sevoflurane anesthesia exhibited strong social capabilities and weak preference for social novelty in their juvenile age. In early adulthood, male mice recovered normal preference for social novelty, while female mice continued to show weak preference. The anesthesia also decreased the expression of PSD95 in the hippocampus of neonatal mice.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Clinical Neurology
Wen-Jie Bian, Oscar C. Gonzalez, Luis de Lecea
Summary: This study reveals that the R1117X mutation in the Shank3 gene causes sleep defects in adolescent mice, which are associated with adult social behavior. The mutant mice exhibit altered electroencephalogram power and increased dopamine activity during REM sleep. These findings provide insights into the relationship between Shank3 gene involvement and sleep phenotypes in schizophrenia.
Article
Biology
Marie Francois, Isabella Canal Delgado, Nikolay Shargorodsky, Cheng-Shiun Leu, Lori Zeltser
Summary: Stress often affects eating behaviors, but the determinants of stress-induced eating are not well understood. This study aims to explore better ways to induce anxiety and evaluate feeding behavior in mice, in order to reliably elicit stress eating. By adjusting experimental conditions such as conducting experiments at night and using overweight mice, the study aims to create an experimental model that closely resembles the physiological conditions in humans.
Article
Immunology
Barakat Alrashdi, Bassel Dawod, Sabine Tacke, Stefanie Kuerten, Patrice D. Cote, Jean S. Marshall
Summary: Nav1.6 plays a crucial role in EAE, and reducing Nav1.6 levels improves motor capacity and reduces inflammatory responses, demonstrating its impact on innate immune response.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Neurosciences
Barbara Rani, Andrea Santangelo, Adele Romano, Justyna Barbara Koczwara, Marzia Friuli, Gustavo Provensi, Patrizio Blandina, Maurizio Casarrubea, Silvana Gaetani, Maria Beatrice Passani, Alessia Costa
Summary: This study investigated the role of brain histamine and its interaction with OEA in response to chronic social defeat stress, a protocol widely used in depression research. The findings confirm the central role of the neurotransmitter histamine as a modulator of complex behavioral responses and suggest that OEA may have protective effects against social stress consequences in a histamine dependent manner.
NEUROBIOLOGY OF STRESS
(2021)
Article
Psychiatry
Hiroko Kotajima-Murakami, Hideo Hagihara, Atsushi Sato, Yoko Hagino, Miho Tanaka, Yoshihisa Katoh, Yasumasa Nishito, Yukio Takamatsu, Shigeo Uchino, Tsuyoshi Miyakawa, Kazutaka Ikeda
Summary: This study found that exposure to the GABA(A) receptor antagonist picrotoxin during the embryonic period induced ASD-like behavior in mice. The offspring exhibited a reduction in active interaction time in social interaction tests, and gene expression analysis showed an increase in odorant receptor gene expression. The findings suggest that impaired odorant function may contribute to social deficits in individuals with ASD.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Takafumi Kawai, Hirotaka Narita, Kohtarou Konno, Sharmin Akter, Rizki Tsari Andriani, Hirohide Iwasaki, Shoji Nishikawa, Norihiko Yokoi, Yuko Fukata, Masaki Fukata, Pattama Wiriyasermkul, Pornparn Kongpracha, Shushi Nagamori, Keizo Takao, Tsuyoshi Miyakawa, Manabu Abe, Kenji Sakimura, Masahiko Watanabe, Atsushi Nakagawa, Yasushi Okamura
Summary: Voltage-sensing protein TMEM266 has a unique voltage-sensing mechanism and interacts with specific splice variants. The coiled-coil region plays a significant role in forming homodimers, and the cytosolic region at the C-terminal of TMEM266 may bind to various targets. TMEM266 deficiency is associated with behavioral abnormalities.
BIOCHEMICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Katsuya Miyajima, Yusuke Sudo, Sho Sanechika, Yoshitaka Hara, Mieko Horiguchi, Feng Xu, Minori Suzuki, Satoshi Hara, Koichi Tanda, Ken-ichi Inoue, Masahiko Takada, Nozomu Yoshioka, Hirohide Takebayashi, Masayo Mori-Kojima, Masahiro Sugimoto, Chiho Sumi-Ichinose, Kazunao Kondo, Keizo Takao, Tsuyoshi Miyakawa, Hiroshi Ichinose
Summary: Increasing evidence suggests that peripheral amino acid metabolism is involved in the pathophysiology of neuropsychiatric disorders, but the molecular mechanisms are largely unknown. This study found that disturbances in tetrahydrobiopterin (BH4) metabolism can lead to hyperphenylalaninemia and monoamine deficiency in the brain, potentially contributing to the development of anxiety-related psychiatric disorders.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Neurosciences
Akiko Oota-Ishigaki, Keizo Takao, Daisuke Yamada, Masayuki Sekiguchi, Masayuki Itoh, Yumie Koshidata, Manabu Abe, Rie Natsume, Masaki Kaneko, Toma Adachi, Toshie Kaizuka, Nami Suzuki, Kenji Sakimura, Hiroyuki Okuno, Keiji Wada, Masayoshi Mishina, Tsuyoshi Miyakawa, Takashi Hayashi
Summary: This study suggests that impairment of AMPA receptor palmitoylation specifically causes symptoms resembling posttraumatic stress disorder (PTSD), including prolonged contextual fear memory formation and increased fear generalization. However, this mutation has no effect on anxiety levels, locomotion, sociability, depression-related behaviors, and spatial learning and memory.
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Developmental Biology
Takayuki Mitsuhashi, Satoko Hattori, Kimino Fujimura, Shinsuke Shibata, Tsuyoshi Miyakawa, Takao Takahashi
Summary: Valproic acid (VPA) is an antiepileptic drug that inhibits epileptic activity of neurons mainly through sodium channel inhibition and GABA transaminase inhibition. It also inhibits histone deacetylases, leading to epigenetic modifications of stem/progenitor cell characteristics and affecting fetal development. Clinical studies have shown that VPA exposure in utero increases the risk of autistic features and intellectual disabilities in children. A study on mice revealed that in utero VPA exposure led to abnormal social interaction, cognitive changes, hypersensitivity to pain/heat, and impaired locomotor activity, resembling symptoms of autism spectrum disorder in humans.
DEVELOPMENTAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Shohei Iida, Hirotaka Shoji, Fumihiro Kawakita, Takehisa Nakanishi, Yoshiaki Matsushima, Makoto Kondo, Koji Habe, Hidenori Suzuki, Tsuyoshi Miyakawa, Keiichi Yamanaka
Summary: Intense itching reduces the quality of life and is associated with psychiatric conditions. This study used a dermatitis mouse model to evaluate psychiatric symptoms and found that Lcn2 is closely associated with anxiety symptoms, but anxiety and depression caused by chronic skin inflammation may be irreversible. Active control of skin inflammation is essential for preventing anxiety.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Hirotaka Shoji, Kazutaka Ikeda, Tsuyoshi Miyakawa
Summary: This study investigated the effects of 5-HTT deficiency on behavior, gut microbiota, and brain c-Fos expression. The findings revealed abnormal behaviors including decreased locomotor activity, reduced pain sensitivity, increased anxiety and depression-related behavior, and altered gut microbiota composition in 5-HTT-/- mice. The expression of c-Fos in certain brain regions was also different from normal. These results indicate that 5-HTT-/- mice serve as a valid animal model to study anxiety and depression.
Article
Neurosciences
Mohamed Darwish, Satoko Hattori, Hirofumi Nishizono, Tsuyoshi Miyakawa, Nozomu Yachie, Keizo Takao
Summary: GlyR alpha 4 subunit is mainly expressed in the hindbrain and midbrain of mice, and has lower expression in other regions of the brain. The expression of GlyR alpha 4 increases during brain development. Mutant mice with Glra4 deficiency show changes in startle response, social behavior, and anxiety-like behavior.
Article
Psychiatry
Hideo Hagihara, Tomoyuki Murano, Tsuyoshi Miyakawa
Summary: The study suggests that changes in brain pH, expressed as pH, are associated with various neuropsychiatric disorders. The expression patterns of pH-associated genes in these disorders were analyzed in human patients and mouse models, showing abnormal expression levels. Furthermore, astrocytes were identified as the cell type with the highest acidity-related gene expression. These findings indicate that the expression pattern of pH-associated genes may serve as a surrogate for pH changes in brain cells and provide insights into the pathophysiology of neuropsychiatric disorders.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Yashuang Ping, Kenji Ohata, Kenji Kikushima, Takumi Sakamoto, Ariful Islam, Lili Xu, Hengsen Zhang, Bin Chen, Jing Yan, Fumihiro Eto, Chiho Nakane, Keizo Takao, Tsuyoshi Miyakawa, Katsuya Kabashima, Miho Watanabe, Tomoaki Kahyo, Ikuko Yao, Atsuo Fukuda, Koji Ikegami, Yoshiyuki Konishi, Mitsutoshi Setou
Summary: As an important neurotransmitter, glutamate functions in the majority of excitatory synapses in the human brain. The metabolic pathway of glutamate is complex, and the exact role of glutamate pool in neurons remains unclear. This study utilized Ttll1 and Ttll7 knockout mice to investigate the impact of tubulin polyglutamylation on neuronal behavior. Matrix-assisted laser desorption/ionization (MALDI) Imaging mass spectrometry (IMS) analysis revealed increased levels of glutamate in the brains of knockout mice, suggesting that tubulin polyglutamylation by TTLLs acts as a reservoir of glutamate in neurons and modulates other glutamate-related amino acids.
Article
Neurosciences
Hirotaka Shoji, Hiroshi Kunugi, Tsuyoshi Miyakawa
Summary: This study investigated the acute and chronic effects of oral administration of capric acid (C10) on behavior in mice. The results showed that high doses of C10 decreased body weight, distance traveled, and increased anxiety-like behavior, while low doses of C10 increased distance traveled. Repeated administration of C10 at a high dose for more than 21 days led to lower body weight and decreased depression-related behavior.
NEUROPSYCHOPHARMACOLOGY REPORTS
(2022)
Meeting Abstract
Ophthalmology
Chieko Koike, Tesshu Hori, Keishun Iwao, Shohei Ikuta, Satoko Hattori, Keizo Takao, Tsuyoshi Miyakawa
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Clinical Neurology
Masayoshi Nagai, Kenji Iemura, Takako Kikkawa, Sharmin Naher, Satoko Hattori, Hideo Hagihara, Koh-ichi Nagata, Hayato Anzawa, Risa Kugisaki, Hideki Wanibuchi, Takaya Abe, Kenichi Inoue, Kengo Kinoshita, Tsuyoshi Miyakawa, Noriko Osumi, Kozo Tanaka
Summary: The deficiency of CHAMP1 gene causes intellectual disability and is associated with delayed neuronal development and behavioral defects observed in mice models.
BRAIN COMMUNICATIONS
(2022)