Review
Biochemistry & Molecular Biology
Sarah Larrigan, Sujay Shah, Alex Fernandes, Pierre Mattar
Summary: During brain development, the genome is repeatedly reconfigured to aid neuronal and glial differentiation, with a range of chromatin remodeling complexes facilitating the process. The non-redundancy of these complexes suggests a need for a variety of remodelers with different specificities and activities in neurodevelopment. The nucleosome remodeling and deacetylase (NuRD) complex plays a key role in the biochemistry, genetics, and functions of neural progenitors and neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Chuanchuan Wang, Weixuan Chen, Yishan Jiang, Xiao Xiao, Qianhui Zou, Jiarui Liang, Yu Zhao, Qianxu Wang, Tian Yuan, Rui Guo, Xuebo Liu, Zhigang Liu
Summary: Autism Spectrum Disorder (ASD) symptoms may be improved through modulation of gut microbiota. This study investigated the effects of a synbiotic treatment on an ASD-like mouse model, and found that it rectified social impairments, attenuated inflammatory cytokine expressions, protected gut barrier integrity, and altered gut microbiota composition. The synbiotic treatment elevated beneficial metabolites and upregulated genes associated with their synthesis. Overall, the synbiotic combination mitigated ASD-related social impairments through regulation of the gut-brain axis.
Article
Neurosciences
Soo Yeon Lee, Hanseul Kweon, Hyojin Kang, Eunjoon Kim
Summary: Chd8(+/N2373K) mice display autistic-like behaviors in juvenile and adult males, but not in females. In contrast, Chd8(+/S62X) mice show behavioral deficits in juvenile males and both adult males and females, indicating age-differential sexually dimorphic behaviors. Excitatory synaptic transmission is suppressed and enhanced in male and female Chd8(+/S62X) juveniles, respectively, but similarly enhanced in adult male and female mutants. ASD-like transcriptomic changes are stronger in newborn and juvenile (but not adult) Chd8(+/S62X) males, while in newborn and adult (not juvenile) Chd8(+/S62X) females. These findings suggest age-differential sexual dimorphisms in Chd8(+/S62X) mice at synaptic and transcriptomic levels, in addition to behavioral level.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Immunology
Yi Luo, Keyi Lv, Zhulin Du, Dandan Zhang, Mei Chen, Jing Luo, Lian Wang, Tianyao Liu, Hong Gong, Xiaotang Fan
Summary: Autism spectrum disorder (ASD) lacks effective pharmacological treatments. Minocycline, known for its anti-inflammatory properties and neuroprotective effects, inhibits microglial activation. This study used a mouse model of autism and found that minocycline administration improved ASD-like behaviors, neurogenesis, and inhibited microglia activation. These findings suggest that minocycline supplementation might be a potential strategy for improving ASD symptoms.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Behavioral Sciences
Jacqueline N. Crawley
Summary: More than 100 single gene mutations and copy number variants have been identified as risk factors for autism spectrum disorder. By introducing similar mutations into the genomes of laboratory mice and other species, researchers have been able to understand how each mutation contributes to the development of autism symptoms. Using behavioral assays that mirror the diagnostic criteria for autism, scientists have discovered the behavioral consequences of these mutations in animal models. These findings, along with other measures such as electrophysiology and neuroanatomy, are being used to develop effective therapeutic interventions in translational investigations.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Article
Multidisciplinary Sciences
A. Ayanna Wade, Jelle van den Ameele, Seth W. Cheetham, Rebecca Yakob, Andrea H. Brand, Alex S. Nord
Summary: The study suggests that TaDa-seq is a valuable alternative method for mapping protein-DNA interactions in vivo, providing insights into regulatory targets of CHD8 and autism-related pathophysiology.
Article
Cell Biology
Linn Amanda Syding, Agnieszka Kubik-Zahorodna, Petr Nickl, Vendula Novosadova, Jana Kopkanova, Petr Kasparek, Jan Prochazka, Radislav Sedlacek
Summary: A novel mouse model with a complete deletion of the Ube3a gene exhibits important phenotypes characteristic of Angelman syndrome, including motor dysfunction and behavioral abnormalities.
Article
Biochemistry & Molecular Biology
Giuseppe Pepe, Salvatore Fioriniello, Federico Marracino, Luca Capocci, Vittorio Maglione, Maurizio D'Esposito, Alba Di Pardo, Floriana Della Ragione
Summary: Rett syndrome is a severe neurodevelopmental disorder caused by pathogenetic variants in the MECP2 gene. This study found that Rett syndrome patients have impaired brain vascular homeostasis and blood-brain barrier breakdown, which may contribute to the cognitive impairment. The study provides evidence of impaired blood-brain barrier integrity in Rett syndrome and offers new perspectives for novel therapeutic strategies.
Article
Psychiatry
Ekachaeryanti Zain, Naoki Fukui, Yuichiro Watanabe, Koyo Hashijiri, Takaharu Motegi, Maki Ogawa, Jun Egawa, Koji Nishijima, Toshiyuki Someya
Summary: This study aimed to clarify the optimal factor structure of the AQ for assessing autistic traits among perinatal women in Japan. Through exploratory and confirmatory factor analysis on a sample of Japanese women, a model consisting of 25 items distributed across three factors was identified. This three-factor model was found to be superior to previous models in assessing autistic traits.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Immunology
Marcel van de Wouw, Calum J. Walsh, Giulia M. D. Vigano, Joshua M. Lyte, Marcus Boehme, Andreu Gual-Grau, Fiona Crispie, Aaron M. Walsh, Gerard Clarke, Timothy G. Dinan, Paul D. Cotter, John F. Cryan
Summary: Research shows that Kefir can improve repetitive behavior in a mouse model of autism, enhance immune response, and modulate gut microbiome composition.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Psychiatry
Anita Brito, Felipe Franco, Helena Brentani, Patricia Cristina Baleeiro Beltrao-Braga
Summary: This study collected data on family history and environmental factors from 2,141 individuals with Autism Spectrum Disorders (ASD) in Brazil. Multiple Correspondence Analysis and Cluster Analysis revealed the interplay between genetics and environment. The results showed that genetic background, social and psychological factors played significant roles in ASD, but it was not possible to isolate patients based on genetic vulnerability or environmental exposure. Instead, a continuum of different compositions of genetic and environmental interplay was observed.
Article
Multidisciplinary Sciences
Masud Rabbani, Munirul M. Haque, Dipranjan Das Dipal, Md Ishrak Islam Zarif, Anik Iqbal, Amy Schwichtenberg, Naveen Bansal, Tanjir Rashid Soron, Syed Ishtiaque Ahmed, Sheikh Iqbal Ahamed
Summary: This study aimed to evaluate the behavioral patterns of children with ASD during and after the COVID-19 lockdown, and found that support in the areas of problematic behavior could mitigate future risks.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Nathan McChesney, Jeremy L. Barth, Jeffrey A. Rumschlag, Junying Tan, Adam J. Harrington, Kenyaria V. Noble, Carolyn M. McClaskey, Phillip Elvis, Silvia G. Vaena, Martin J. Romeo, Kelly C. Harris, Christopher W. Cowan, Hainan Lang
Summary: This study reveals the importance of MEF2C function in inner ear development and function, as well as the involvement of immune and non-neuronal cells in auditory nerve dysfunction and ASD-related phenotypes. The findings provide a comprehensive approach to characterizing auditory nerve function in mice and can be applied to other animal models with auditory processing impairments.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Oncology
Hye-Yeon Park, Jun Go, Young-Kyoung Ryu, Dong-Hee Choi, Jung-Ran Noh, Jin-Pyo An, Won-Keun Oh, Pyung-Lim Han, Chul-Ho Lee, Kyoung-Shim Kim
Summary: The study found that Humulus japonicus may have therapeutic potential for ASD, ameliorating behavioral deficits and neuroinflammation in ASD mouse models.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Neurosciences
Soo Yeon Lee, Hanseul Kweon, Hyojin Kang, Eunjoon Kim
Summary: Autism spectrum disorders (ASD) are more common in males than females, and a specific gene mutation has been found to cause male-preponderant autistic-like behaviors in mice during juvenile and adult stages.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
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
Multidisciplinary Sciences
Tomoyuki Murano, Ryuichi Nakajima, Akito Nakao, Nao Hirata, Satoko Amemori, Akira Murakami, Yukiyasu Kamitani, Jun Yamamoto, Tsuyoshi Miyakawa
Summary: The dentate gyrus (DG) plays a critical role in cognitive functions, but its information representation mechanism is not fully understood. In this study, neuronal activity in the DG of freely moving mice was recorded using Ca2+ imaging and analyzed using machine learning. The results showed that multiple types of information can be independently decoded from the activity patterns of DG neurons, and different types of information are encoded by different populations of neurons.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Daiki X. Sato, Yukiko U. Inoue, Nahoko Kuga, Satoko Hattori, Kensaku Nomoto, Yuki Morimoto, Giovanni Sala, Hideo Hagihara, Takefumi Kikusui, Takuya Sasaki, Yuji Ikegaya, Tsuyoshi Miyakawa, Takayoshi Inoue, Masakado Kawata
Summary: This study introduces human-specific mutations into mice and investigates their impact on behavior, neurophysiology, and molecular level. The results show that the introduction of the Ile mutation leads to reduced anxiety-related traits and altered oscillatory activity in the amygdala under anxiogenic conditions. Transcriptome analysis confirms changes in gene expression in the amygdala, further supporting the observed phenotypes.
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)