Article
Biochemistry & Molecular Biology
Ning Li, Shuai Cao, Zengli Yu, Mingwu Qiao, Yongxia Cheng, Yue Shen, Lianjun Song, Xianqing Huang, Guojun Yang, Yali Zhao
Summary: Exposure of mothers to lead in drinking water can alter the expression of Clstn2 and Clstn3 in offspring, leading to learning deficiencies. This study indicates that calsyntenin-2 and calsyntenin-3 may play different roles in synaptic development and differentiation under the influence of lead exposure.
BIOLOGICAL TRACE ELEMENT RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yi Wang, Chunxue Liu, Jingxin Deng, Qiong Xu, Jia Lin, Huiping Li, Meixin Hu, Chunchun Hu, Qiang Li, Xiu Xu
Summary: Hyper-reactivity to sensory inputs is a common symptom of autism spectrum disorder (ASD), but its underlying neural abnormalities are unclear. By studying a zebrafish model with SHANK2 mutations, the study found that the deficiency of SHANK2 contributes to sensory abnormalities and ASD-like behaviors. The model exhibited reduced social preference, enhanced behavioral stereotypy, hyper-sensitivity to auditory noise, and abnormal hyperactivity. The study also identified GABAergic dysfunction as a major contributor to sensory hyper-reactivity in ASD, emphasizing the importance of early interventions to prevent disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Lang Huang, Jing Wang, Guanmei Liang, Yue Gao, Shi-Yang Jin, Jian Hu, Xiaoxue Yang, Jianpei Lao, Jinfa Chen, Zhou-Cai Luo, Cuixia Fan, Li Xiong, Xinhong Zhu, Tian -Ming Gao, Mei Zhong, Xinping Yang
Summary: Research on Htr3a knockout mice revealed autistic-like behaviors, impaired memory, and reduced susceptibility to seizures. The upregulation of NMDAR in PV+ interneurons plays a critical role in regulating GABAergic input and may be involved in the pathogenesis of autism associated with HTR3A deficiency. The NMDAR system could be a potential therapeutic target for autism.
Article
Biochemistry & Molecular Biology
Ana Lambertos, Maria Angeles Nunez-Sanchez, Carlos Lopez-Garcia, Andres Joaquin Lopez-Contreras, Bruno Ramos-Molina, Rafael Penafiel
Summary: This study explored the expression pattern and function of AZIN2 in the brain. It was found that AZIN2 is mainly expressed in the cerebellum and plays a role in motor function through its regulation of putrescine levels.
Article
Biochemistry & Molecular Biology
Young-Soo Bae, Sang Ho Yoon, Young Sook Kim, Sung Pyo Oh, Woo Seok Song, Jin Hee Cha, Myoung-Hwan Kim
Summary: Treatment for inherited neurodevelopmental disorders often involves repairing neural circuitry rather than addressing the root metabolic cause, offering potential therapeutic approaches. Research has found that metabolic dysfunction leads to excessive NMDAR activity, and restoring synaptic function may ameliorate neurodevelopmental and cognitive deficits.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Madoka Iizumi, Akiko Oota-Ishigaki, Mariko Yamashita, Takashi Hayashi
Summary: The study focuses on the pharmacological effects of anticonvulsants targeting voltage-gated ion channels on GluA1C811S mice, which exhibit increased excitability in response to seizure-inducing stimulation. Results show that anticonvulsive effects are reduced for both GABAergic synapses-targeting anticonvulsants and sodium/calcium channel-blocking anticonvulsants in these mutant mice. This suggests that the AMPA receptor palmitoylation site could be a potential target for developing novel anticonvulsants, with GluA1C811S mice serving as a suitable model for evaluating the efficacy of antiepileptic drugs.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Enora Moutin, Sophie Sakkaki, Vincent Compan, Nathalie Bouquier, Federica Giona, Julie Areias, Elise Goyet, Anne-Laure Hemonnot-Girard, Vincent Seube, Bastien Glasson, Nathan Benac, Yan Chastagnier, Fabrice Raynaud, Etienne Audinat, Laurent Groc, Tangui Maurice, Carlo Sala, Chiara Verpelli, Julie Perroy
Summary: Mutations in the Shank3 gene lead to autism spectrum disorders through disrupting the integrity of the glutamate receptosome, affecting synaptic plasticity and behaviors. Fine-tuning protein-protein interactions within the glutamate receptosome controlled by changes in neuronal activity play a crucial role in regulating plasticity. Restoring the integrity of the glutamate receptosome and its sensitivity to neuronal activity could rescue synaptic transmission, plasticity, and behaviors associated with Shank3 mutations.
MOLECULAR PSYCHIATRY
(2021)
Article
Geriatrics & Gerontology
Jiawei Zhang, Yaxuan Zhang, Yuan Yuan, Lan Liu, Yuwu Zhao, Xiuzhe Wang
Summary: Recent studies indicate a potential relationship between gut microbiota and diabetes-related cognitive dysfunction. This research aimed to explore the longitudinal changes of gut microbiota and cognition in diabetic mice and their wild-type littermates. The findings suggest that abnormal gut microbiota may contribute to cognitive impairment during aging in diabetic mice, possibly through the regulation of neuroinflammation.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Yue Zhang, Ji-Tao Li, Han Wang, Wei-Pan Niu, Chen-Chen Zhang, Yanan Zhang, Xiao-Dong Wang, Tian-Mei Si, Yun-Ai Su
Summary: The study highlights the essential role of TAAR1 in mediating cognitive impairments induced by chronic stress, suggesting that TAAR1 agonists may be uniquely useful for treating MDD-related cognitive impairments.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Alessandra Lintas, Raudel Sanchez-Campusano, Alessandro E. P. Villa, Agnes Gruart, Jose M. Delgado-Garcia
Summary: The study reveals that PV-deficient mice exhibit significant deficits in learning tasks and show changes in spectral power in nuclei involved in reward circuits, indicating impairment in signaling necessary for instrumental learning and natural reward recognition.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Foteini Vasilopoulou, Aina Bellver-Sanchis, Julia Companys-Alemany, Julia Jarne-Ferrer, Alba Irisarri, Veronica Palomera-Avalos, Celia Gonzalez-Castillo, Daniel Ortuno-Sahagun, Coral Sanfeliu, Merce Pallas, Christian Grinan-Ferre
Summary: This study investigates the molecular mechanisms underlying the behavioural and psychological symptoms of dementia (BPSD) in Alzheimer's Disease (AD) patients. It suggests that epigenetic modulation, particularly through G9a methyltransferase and its histone mark (H3K9me2), plays a key role in shaping learning and memory. The study also reveals the association between increased levels of G9a, autophagic deficits, and alterations in synaptic plasticity, providing further understanding of the cognitive decline and BPSD exhibited by the AD model.
Article
Cell Biology
Teodora Oltean, Lorena Itati Ibanez, Tatyana Divert, Tine Ysenbaert, Hannelore Van Eeckhoutte, Vera Goossens, Michael Schotsaert, Ken Bracke, Bert Schepens, Jonathan Maelfait, Nozomi Takahashi, Xavier Saelens, Peter Vandenabeele
Summary: RIPK3 partially protects against disease caused by influenza A virus infection in mice. Active vaccination with M2e viral antigen provides protection against IAV, but this protection is lost in Ripk3(-/-) mice.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Jianfeng Dong, Wen Chen, Nana Liu, Shujuan Chang, Wei Zhu, Jiuhong Kang
Summary: This study found that mice with fetal growth restriction (FGR) displayed symptoms of schizophrenia, such as hyperactivity, social dysfunction, cognitive decline, and impaired sensory motor gating. The upregulation of NRG1 gene in the medial prefrontal cortex (mPFC) of FGR mice was found to be associated with the reduced number of PV interneurons. Reducing NRG1 levels improved schizophrenia behaviors in FGR mice.
CELL DEATH DISCOVERY
(2022)
Article
Cell Biology
Fabian Baalmann, Jana Brendler, Anne Butthof, Yulia Popkova, Kathrin M. Engel, Jurgen Schiller, Karsten Winter, Vera Lede, Albert Ricken, Torsten Schoeneberg, Angela Schulz
Summary: The UDP-glucose receptor P2RY14 is abundantly expressed in A-intercalated cells, collecting duct principal cells, and cells lining the renal papilla, and its function contributes to kidney morphology. The study also reveals the involvement of P2RY14 in the regulation of gene expression related to extracellular matrix proteins and sphingolipid metabolism. Additionally, P2RY14 may play a role in nephroprotection through the regulation of decorin.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Hyosang Kim, Doyoun Kim, Yisul Cho, Kyungdeok Kim, Junyeop Daniel Roh, Yangsik Kim, Esther Yang, Seong Soon Kim, Sunjoo Ahn, Hyun Kim, Hyojin Kang, Yongchul Bae, Eunjoon Kim
Summary: Early postnatal serotonin modulation can prevent adult stage deficits in Arid1b-deficient mice through synaptic transcriptional reprogramming.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Lin Luo, Mateusz C. Ambrozkiewicz, Fritz Benseler, Cui Chen, Emilie Dumontier, Susanne Falkner, Elisabetta Furlanis, Andrea M. Gomez, Naosuke Hoshina, Wei-Hsiang Huang, Mary Anne Hutchison, Yu Itoh-Maruoka, Laura A. Lavery, Wei Li, Tomohiko Maruo, Junko Motohashi, Emily Ling-Lin Pai, Kenneth A. Pelkey, Ariane Pereira, Thomas Philips, Jennifer L. Sinclair, Jeff A. Stogsdill, Lisa Traunmueller, Jiexin Wang, Joke Wortel, Wenjia You, Nashat Abumaria, Kevin T. Beier, Nils Brose, Harold A. Burgess, Constance L. Cepko, Jean-Francois Cloutier, Cagla Eroglu, Sandra Goebbels, Pascal S. Kaeser, Jeremy N. Kay, Wei Lu, Liqun Luo, Kenji Mandai, Chris J. McBain, Klaus-Armin Nave, Marco A. M. Prado, Vania F. Prado, Jeffrey Rothstein, John L. R. Rubenstein, Gesine Saher, Kenji Sakimura, Joshua R. Sanes, Peter Scheiffele, Yoshimi Takai, Hisashi Umemori, Matthijs Verhage, Michisuke Yuzaki, Huda Yahya Zoghbi, Hiroshi Kawabe, Ann Marie Craig
Article
Biochemistry & Molecular Biology
Shunsuke Hoshino, Masaki Kobayashi, Ryoma Tagawa, Ryutaro Konno, Takuro Abe, Kazuhiro Furuya, Kumi Miura, Hiroki Wakasawa, Naoyuki Okita, Yuka Sudo, Yuhei Mizunoe, Yoshimi Nakagawa, Takeshi Nakamura, Hiroshi Kawabe, Yoshikazu Higami
Article
Biochemistry & Molecular Biology
Mateusz C. Ambrozkiewicz, Ekaterina Borisova, Manuela Schwark, Silvia Ripamonti, Theres Schaub, Alina Smorodchenko, A. Ioana Weber, Hong Jun Rhee, Bekir Altas, Ruestem Yilmaz, Susanne Mueller, Lars Piepkorn, Stephen T. Horan, Rachel Straussberg, Sami Zaqout, Olaf Jahn, Ekrem Dere, Marta Rosario, Philipp Boehm-Sturm, Guntram Borck, Katrin Willig, JeongSeop Rhee, Victor Tarabykin, Hiroshi Kawabe
Summary: Kaufman oculocerebrofacial syndrome (KOS) is a severe autosomal recessive disorder caused by biallelic mutations of UBE3B gene. Studies show that Ube3b regulates dendritic branching and spine density autonomously, with knockout leading to altered synaptic physiology and behavior in mice models. This work provides insights into the molecular pathologies underlying intellectual disability-like phenotypes.
MOLECULAR PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Julia Duerr, Dominik H. W. Leitz, Magdalena Szczygiel, Dmytro Dvornikov, Simon G. Fraumann, Clemens Kreutz, Piotr K. Zadora, Ayca Seyhan Agircan, Philip Konietzke, Theresa A. Engelmann, Jan Hegermann, Surafel Mulugeta, Hiroshi Kawabe, Lars Knudsen, Matthias Ochs, Daniela Rotin, Thomas Muley, Michael Kreuter, Felix J. F. Herth, Mark O. Wielpuetz, Michael F. Beers, Ursula Klingmueller, Marcus A. Mall
NATURE COMMUNICATIONS
(2020)
Article
Cell Biology
Xiaoyun Ding, Juyeon Jo, Chih-Yen Wang, Carlo D. Cristobal, Zhongyuan Zuo, Qi Ye, Marvin Wirianto, Aaron Lindeke-Myers, Jong Min Choi, Carrie A. Mohila, Hiroshi Kawabe, Sung Yun Jung, Hugo J. Bellen, Seung-Hee Yoo, Hyun Kyoung Lee
GENES & DEVELOPMENT
(2020)
Article
Neurosciences
Nargis Akter, Ryota Fukaya, Ryota Adachi, Hiroshi Kawabe, Hiroshi Kuba
JOURNAL OF NEUROSCIENCE
(2020)
Article
Neurosciences
Hiroshi Kawabe, Judith Stegmueller
Summary: Ubiquitination is crucial for the regulation of synaptogenesis and synaptic transmission, with abnormalities in E3 genes leading to neurodegenerative disorders and impairing synapse function.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Dominik H. W. Leitz, Julia Duerr, Surafel Mulugeta, Ayca Seyhan Agircan, Stefan Zimmermann, Hiroshi Kawabe, Alexander H. Dalpke, Michael F. Beers, Marcus A. Mall
Summary: Congenital deletion of Nedd4-2 in lung epithelial cells in neonatal mice leads to rapidly progressive lung disease with key features resembling interstitial lung diseases in children (chILD), including hypoxemia, growth failure, sterile pneumonitis, fibrotic lung remodeling, and high mortality. Increased expression of Muc5b and mucus plugging of distal airways, increased ENaC activity and proSP-C mistrafficking are observed in this model, suggesting its potential for studying pathogenesis and preclinical development of therapies for chILD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Noriko Koganezawa, Kenji Hanamura, Manuela Schwark, Dilja Krueger-Burg, Hiroshi Kawabe
Summary: The study used 3D-STED microscopy to analyze the morphology of synapses and found an increase in excitatory synapses in specific regions in a mouse model of autism spectrum disorder. This analysis method will open up new areas in developmental neuroscience in the future.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Dermatology
Shen Yan, Raphael Ripamonti, Hiroshi Kawabe, Maya Ben-Yehuda Greenwald, Sabine Werner
Summary: The ubiquitin ligase NEDD4-1 plays crucial roles in various aspects of skin function, including keratinocyte proliferation, differentiation, and wound repair. Lack of NEDD4-1 in keratinocytes leads to impaired migration and proliferation, resulting in delayed re-epithelialization of wounds. This study highlights the importance of NEDD4-1 in skin homeostasis and identifies its involvement in mitogenic and motogenic signaling pathways.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Iman Lohraseb, Peter McCarthy, Genevieve Secker, Ceilidh Marchant, Jianmin Wu, Naveid Ali, Sharad Kumar, Roger J. Daly, Natasha L. Harvey, Hiroshi Kawabe, Oded Kleifeld, Sophie Wiszniak, Quenten Schwarz
Summary: This study uncovers the important role of NEDD4-mediated ubiquitination in neural crest cell development, regulating the ubiquitination and turnover of Profilin 1 to modulate actin polymerization.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Shreya H. Dhume, Steven A. Connor, Fergil Mills, Parisa Karimi Tari, Sarah H. M. Au-Yeung, Benjamin Karimi, Shinichiro Oku, Reiko T. Roppongi, Hiroshi Kawabe, Shernaz X. Bamji, Yu Tian Wang, Nils Brose, Michael F. Jackson, Ann Marie Craig, Tabrez J. Siddiqui, Katalin Toth
Summary: LRRTM1 and LRRTM2 regulate the density and morphological integrity of excitatory synapses in hippocampal circuits, and play a role in long-term potentiation and enduring fear memory, contributing to fine-tuning of hippocampal circuit connectivity and plasticity.
Article
Neurosciences
Saki Katsube, Noriko Koganezawa, Kenji Hanamura, Katherine J. Cuthill, Victor Tarabykin, Mateusz C. Ambrozkiewicz, Hiroshi Kawabe
Summary: This study reveals that the Ube3b gene acts as a negative regulator of excitatory synapse density in the brain, and its loss leads to a decrease in synaptic density.
NEUROSCIENCE LETTERS
(2023)
Article
Cell Biology
Mai Yamamura, Kenji Hanamura, Noriko Koganezawa, Senami Furubayashi, Tomoaki Shirao, Hiroshi Kawabe
Summary: Methotrexate (MTX) is a commonly used drug for the treatment of acute lymphocytic leukemia or non-Hodgkin lymphoma. However, it can cause neurological side effects such as seizures and cognitive dysfunctions in some patients. The mechanisms behind these side effects, especially on developing neurons, are not well understood.
Review
Cell Biology
Mateusz C. Ambrozkiewicz, Katherine J. Cuthill, Dermot Harnett, Hiroshi Kawabe, Victor Tarabykin
