Article
Endocrinology & Metabolism
Jared S. Farrar, Joseph C. Lownik, Grayson W. Way, Matthew C. Rodriguez, Francesco S. Celi, Rebecca K. Martin
Summary: The Adipoq-Cre transgenic mouse is commonly used in obesity and type 2 diabetes research, with a strong genetic linkage to the Adipoq-Cre transgene. The genomic insertion site was identified within the Tbx18 gene locus on chromosome 9, causing a significant decrease in Tbx18 gene expression in adipose tissue. Additional genes Kng2, Kng1, Eif4a2, and Rfc4 were also inserted in the Adipoq-Cre transgenic mouse, potentially impacting various tissues.
Article
Biochemical Research Methods
Christopher Brian Currin, Joseph Valentino Raimondo
Summary: This study investigates the effect of dendritically targeted inhibition on dendritic excitability using computational models. The inhibitory effectiveness of dendritic GABAergic synapses accumulates at encircled branch junctions, dependent on the number and location of synapses. This finding helps determine the most inhibitory distribution of GABAergic synapses.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Neda A. M. Nafchi, Ellie M. M. Chilcott, Sharon Brown, Heidi R. R. Fuller, Melissa Bowerman, Rafael J. J. Yanez-Munoz
Summary: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in the survival motor neuron (SMN) 1 gene. A novel codon-optimized hSMN1 transgene was developed and lentiviral vectors with different promoters were tested for optimal expression. The integration-deficient lentiviral vectors showed high expression of the optimized transgene and are considered safer. Neonatal delivery of the optimized transgene using adeno-associated viral vectors resulted in a significant increase in SMN protein levels in SMA mouse models.
Article
Clinical Neurology
Hyowon Hong, Sae-Bom Yoon, Jung Eun Park, Jung In Lee, Hyun Young Kim, Hye Jin Nam, Heeyeong Cho
Summary: This study established an RTT brain organoid model and investigated the impact of MeCP2 dysfunction on neural development and gliogenesis. It was found that MeCP2 modulates the expansion of neural progenitor cells by regulating the BMP pathway. These findings contribute to a better understanding of the pathogenesis of RTT.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Neurosciences
Czarina Ramos, Stefano Lutzu, Miwako Yamasaki, Yuchio Yanagawa, Kenji Sakimura, Susumu Tomita, Masahiko Watanabe, Pablo E. Castillo
Summary: This study provides the first direct evidence of functional extrasynaptic kainate receptors (KARs) on mossy cells (MCs) in the hippocampus. These KARs are mainly located extrasynaptically and play a critical role in the activity of MCs. Increases in ambient glutamate can activate the KARs on MCs.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Cell & Tissue Engineering
Yuka Kasahara, Daiki Masukawa, Kenta Kobayashi, Miwako Yamasaki, Masahiko Watanabe, Yoshio Goshima
Summary: Neurogenesis in the hippocampus is regulated by L-DOPA and its receptor GPR143 independently of dopamine. Low concentrations of L-DOPA promote neurogenesis, and its effect is abolished in GPR143 gene-deficient mice. Decreased neurogenesis and exacerbated depression-like behavior are observed in adult GPR143 gene-deficient mice, but can be attenuated by replenishment of GPR143 in the hippocampus.
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
Neurosciences
Mayuko Hashimoto, Masaki Fujimoto, Kohtarou Konno, Ming-Liang Lee, Yui Yamada, Koya Yamashita, Chitoku Toda, Michio Tomura, Masahiko Watanabe, Osamu Inanami, Hiroshi Kitamura
Summary: This study reveals that hypothalamic USP2 regulates blood glucose levels through the ROS-AMPK-sympathetic nerve axis. Inhibition of USP2 leads to mitochondrial dysfunction and AMPK phosphorylation, resulting in increased blood glucose and norepinephrine levels.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Eriko Miura, Masahiko Watanabe
Summary: This study investigated the expression of calcineurin (CN) in the mouse brain and found that CNA alpha, CNA, and CNB1 were predominantly expressed. The protein localization experiments revealed that CNB1 and CNA were co-distributed in various cerebellar neurons and glia, while CNA alpha was exclusive to granule cell elements. These findings provide anatomical evidence for the regulatory roles of CN in long-term depression and transmitter release function at synapses.
NEUROSCIENCE RESEARCH
(2022)
Article
Cell Biology
Takeshi Uemura, Emi Suzuki-Kouyama, Shiori Kawase, Taiga Kurihara, Misato Yasumura, Tomoyuki Yoshida, Shuya Fukai, Maya Yamazaki, Peng Fei, Manabu Abe, Masahiko Watanabe, Kenji Sakimura, Masayoshi Mishina, Katsuhiko Tabuchi
Summary: This study found that the presynaptic cell adhesion molecules NRXNs play a crucial role in the survival of cerebellar granule cells and synapse formation. They not only maintain cell survival, but also promote the formation of presynaptic protein clusters and the secretion of neurotrophic factors.
Article
Neurosciences
Keita Mori, Michinori Koebis, Kazuki Nakao, Shizuka Kobayashi, Yuji Kiyama, Masahiko Watanabe, Toshiya Manabe, Yuichi Iino, Atsu Aiba
Summary: This study investigates the function of Calsyntenins (CLSTNs) by generating triple knockout (TKO) mice lacking all CLSTN paralogs. The mutant mice exhibited freezing behavior in novel environments and hypersensitivity to stress. Glucose levels under stress were significantly higher in the mutant mice than in the wild-type controls. Phenotypes such as decreased motivation, which had not been reported in single Clstn knockout mice, were newly discovered. The TKO mice generated in this study serve as an important mouse model for further understanding the function of CLSTN.
Review
Medicine, General & Internal
Sumiyasu Ishii, Noriyuki Koibuchi
Summary: COUP-TFII is a developmental gene that plays a crucial role in kidney formation and survival during embryonic development, as well as in protecting against acute kidney injury in adults. Ongoing research is investigating the involvement of COUP-TFII in podocyte development and diabetic kidney disease, and the identification of potential ligands suggests it could be a novel therapeutic target for renal diseases in the future.
Article
Neurosciences
Qin Zhao, Tetsufumi Ito, Chika Soko, Yoshie Hori, Takafumi Furuyama, Hiroyuki Hioki, Kohtarou Konno, Miwako Yamasaki, Masahiko Watanabe, Satoshi Ohtsuka, Munenori Ono, Nobuo Kato, Ryo Yamamoto
Summary: This study investigates the histochemical features of DA(DR-PAG) neurons projecting to the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST) in mice. Two subpopulations of these neurons were identified, TH1/VIP- and TH-/VIP1, with the latter being non-DA noncanonical DAT neurons. Both subpopulations innervate the same regions, and the TH-/VIP1 subpopulation was found to be VGlut2-positive neurons.
Article
Rheumatology
Nobuya Abe, Masato Tarumi, Yuichiro Fujieda, Nobuhiko Takahashi, Kohei Karino, Mona Uchida, Michihito Kono, Yuki Tanaka, Rie Hasebe, Masaru Kato, Olga Amengual, Yoshiyuki Arinuma, Kenji Oku, Wakiro Sato, Khin Khin Tha, Miwako Yamasaki, Masahiko Watanabe, Tatsuya Atsumi, Masaaki Murakami
Summary: The study investigates the effects of stress on the pathophysiology of neuropsychiatric lupus (NPSLE) in systemic lupus erythematosus (SLE) using lupus-prone mice and patient data.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Alvin Susetyo, Sumiyasu Ishii, Yuki Fujiwara, Izuki Amano, Noriyuki Koibuchi
Summary: Perinatal hypothyroidism impairs cerebellar development and motor coordination. Treatment with an HDAC3 inhibitor reverses the developmental defects and increases the transcription levels of thyroid hormone-responsive genes in the cerebellum.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Ayane Ninomiya, Izuki Amano, Michifumi Kokubo, Yusuke Takatsuru, Sumiyasu Ishii, Hirokazu Hirai, Nobutake Hosoi, Noriyuki Koibuchi
Summary: This study reveals the effects of congenital hypothyroidism in neurons on adult central nervous system function, with a focus on the cerebellum where a series of abnormalities were found. These findings provide insights into the cellular and molecular mechanisms underlying congenital hypothyroidism-induced dysfunctions of the central nervous system and cerebellum.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Amy Cheung, Kotaro Konno, Yuka Imamura, Aya Matsui, Manabu Abe, Kenji Sakimura, Toshikuni Sasaoka, Takeshi Uemura, Masahiko Watanabe, Kensuke Futai, Nils Brose
Summary: The study reveals the involvement of Nrxn genes in the modulation of 5-HT transmission and behavior, suggesting a potential link between Nrxn mutations and ASD.
Article
Biology
Kieran A. Boyle, Erika Polgar, Maria Gutierrez-Mecinas, Allen C. Dickie, Andrew H. Cooper, Andrew M. Bell, Evelline Jumolea, Adrian Casas-Benito, Masahiko Watanabe, David I. Hughes, Gregory A. Weir, John S. Riddell, Andrew J. Todd
Summary: This study investigates the role of interneurons that continue to express neuropeptide Y (NPY-INs) in the adult mouse spinal cord. The findings suggest that activation of NPY-INs reduces acute pain and pruritogen-evoked itch, while silencing them causes exaggerated itch responses. Silencing another population of inhibitory interneurons also increases itch, but to a lesser extent.
Article
Multidisciplinary Sciences
Kohtarou Konno, Miwako Yamasaki, Taisuke Miyazaki, Masahiko Watanabe
Summary: The gold-standard fixative for immunohistochemistry is 4% formaldehyde; however, it limits antibody access to buried target molecules. To solve this problem, we used glyoxal as a fixative, which greatly improved antibody penetration, uncovering signals for buried molecules. Glyoxal also enhanced immunosignals of most other molecules, including the controversial synaptic adhesion molecule Neuroligin 1.