Article
Cell Biology
Thomas Andreska, Patrick Luningschror, Daniel Wolf, Rhonda L. McFleder, Maurilyn Ayon-Olivas, Marta Rattka, Christine Drechsler, Veronika Perschin, Robert Blum, Sarah Aufmkolk, Noelia Granado, Rosario Moratalla, Markus Sauer, Camelia Monoranu, Jens Volkmann, Chi Wang Ip, Christian Stigloher, Michael Sendtner
Summary: Parkinson's disease (PD) is characterized by impaired motor control. Cortico-striatal synapses, along with brain-derived neurotrophic factor (BDNF) and TrkB, play crucial roles in motor learning. Dopamine depletion in PD reduces the responsiveness of striatal medium spiny projection neurons (SPNs) to BDNF, leading to impaired TrkB processing and disturbed motor function. Sortilin related VPS10 domain containing receptor 2 (SORCS-2) may protect intracellular TrkB clusters from lysosomal degradation.
Article
Cell Biology
Viktor Yarotskyy, Arianna R. S. Lark, Sara R. Nass, Yun K. Hahn, Michael G. Marone, A. Rory McQuiston, Pamela E. Knapp, Kurt F. Hauser
Summary: This study reveals the presence of ClC-1 chloride channels in striatal neurons, mainly localized to the somata of the neurons. These channels modulate neuronal excitability.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Geriatrics & Gerontology
Xi Chen, Zhaofei Yang, Yaping Shao, Kunhyok Kim, Yuanyuan Wang, Ying Wang, Haifeng Wu, Xiaolan Xu, Weidong Le
Summary: The PD mouse model exhibited early changes in neurotransmitters, morphology, and DNA methylation within MSNs, which in turn may contribute to alterations in metabolism, morphology, and epigenetics within the striatum in the later stages of the disease.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Neurosciences
Manli Zhong, Yuhan Wang, Geng Lin, Francesca-Fang Liao, Fu-Ming Zhou
Summary: This study found that in mice, the medium spiny neurons responsible for motor control and cognition in the striatum are not affected by dopamine loss, contrary to previous theories.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Cell Biology
Shannon L. Gourley, Kolluru D. Srikanth, Ellen P. Woon, Hava Gil-Henn
Summary: The study found that Pyk2 stabilizes the structure of the striatal medium spiny neurons, likely providing substrates for inputs, and supports the capacity of mice to arbitrate between novel and familiar behaviors through interactions with the medial prefrontal cortex. Experiments demonstrated that Pyk2 loss caused dendrite arbor and spine loss, while overexpression of Pyk2 or the closely related focal adhesion kinase (FAK) enhanced the ability of mice to arbitrate between rewarded and non-rewarded behaviors. Additionally, combinatorial viral vector strategies suggested that flexible, Pyk2-dependent action involves inputs from the medial prefrontal cortex (mPFC), not the ventrolateral orbitofrontal cortex (OFC).
Article
Multidisciplinary Sciences
Xiaohui Bai, Kun Zhang, Chaopeng Ou, Yanyu Mu, Dongmei Chi, Jianxing Zhang, Jingxiu Huang, Xile Li, Yingjun Zhang, Wan Huang, Handong Ouyang
Summary: This study found that the expression of AKAP150 in the NAc is upregulated during morphine withdrawal, and inhibiting AKAP150 has a positive effect on alleviating withdrawal symptoms and improving test performance. AKAP150 in NAc D1R-MSNs is related to the performance of morphine withdrawal tests, while AKAP150 in NAc D2R-MSNs is relevant to the severity of physical responses.
Article
Biochemistry & Molecular Biology
Anna Kutschenko, Selma Staege, Karen Grutz, Hannes Glab, Norman Kalmbach, Thomas Gschwendtberger, Lisa M. Henkel, Johanne Heine, Anne Grunewald, Andreas Hermann, Philip Seibler, Florian Wegner
Summary: Myoclonus-dystonia (DYT-SGCE), a rare neurological disorder caused by mutations in the SGCE gene, is characterized by abnormal Ca2+ signaling, synaptic density, and electrical properties in patient-derived neurons. This study provides insights into the pathophysiology of the disease and potential novel therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Ettel Keifman, Camila Coll, Cecilia Tubert, Rodrigo M. Paz, Juan E. Belforte, Mario G. Murer, Barbara Y. Braz
Summary: In Parkinson's disease patients and rodent models, loss of dopaminergic neurons results in severe motor disabilities. However, in rodents, general motility is preserved after early postnatal loss of dopaminergic neurons. This preservation is likely due to functional changes in certain neurons in the brain.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Neurosciences
Guendalina Bergonzoni, Jessica Doring, Marta Biagioli
Summary: Huntington's disease is a devastating neurodegenerative disorder caused by an aberrant expansion of the CAG tract within the HTT gene. Despite the ubiquity of the HTT gene, striatal Medium-sized Spiny Neurons are particularly vulnerable to the HD mutation, with D1R and D2R displaying different susceptibility. Understanding cell type-specific gene expression dysregulation in the striatum may offer new paths for therapeutic intervention in HD patients.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Cell Biology
Weston Fleming, Junuk Lee, Brandy A. Briones, Scott S. Bolkan, Ilana B. Witten
Summary: The study revealed that high endogenous acetylcholine event frequency is correlated with greater extinction of cocaine-context associations in male mice, and extinction is related to a weakening of glutamatergic synapses across different MSN subtypes. Manipulating ChIN activity bidirectionally influences the rate of extinction and associated plasticity at MSNs.
Article
Neurosciences
Aaron J. Barbour, Sara R. Nass, Yun K. Hahn, Kurt F. Hauser, Pamela E. Knapp
Summary: People infected with HIV are susceptible to damage in the striatum and hippocampus, leading to motor and memory impairments. GABAergic dysfunction from HIV infection and viral proteins like Tat have been well-documented, and loss of KCC2 may disrupt GABA(A)R-mediated hyperpolarization and inhibition. Targeting KCC2 activity could be a therapeutic approach to alleviate motor disturbances related to HIV.
Article
Pharmacology & Pharmacy
Elia Mota, Segolene Bompierre, Dahdjim Betolngar, Liliana R. Castro, Pierre Vincent
Summary: This study reveals the functional contribution of PDE2A, PDE4, and PDE10A in regulating cAMP/PKA response to dopamine stimulation in the striatum. PDE10A is found to play a key role in reducing cAMP levels back to baseline and dephosphorylating PKA substrates. Inhibiting PDE10A dampens responsiveness to dopamine, while inhibiting PDE2A or PDE4 strengthens dopamine action.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Neurosciences
Hiroaki Oizumi, Ryota Imai, Toru Suzuki, Yuji Omiya, Kenji F. Tanaka, Masaru Mimura, Kazushige Mizoguchi
Summary: Recent studies have indicated that the traditional Japanese Kampo medicine ninjin'yoeito (NYT) may be a novel therapeutic option for impaired motivation in humans and animals. This study analyzed the effect of NYT on motivated behaviors in mice with neurodegeneration-related apathy, finding that NYT did not suppress effort-based operant responding but did prevent anhedonic behavior, suggesting its beneficial effect on motivation is mediated through specific neuromodulatory pathways.
Article
Multidisciplinary Sciences
Kim Le Cann, Alec Foerster, Corinna Roesseler, Andelain Erickson, Petra Hautvast, Sebastian Giesselmann, Daniel Pensold, Ingo Kurth, Markus Rothermel, Virginia B. Mattis, Geraldine Zimmer-Bensch, Stephan von Hoersten, Bernd Denecke, Tim Clarner, Jannis Meents, Angelika Lampert
Summary: Huntington's disease (HD) is a neurodegenerative disorder caused by a genetic mutation, affecting specific neuronal populations in the brain. Differentiating hiPS cells into striatal neurons to model HD faces challenges in replicating previous protocols due to heterogeneity in neuronal populations and variability in Nav channels. The study highlights difficulties in generating accurate hiPS cell-derived MSNs for studying HD in vitro.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Yafang Zhang, Jennifer Ben Nathan, Amanda Moreno, Riley Merkel, Michelle W. Kahng, Matthew R. Hayes, Benjamin C. Reiner, Richard C. Crist, Heath D. Schmidt
Summary: The high rates of relapse associated with current medications used to treat opioid use disorder (OUD) necessitate research that expands our understanding of the neural mechanisms regulating opioid taking to identify molecular substrates that could be targeted by novel pharmacotherapies to treat OUD. Recent studies show that activation of calcitonin receptors (CTRs) is sufficient to reduce the rewarding effects of addictive drugs in rodents. Central CTR signaling was investigated in the context of opioid-mediated behaviors using single nuclei RNA sequencing (snRNA-seq), fluorescent in situ hybridization (FISH), and immunohistochemistry (IHC) techniques. CTR expression was found in specific cell types in the nucleus accumbens (NAc), with interesting disparities between D1R- and D2R-expressing medium spiny neurons (MSNs). Functional significance was revealed through knockdown experiments, with reduced CTR expression in D1R- versus D2R-expressing MSNs potentiating/augmenting opioid self-administration and attenuating it, respectively.
NEUROPSYCHOPHARMACOLOGY
(2023)
Review
Clinical Neurology
Daisuke Ito, Satoru Morimoto, Shinichi Takahashi, Kensuke Okada, Jin Nakahara, Hideyuki Okano
Summary: Significant progress has been made in drug screening for amyotrophic lateral sclerosis using patient-derived induced pluripotent stem cells, leading to the identification of candidate drugs and the advancement of clinical trials. This stem cell-based approach shows safety and positive effects, reducing costs and time compared to animal testing.
Article
Neurosciences
Mitsuhiro Oishi, Stefan Passlick, Yoshihiko Yamazaki, Miyuki Unekawa, Ruka Adachi, Mayumi Yamada, Itaru Imayoshi, Yoshifumi Abe, Christian Steinhaeuser, Kenji F. Tanaka
Summary: Nerve/glial antigen 2 (NG2) is a protein marker that can be used to target specific cell types in transgenic mice. By combining different gene induction systems, researchers have developed a method to selectively control the function of mural cells and NG2 glia. This research provides valuable tools and methods for studying the function and mechanisms of these cells.
Article
Biotechnology & Applied Microbiology
Ryota Tamura, Hiroyuki Miyoshi, Kent Imaizumi, Masahiro Yo, Yoshitaka Kase, Tsukika Sato, Mizuto Sato, Yukina Morimoto, Oltea Sampetrean, Jun Kohyama, Munehisa Shinozaki, Atsushi Miyawaki, Kazunari Yoshida, Hideyuki Saya, Hideyuki Okano, Masahiro Toda
Summary: This study demonstrates the potential benefit of gene-edited induced pluripotent stem cells (iPSCs) for the treatment of invasive glioma stem cells (GSCs). Neural stem cells (NSCs) derived from CRISPR/Cas9-edited iPSCs expressing a suicide gene showed enhanced tumor-trophic migratory capacity and significant in vivo antitumor effects. The study also identified key signaling pathways and gene expressions associated with the efficacy of therapeutic iPSC-NSCs.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Satoru Morimoto, Koichi Saeki, Masaru Takeshita, Kunio Hirano, Mariko Shirakawa, Yumiko Yamada, Shiho Nakamura, Fumiko Ozawa, Hideyuki Okano
Summary: The study developed an intranasal vaccine for COVID-19 by using a Sendai virus vector loaded with the receptor binding domain of SARS-CoV-2 as an antigen. The vaccine induced a strong immune response, with increased levels of S-RBD-specific antibodies in serum and bronchoalveolar lavage fluid. The booster dose further enhanced the production of neutralizing antibodies, indicating the effectiveness of the vaccine.
Article
Cell Biology
Sho Yoshimatsu, Mayutaka Nakajima, Iki Sonn, Rie Natsume, Kenji Sakimura, Ena Nakatsukasa, Toshikuni Sasaoka, Mari Nakamura, Takashi Serizawa, Tsukika Sato, Erika Sasaki, Hongkui Deng, Hideyuki Okano
Summary: This study compared the gene expression profiles of mouse, human, and common marmoset EPSCs using transcriptomic approaches. The marmoset EPSC-like cells displayed a distinct morphology but exhibited a pluripotent state similar to embryonic stem cells. They also showed interspecies chimeric contribution to mouse embryos. Furthermore, the gene expression of the marmoset EPSC-like cells resembled that of human EPSCs. Overall, this study evaluated the efficacy of the method for deriving marmoset EPSCs.
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
Biochemistry & Molecular Biology
Tosho Kondo, Ihori Ebinuma, Hirotaka Tanaka, Yukitoshi Nishikawa, Takaki Komiya, Mitsuru Ishikawa, Hideyuki Okano
Summary: In this study, an effective high-throughput screening system was established using induced pluripotent stem cells (iPSCs) to generate motor neurons. The generated motor neurons exhibited characteristics similar to ALS neurons and showed abnormal protein accumulation and hyperexcitability. Treatment with rapamycin and retigabine normalized activity and improved neuronal survival. This study provides a valuable platform for discovering novel ALS therapeutics and personalized medicine approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Juri Murata, Miyuki Unekawa, Yuya Kudo, Maho Kotani, Iwao Kanno, Yoshikane Izawa, Yutaka Tomita, Kenji F. Tanaka, Jin Nakahara, Kazuto Masamoto
Summary: This study found that cerebral microvascular obstruction is related to recurrent stroke and decreased cerebral blood flow with age. The study showed a relationship between capillary lumen space and embolism formation. Constriction of capillaries increases the risk of developing microcirculation embolism.
Article
Biochemistry & Molecular Biology
Hitomi Ono-Minagi, Tsutomu Nohno, Takashi Serizawa, Yu Usami, Takayoshi Sakai, Hideyuki Okano, Hideyo Ohuchi
Summary: This study investigates the embryonic origin of salivary and lacrimal glands using transgenic mice and demonstrates that these glands contain cells derived from all three germ layers. Specifically, a subset of cells derived from neural crest differentiate into epithelial cells and express high levels of stem cell markers. These cells play an important role in the regenerative response following tissue damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Hiroya Kobayashi, Koji Ueda, Satoru Morimoto, Mitsuru Ishikawa, Nicolas Leventoux, Ryogen Sasaki, Yoshifumi Hirokawa, Yasumasa Kokubo, Hideyuki Okano
Summary: The proteins in extracellular vesicles derived from astrocytes in patients with Kii ALS/PDC exhibit distinctive patterns compared to healthy individuals, with increased proteins related to proteostasis and decreased proteins related to anti-inflammation.
NEUROLOGICAL SCIENCES
(2023)
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.
Review
Medicine, General & Internal
Takahiro Shibata, Syoichi Tashiro, Masaya Nakamura, Hideyuki Okano, Narihito Nagoshi
Summary: Cell transplantation therapy using human-induced pluripotent stem cell-derived neural stem/progenitor cells has shown efficacy in treating the subacute phase of spinal cord injury. However, there is a lack of focus on treatment in the chronic phase, which poses challenges in overcoming factors specific to chronic SCI. Combining different therapies and addressing issues in severe injury models and functional recovery are important for regenerative therapy in chronic SCI.
MEDICINA-LITHUANIA
(2023)
Article
Geriatrics & Gerontology
Shohei Komaki, Masatoshi Nagata, Eri Arai, Ryo Otomo, Kanako Ono, Yukiko Abe, Hideki Ohmomo, So Umekage, Natsuko Shinozaki, Tsuyoshi Hachiya, Yoichi Sutoh, Yayoi Otsuka-Yamasaki, Yasumichi Arai, Nobuyoshi Hirose, Akio Yoneyama, Hideyuki Okano, Makoto Sasaki, Yae Kanai, Atsushi Shimizu
Summary: This study explored the epigenetic signatures of exceptional healthy longevity and found that it depends not only on maintaining young epigenetic states but also on advanced states of specific epigenetic regions.
LANCET HEALTHY LONGEVITY
(2023)
Review
Biochemistry & Molecular Biology
Hideyuki Okano, Satoru Morimoto, Chris Kato, Jin Nakahara, Shinichi Takahashi
Summary: In recent years, clinical trials using iPSC technology for disease modeling and drug discovery have shown promising results, particularly for the treatment of ALS. ROPi has been identified as a potential ALS treatment and has undergone clinical trials and reverse translational research, demonstrating its ability to delay disease progression and prolong survival in ALS patients.
JOURNAL OF NEUROCHEMISTRY
(2023)