Article
Neurosciences
Karim S. Ibrahim, Salah El Mestikawy, Khaled S. Abd-Elrahman, Stephen S. G. Ferguson
Summary: Huntington's disease (HD) is a neurodegenerative disease characterized by motor and cognitive impairments. The role of vesicular glutamate transporter-3 (VGLUT3) in HD pathophysiology is unclear. This study found that VGLUT3 deletion rescued motor and cognitive deficits in HD mouse models, likely through the activation of Akt and ERK1/2 pathways. These findings suggest that VGLUT3 could be a potential target for HD therapeutics.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Genetics & Heredity
Karolina Pierzynowska, Magdalena Podlacha, Dorota Luszczek, Estera Rintz, Lidia Gaffke, Zuzanna Szczudlo, Marta Tomczyk, Ryszard T. Smolenski, Grzegorz Wegrzyn
Summary: This study identified abnormal hair morphology as a potential simple marker for testing therapeutic effects or disease progression in widely used HD mouse models R6/1 and R6/2.
Article
Biochemistry & Molecular Biology
Roberto Speziale, Camilla Montesano, Giulia Di Pietro, Daniel Oscar Cicero, Vincenzo Summa, Edith Monteagudo, Laura Orsatti
Summary: Huntington's disease (HD) is a genetic condition caused by the expansion of a specific sequence in the huntingtin gene. There is a lack of effective treatments for HD, highlighting the need for reliable mouse models for preclinical studies. This study utilized a urinary liquid chromatography-high-resolution mass spectrometry analysis to identify metabolic changes in different HD mouse models, aiming to improve our understanding of the disease and identify potential biomarkers.
Article
Neurosciences
Estibaliz Etxeberria-Rekalde, Saioa Alzola-Aldamizetxebarria, Stefanie Flunkert, Isabella Hable, Magdalena Daurer, Joerg Neddens, Birgit Hutter-Paier
Summary: Researchers conducted a comprehensive analysis of R6/2 mice, identifying Ctip2 and TSPO as new markers associated with the motor system and early neuroinflammation, providing a new direction for the study of HD.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Neurosciences
S. M. Holley, K. D. Oikonomou, C. M. Swift, L. Mohan, B. Matthews, O. Vega, G. Mkrtchyan, C. Cepeda, M. S. Levine
Summary: As Huntington's disease progresses, there is a loss of neurons in the striatum and thinning of the cerebral cortex. This study found reduced connectivity between thalamic cells and their targeted cortical regions in a mouse model of HD, suggesting impaired thalamocortical information transmission.
Article
Biochemistry & Molecular Biology
Davide De Biase, Valeria Valente, Andrea Conte, Francesca Cammarota, Nicola Boccella, Lucia D'Esposito, Ilaria D'Aquino, Orlando Paciello, Simona Paladino, Giovanna Maria Pierantoni
Summary: The loss of HIPK2 in Hipk2-KO mice leads to neuronal loss and morphological alterations in the central nervous system, as well as muscle pathologies in the skeletal and cardiac muscles, suggesting its potential relevance for different aspects of human pathology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Marie Katrin Bondulich, Yilan Fan, Yeojin Song, Flaviano Giorgini, Gillian P. Bates
Summary: KMO depletion in HD mice can normalize dysregulated KP genes in peripheral tissues and increase levels of neuroprotective metabolites, but it does not improve behavioral phenotypes. Peripheral inflammation levels, including pro-inflammatory cytokines, are modulated by KMO deletion, suggesting a potential role in HD pathogenesis.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Masayo Hashimoto, Kenichi Watanabe, Kan Miyoshi, Yukako Koyanagi, Jun Tadano, Izuru Miyawaki
Summary: The study in the R6/2 mouse model revealed disturbances in histidine metabolism in brain tissue, as well as differential metabolites related to arginine and cysteine metabolism. Additionally, dysregulation of lipid metabolism was identified, indicating a wide range of metabolic alterations in the brain of R6/2 mice.
Article
Neurosciences
Julien Gasser, Gaelle Gillet, Jorge S. Valadas, Laura Rouviere, Apoorva Kotian, Wenqiang Fan, James Keaney, Irena Kadiu
Summary: This study found that Huntington's disease leads to brain infiltration of peripheral lymphoid and myeloid cells, resulting in activation of microglia and enhanced phagocytic functions, which in turn contribute to synaptic loss. Similar observations were made in human Huntington's disease brains. Overall, targeting microglial functions related to synaptic surveillance and pruning may have therapeutic benefits in attenuating cognitive decline and psychiatric symptoms of Huntington's disease.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Cell Biology
Cong Liu, Xing Gao, Ruo-Xi Shi, Ying-Ying Wang, Xuan-Cheng He, Hong-Zhen Du, Baoyang Hu, Jianwei Jiao, Chang-Mei Liu, Zhao-Qian Teng
Summary: This study aims to elucidate the role and mechanisms of microglial TGM2 in the brain. Deletion of microglial Tgm2 causes impaired synaptic pruning, reduced anxiety, and increased cognitive deficits in mice. At the molecular level, the phagocytic genes are significantly down-regulated in TGM2-deficient microglia. This study reveals a novel role of microglial TGM2 in regulating synaptic remodeling and cognitive function, indicating its essentiality for proper neural development.
CELL PROLIFERATION
(2023)
Article
Neurosciences
H. Wang, N. Del Mar, Y. Deng, A. Reiner
Summary: The study found that the mGluR2/3 agonist LY379268 can improve the motor, neuronal, and neurochemical phenotype in Huntington's disease mice, primarily by increasing BDNF and reducing enkephalinergic neuron loss in the striatum. Daily LY379268 injections also rescued BDNF expression in thalamic parafascicular neurons, which project to the striatum, further protecting enkephalinergic striatal neurons. This suggests that mGluR2/3 agonists may be a potential approach for slowing enkephalinergic neuron loss and disease progression in Huntington's disease.
NEUROSCIENCE LETTERS
(2021)
Article
Cell Biology
Anissa Elahi, Jacen Emerson, Jacob Rudlong, Jeffrey W. Keillor, Garrick Salois, Adam Visca, Peter Girardi, Gail V. W. Johnson, Christoph Proschel
Summary: The study revealed that deletion of TG2 from astrocytes significantly improved motor function in a spinal cord contusion injury (SCI) model, reducing astrocyte markers and SOX9 positive cell numbers. Activation of fatty acid metabolism and energy pathways promotes metabolic coupling between neurons and astrocytes.
Article
Biochemistry & Molecular Biology
Jacen Emerson, Thomas Delgado, Peter Girardi, Gail V. W. Johnson
Summary: Astrocytes are important support cells in the central nervous system that affect the function and recovery of neurons. Reactive astrocytes can have both beneficial and harmful effects on injured neurons, and understanding the factors and pathways that determine their reactive phenotypes is still a developing field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Katerina D. Oikonomou, Elissa J. Donzis, Minh T. N. Bui, Carlos Cepeda, Michael S. Levine
Summary: The study using the R6/2 mouse model found that the amplitude of somatic calcium transients in CPNs of Huntington's disease patients was reduced, but compensated by increased decay times, so that transient areas were similar between genotypes. Ryanodine receptors (RyRs) and L-type calcium channels may be potential targets for therapeutic intervention.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Article
Cell Biology
Akanksha Baharani, Zelan Wei, William J. Roesler, Darrell D. Mousseau
Summary: In this study, the researchers investigated kinase activity patterns and signal cascades in neural tissues of the R6/2 transgenic mouse model of Huntington's disease. They identified changes in several signaling pathways, as well as the involvement of the Rho-Rac GTPase cascade in cytoskeleton organization. The study also revealed higher levels of phosphorylated Ser138-profilin in embryonic R6/2 mouse samples, which decreased progressively during postnatal symptomatic stages.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Article
Behavioral Sciences
Maksym Kopanitsa, Kimmo K. Lehtimaki, Markku Forsman, Ari Suhonen, Juho Koponen, Tuukka O. Piiponniemi, Anna-Mari Karkkainen, Pavlina Pavlidi, Artem Shatillo, Patrick J. Sweeney, Avia Merenlender-Wagner, Joel Kaye, Aric Orbach, Antti Nurmi
Summary: The study revealed that mice treated with cuprizone exhibited multiple cognitive deficits, including slower responses, more errors, and significantly lower levels of contextual freezing. Diffusion tensor imaging showed treatment-dependent changes in white matter areas, indicating developing demyelination and/or axonal damage. The findings suggest that translational touchscreen operant tests and fear conditioning paradigms can reliably detect cognitive consequences of cuprizone treatment.
GENES BRAIN AND BEHAVIOR
(2021)
Article
Public, Environmental & Occupational Health
Kurunthachalam Kannan, Alexa Stathis, Matthew J. Mazzella, Syam S. Andra, Dana Boyd Barr, Stephen S. Hecht, Lori S. Merrill, Aubrey L. Galusha, Patrick J. Parsons
Summary: A consortium of laboratories under CHEAR used a multifaceted quality assurance program to ensure reliable and reproducible data quality for trace organics analyses. Participation in external quality assurance programs and the use of a common quality control pool for each project sample batch improved organic chemical analysis capabilities and accuracy. The laboratories' methods were verified through NIST SRMs, demonstrating acceptable analytical precision and excellent reliability across various batches.
INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH
(2021)
Article
Neurosciences
Xiaofeng Gu, Jeffrey Richman, Peter Langfelder, Nan Wang, Shasha Zhang, Monica Banez-Coronel, Huei-Bin Wang, Lucia Yang, Lalini Ramanathan, Linna Deng, Chang Sin Park, Christopher R. Choi, Jeffrey P. Cantle, Fuying Gao, Michelle Gray, Giovanni Coppola, Gillian P. Bates, Laura P. W. Ranum, Steve Horvath, Christopher S. Colwell, X. William Yang
Summary: In this study, a BAC-CAG mouse model was established to investigate the pathogenesis of Huntington's disease, and it was found that the uninterrupted CAG repeat length is significantly correlated with striatal transcriptionopathy, but not with polyglutamine length. Additionally, somatic CAG repeat instability and nuclear mHTT aggregation are best correlated with early-onset pathology and locomotor and sleep deficits.
Article
Clinical Neurology
Sandra Fienko, Christian Landles, Kirupa Sathasivam, Sean J. McAteer, Rebecca E. Milton, Georgina F. Osborne, Edward J. Smith, Samuel T. Jones, Marie K. Bondulich, Emily C. E. Danby, Jemima Phillips, Bridget A. Taxy, Holly B. Kordasiewicz, Gillian P. Bates
Summary: Fienko et al. show that alternative processing of human huntingtin (HTT) mRNA to generate HTT1a occurs in YAC128 mice, which has implications for the design of huntingtin-lowering therapies.
Article
Multidisciplinary Sciences
Shuzhang Yang, Shin Yamazaki, Kimberly H. Cox, Yi-Lin Huang, Evan W. Miller, Joseph S. Takahashi
Summary: This study reports the discovery of temperature-sensitive ultradian rhythms in mammalian fibroblasts, which are independent of the cell cycle and circadian clock. These ultradian rhythms are synchronized through cellular coupling and metabolic feedback mechanisms, and play a role in balancing energy demands in cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Environmental Sciences
Stefanie A. Busgang, Syam S. Andra, Paul Curtin, Elena Colicino, Matthew J. Mazzella, Moira Bixby, Alison P. Sanders, John D. Meeker, Marissa Hauptman, Shirisha Yelamanchili, Wanda Phipatanakul, Chris Gennings
Summary: Environmental research often relies on urinary biomarkers which require dilution correction to accurately measure exposures. Specific gravity (SG) and creatinine (UCr) are commonly measured urinary dilution factors. Epidemiologic studies may assess only one of these measures, making it difficult to pool studies that may otherwise be able to be combined.
ENVIRONMENTAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Karlijne W. Geijtenbeek, Jolien Janzen, Aleksandra E. Bury, Alicia Sanz-Sanz, Ron A. Hoebe, Marie K. Bondulich, Gillian P. Bates, Eric A. J. Reits, Sabine Schipper-Krom
Summary: Huntington's disease, caused by a gene mutation, may be treated by lowering the levels of mutant protein. Research has shown that in affected brain regions, the proteasome separates from PA28αβ, which may be related to disease progression.
Article
Clinical Neurology
Edward J. Smith, Kirupa Sathasivam, Christian Landles, Georgina F. Osborne, Michael A. Mason, Casandra Gomez-Paredes, Bridget A. Taxy, Rebecca E. Milton, Anne Ast, Franziska Schindler, Chuangchuang Zhang, Wenzhen Duan, Erich E. Wanker, Gillian P. Bates
Summary: Targeting huntingtin expression to lower its levels is crucial for the treatment of Huntington's disease. Researchers have found that the mutant exon 1 huntingtin protein initiates the aggregation process, which can be detected throughout the central nervous system (CNS) in mouse models of the disease within one to two months.
BRAIN COMMUNICATIONS
(2022)
Meeting Abstract
Clinical Neurology
Marie K. Bondulich, Lauren M. Byrne, Arzo Iqbal, Iulia M. Nita, Maria Canibano-Pico, Jemima M. Phillips, Edward Wild, Gillian P. Bates
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Sandra Fienko, Christian Landles, Kirupa Sathasivam, Casandra Gomez-Paredes, Sean McAteer, Rebecca Milton, Georgina F. Osborne, Samuel T. Jones, Jemima M. Phillips, Holly B. Kordasiewicz, Gillian P. Bates
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Christian Landles, Georgina F. Osborne, Rebecca E. Milton, Alexandre Jean, Stuart McLarnon, Chuangchuang Zhang, Wenzhen Duan, Gillian P. Bates
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Aikaterini-Smaragdi Papadopulou, Christian Landles, Edward Smith, Marie Bondulich, Arzo Iqbal, Georgina F. Osborne, David Howland, Andreas Neueder, Gillian P. Bates
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Edward J. Smith, Kirupa Sathasivam, Christian Landles, Georgina F. Osborne, Casandra Gomez-Paredes, Gillian P. Bates
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)