Review
Multidisciplinary Sciences
Baljit S. Khakh, Steven A. Goldman
Summary: Huntington's disease (HD) is a fatal neurodegenerative disease caused by a mutation in the huntingtin gene. Astrocytes in the striatum, a brain region affected in HD, play a role in the pathology of the disease. Dysfunctions in astrocytes contribute to cellular and metabolic abnormalities in HD, suggesting the potential for therapeutic targeting of these cells to restore normal function.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ruifang Cao, Yunchao Ling, Jiayue Meng, Ao Jiang, Ruijin Luo, Qinwen He, Anan Li, Yujie Chen, Zoutao Zhang, Feng Liu, Yixue Li, Guoqing Zhang
Summary: Understanding the relationship between fine-scale spatial organization and biological function requires an effective tool that combines spatial positions, morphological information, and spatial transcriptomics (ST) data. The Spatial Multimodal Data Browser (SMDB) is introduced as a robust web service for interactively exploring ST data by integrating multimodal data and offering customizable workspaces. It is particularly valuable in neuroscience and spatial histology studies, providing a comprehensive and efficient solution for examining the intricate relationships between spatial morphology and biological function in various tissues.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Neurosciences
Sonia Malaiya, Marcia Cortes-Gutierrez, Brian R. Herb, Sydney R. Coffey, Samuel R. W. Legg, Jeffrey P. Cantle, Carlo Colantuoni, Jeffrey B. Carroll, Seth A. Ament
Summary: Research in a Huntington's disease mouse model revealed a pattern of bidirectional dysregulation in cell type-specific genes, possibly due to partial loss-of-function of the polycomb repressive complex 2, leading to deficits in cell identity maintenance across various cell types in the adult striatum.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Clinical Neurology
Peter McColgan, Sarah Gregory, Paul Zeun, Angeliki Zarkali, Eileanoir B. Johnson, Christopher Parker, Kate Fayer, Jessica Lowe, Akshay Nair, Carlos Estevez-Fraga, Marina Papoutsi, Hui Zhang, Rachael Scahill, Sarah J. Tabrizi, Geraint Rees
Summary: McColgan et al. found that premanifest Huntington's disease gene carriers around 20 years from disease onset exhibit increased functional connectivity, which is correlated with elevated CSF neurofilament light. These changes occur in brain regions associated with gene expression specific to neuronal GABAergic and glutamatergic cells.
Article
Nutrition & Dietetics
Gabrielle R. Phillips, Sarah E. Hancock, Andrew M. Jenner, Catriona McLean, Kelly A. Newell, Todd W. Mitchell
Summary: Huntington's disease is a late-onset genetic neurodegenerative disease that leads to cognitive, motor, and psychiatric impairments. It is caused by a polyQ mutation in the HTT gene, resulting in a polyglutamine expansion in the Huntingtin protein. Changes in phospholipids in the HD brain depend on the lipid subclass, species, bond type, and location.
Article
Multidisciplinary Sciences
Rafael Alcala-Vida, Jonathan Seguin, Caroline Lotz, Anne M. Molitor, Ibai Irastorza-Azcarate, Ali Awada, Nezih Karasu, Aurelie Bombardier, Brigitte Cosquer, Jose Luis Gomez Skarmeta, Jean-Christophe Cassel, Anne-Laurence Boutillier, Thomas Sexton, Karine Merienne
Summary: This study utilizes a Huntington's mouse model to analyze the chromatin landscape in the striatum, revealing that the Huntington's mutation accelerates age-related epigenetic and transcriptional changes, and affects 3D chromatin organization locally.
NATURE COMMUNICATIONS
(2021)
Article
Clinical Neurology
S. M. Rosseto, T. A. Alarcon, D. M. C. Rocha, F. M. Ribeiro, S. S. G. Ferguson, C. Martins-Silva, M. R. Muniz, P. F. Costa, D. A. Guimaraes, Rita G. W. Pires
Summary: Huntington's disease is a neurodegenerative disorder caused by a gene expansion, characterized by motor, cognitive, and psychiatric dysfunctions. The study found that DYNLT1 gene expression was downregulated in HD patients, suggesting it could serve as a peripheral prognostic indicator for HD.
NEUROLOGICAL SCIENCES
(2021)
Article
Geriatrics & Gerontology
Emily Machiela, Paige D. Rudich, Annika Traa, Ulrich Anglas, Sonja K. Soo, Megan M. Senchuk, Jeremy M. Van Raamsdonk
Summary: This study in C. elegans models of Huntington's disease reveals that reducing mitochondrial fragmentation by targeting genes other than drp-1 can be protective and improve movement deficits, while disrupting the mitochondrial fission gene drp-1 can have detrimental effects. The research identifies novel therapeutic targets for HD aimed at enhancing mitochondrial health.
Article
Biochemistry & Molecular Biology
Sumit Jamwal, Jennifer K. Blackburn, John D. Elsworth
Summary: This study reveals sex-based and region-based variations in PON2 protein expression in the brain of African green monkeys. Female monkeys exhibit significant differences in PON2 expression levels among different brain regions, while male monkeys do not. The highest expression of PON2 protein is found in the striatum compared to other brain regions in both male and female monkeys.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Neurosciences
Julien Chambon, Pragya Komal, Gil M. Lewitus, Gina M. Kemp, Simone Valade, Houaria Adaidi, Noura Al Bistami, David Stellwagen
Summary: Huntington's disease (HD) is a neurodegenerative disease caused by a polyglutamine expansion in the huntingtin gene. Neurodegeneration in HD first occurs in the striatum, accompanied by an elevation in inflammatory cytokines. In a mouse model of HD, early changes in synaptic input onto striatal medium spiny neurons were observed, including an increase in excitatory synaptic strength and a decrease in inhibitory synaptic strength, which are both dependent on the pro-inflammatory cytokine tumor necrosis factor alpha (TNF) signaling. These changes may contribute to the development of excitotoxicity during the progress of HD.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Hyo Jung Shin, Seung Gyu Choi, Fengrui Qu, Min-Hee Yi, Choong-Hyun Lee, Sang Ryong Kim, Hyeong-Geug Kim, Jaewon Beom, Yoonyoung Yi, Do Kyung Kim, Eun-Hye Joe, Hee-Jung Song, Yonghyun Kim, Dong Woon Kim
Summary: This study investigates the role of SOX9 in reactive astrocytes following ischemic brain damage using a PLGA nanoparticle plasmid delivery system. The results demonstrate that PLGA nanoparticles can reduce ischemia-induced neurological deficits and infarct volume, providing a potential opportunity for stroke treatment.
Article
Multidisciplinary Sciences
Foteini Paraskevopoulou, Poorya Parvizi, Gokce Senger, Nurcan Tuncbag, Christian Rosenmund, Ferah Yildirim
Summary: Transcriptional dysregulation in Huntington's disease (HD) leads to functional deficits in striatal neurons. Mutant Huntingtin (Htt) decreases synaptic output of striatal neurons autonomously, with a number of dysregulated genes linked to physiological deficiencies in mutant Htt neurons. Inhibiting histone deacetylase 1/3 activities rectifies functional and morphological deficits, as well as alleviates aberrant transcriptional profiles in mutant Htt neurons.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Neurosciences
Melissa Serranilla, Melanie A. Woodin
Summary: The regulation of intracellular chloride levels is crucial for maintaining fast synaptic inhibition, which is primarily mediated by the cation-chloride cotransporters NKCC1 and KCC2. In healthy neurons, the expression of KCC2 is higher than NKCC1, resulting in lower levels of intracellular chloride. However, in immature neurons or neurological disorders, impaired KCC2 function and/or enhanced NKCC1 expression lead to chloride accumulation and GABA-mediated excitation. This review focuses on the role of chloride dysregulation in the healthy and Huntington's disease brain, with a particular emphasis on the basal ganglia circuitry and the potential therapeutic targets.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Kyle D. Ketchesin, Wei Zong, Mariah A. Hildebrand, Marianne L. Seney, Kelly M. Cahill, Madeline R. Scott, Vaishnavi G. Shankar, Jill R. Glausier, David A. Lewis, George C. Tseng, Colleen A. McClung
Summary: The human striatum is divided into different subregions with distinct molecular rhythms and core circadian clock genes showing strong phase concordance. The putamen contains a larger number of rhythmic transcripts compared to other regions, and the nucleus accumbens displays predominantly small nucleolar RNAs and long noncoding RNAs among its top rhythmic transcripts.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Minhee Jang, Jong Hee Choi, Dae Sik Jang, Ik-Hyun Cho
Summary: The neuroprotective effects of micrandilactone C (MC), a compound isolated from the roots of Schisandra chinensis, were demonstrated in animal and cell culture models of Huntington's disease (HD). MC mitigated neurological symptoms and cell death in the striatum, as well as inhibited inflammatory responses and STAT3 activation in microglia. These findings suggest that MC may be a potential therapeutic strategy for HD.
Article
Biotechnology & Applied Microbiology
Alexandre Kuhn, Yao Min Ong, Stephen R. Quake, William F. Burkholder
Letter
Biochemical Research Methods
Alexandre Kuhn
BMC BIOINFORMATICS
(2014)
Article
Biotechnology & Applied Microbiology
Alexandre Kuhn, Azad Kumar, Alexandra Beilina, Allissa Dillman, Mark R. Cookson, Andrew B. Singleton
Article
Neurosciences
Bernd Friedrich, Philipp Euler, Ruhtraut Ziegler, Alexandre Kuhn, Bernhard G. Landwehrmeyer, Ruth Luthi-Carter, Cornelius Weiller, Sabine Hellwig, Birgit Zucker
Article
Biochemistry & Molecular Biology
Elizabeth A. Thomas, Giovanni Coppola, Bin Tang, Alexandre Kuhn, SoongHo Kim, Daniel H. Geschwind, Timothy B. Brown, Ruth Luthi-Carter, Michelle E. Ehrlich
HUMAN MOLECULAR GENETICS
(2011)
Article
Neurosciences
Philipp Euler, Bernd Friedrich, Ruhtraut Ziegler, Alexandre Kuhn, Katrin S. Lindenberg, Cornelius Weiller, Birgit Zucker
NEUROSCIENCE LETTERS
(2012)
Article
Multidisciplinary Sciences
Karen N. McFarland, Sudeshna Das, Ting Ting Sun, Dmitri Leyfer, Eva Xia, Gavin R. Sangrey, Alexandre Kuhn, Ruth Luthi-Carter, Timothy W. Clark, Ghazaleh Sadri-Vakili, Jang-Ho J. Cha
Article
Multidisciplinary Sciences
Swee Jin Tan, Huan Phan, Benjamin Michael Gerry, Alexandre Kuhn, Lewis Zuocheng Hong, Yao Min Ong, Polly Suk Yean Poon, Marc Alexander Unger, Robert C. Jones, Stephen R. Quake, William F. Burkholder
Article
Multidisciplinary Sciences
Alexandre Kuhn, Yao Min Ong, Ching-Yu Cheng, Tien Yin Wong, Stephen R. Quake, William F. Burkholder
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2014)
Article
Multidisciplinary Sciences
Ke Liu, Chao Pan, Alexandre Kuhn, Adrian Pascal Nievergelt, Georg E. Fantner, Olgica Milenkovic, Aleksandra Radenovic
NATURE COMMUNICATIONS
(2019)
Article
Biotechnology & Applied Microbiology
Alexandre Kuhn, Valerie Le Fourn, Igor Fisch, Nicolas Mermod
BIOTECHNOLOGY AND BIOENGINEERING
(2020)
Article
Dentistry, Oral Surgery & Medicine
F. Momen-Heravi, R. A. Friedman, S. Albeshri, A. Sawle, M. Kebschull, A. Kuhn, P. N. Papapanou
Summary: Genome-wide transcriptomic analyses in whole tissues may not accurately identify cell type-specific information. This study utilized computational methods to decompose gene expression in gingival tissues into cell type-specific signatures, identifying differentially expressed genes and dysregulated pathways in periodontitis. Validation of these findings highlighted the potential roles of these genes in the pathogenesis of periodontitis.
JOURNAL OF DENTAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Olivier Vorlet, Lukas Neutsch, Christian Kronseder, Alexandre Kuhn
Summary: This study highlights the increasing impact of digitalization on the chemical and biotechnological industries, with Swiss Universities of Applied Sciences playing a key role in transferring academic knowledge and know-how to industrial practice. These developments, covering various digital technologies, are conducted in collaboration with industrial partners to support the growth of this important industrial sector.
Article
Nanoscience & Nanotechnology
S. M. Leitao, V. Navikas, H. Miljkovic, B. Drake, S. Marion, G. Pistoletti Blanchet, K. Chen, S. F. Mayer, U. F. Keyser, A. Kuhn, G. E. Fantner, A. Radenovic
Summary: In current nanopore-based label-free single-molecule sensing technologies, stochastic processes make it challenging to control the selection, rate, and velocity of single-molecule translocations. This study proposes a method that uses a glass nanopore mounted on a three-dimensional nanopositioner to spatially select and deterministically translocate molecules tethered on a glass surface. By controlling the distance between the nanopore and glass surface, the region of interest on the molecule can be actively selected and scanned at a controlled number of times and velocity. The method demonstrates versatility in assessing DNA-protein complexes, DNA rulers, and DNA gaps, enabling single-nucleotide gap detection.
NATURE NANOTECHNOLOGY
(2023)
Article
Neurosciences
Karen N. McFarland, Sudeshna Das, Ting Ting Sun, Dmitri Leyfer, Mee-Ohk Kim, Eva Xia, Gavin R. Sangrey, Alexandre Kuhn, Ruth Luthi-Carter, Timothy W. Clark, Ghazaleh Sadri-Vakili, Jang-Ho J. Cha
JOURNAL OF HUNTINGTONS DISEASE
(2013)
Article
Neurosciences
Nihal A. Salem, Lawrence Manzano, Michael W. Keist, Olga Ponomareva, Amanda J. Roberts, Marisa Roberto, R. Dayne Mayfield
Summary: This study identified cell-type specific gene expression changes associated with alcohol dependence in the medial prefrontal cortex of mice. The results revealed dysregulated gene co-expression networks and differentially expressed genes in multiple cell types, highlighting the involvement of inhibitory neurons and astrocytes in alcohol dependence. Novel targets for studying molecular mechanisms contributing to alcohol dependence were also identified.
NEUROBIOLOGY OF DISEASE
(2024)
Article
Neurosciences
Laura E. Hawley, Megan Stringer, Abigail J. Deal, Andrew Folz, Charles R. Goodlett, Randall J. Roper
Summary: This study found that the overexpression of DYRK1A protein in Down syndrome mice varies with age, sex, and brain region, and reducing the copy number of Dyrk1a can decrease the expression of DYRK1A. These sex-specific patterns of DYRK1A overexpression may provide mechanistic targets for therapeutic intervention in Down syndrome.
NEUROBIOLOGY OF DISEASE
(2024)