Article
Multidisciplinary Sciences
Rebeca P. M. Santos, Roberta Ribeiro, Talita H. Ferreira-Vieira, Rosaria D. Aires, Jessica M. de Souza, Bruna S. Oliveira, Anna Luiza D. Lima, Antonio Carlos P. de Oliveira, Helton J. Reis, Aline S. de Miranda, Erica M. L. Vieira, Fabiola M. Ribeiro, Luciene B. Vieira
Summary: Obesity is a global health problem associated with metabolic dysfunctions and chronic inflammation, which can increase the risk of comorbidities such as atherosclerosis, diabetes, and insulin resistance. This study found that genetic deletion of metabotropic glutamate receptor 5 (mGluR5) can decrease body weight and visceral adiposity in BACHD mice, a mouse model of Huntington's disease with an obese phenotype, and reduce the inflammatory state in adipose tissue.
SCIENTIFIC REPORTS
(2022)
Article
Clinical Neurology
Rachel Y. Cheong, Barbara Baldo, Muhammad U. Sajjad, Deniz Kirik, Asa Petersen
Summary: The study found that early widespread central nervous system inactivation significantly improved HD-related behaviors. However, conditional circuit-wide mutant HTT deletion from the indirect striatal pathway during development and focal striatal-specific deletion in adulthood failed to rescue any of the HD-related behaviors.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Saemi Park, Shu Hon Christopher Luk, Raj S. Bains, Daniel S. Whittaker, Emily Chiem, Maria C. Jordan, Kenneth P. Roos, Cristina A. Ghiani, Christopher S. Colwell
Summary: Reducing mHTT expression in the heart benefits cardiovascular function and alleviates pathological cardiac hypertrophy and fibrosis in a Huntington's disease model.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Margarita C. Dinamarca, Laura Colombo, Natalia E. Tousiaki, Matthias Mueller, Eline Pecho-Vrieseling
Summary: Huntington's disease is a monogenic disease that disrupts neurodevelopment by altering synaptic proteins, reducing synaptic contacts, and delaying the development of mature neuronal activity patterns, supporting the presence of a neurodevelopmental component in HD.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Multidisciplinary Sciences
Hildur Soley Sveinsdottir, Amanda Decker, Christian Christensen, Pablo Botella Lucena, Haraldur Porsteinsson, Elena Richert, Valerie Helene Maier, Robert Cornell, Karl Aegir Karlsson
Summary: In this study, a novel zebrafish mutant of solute carrier 18A2 (slc18a2) was characterized, showing phenotypes partially consistent with human Parkinson's disease. The mutant exhibited changes in motility, sleep parameters, and dopamine cell number. This mutant model can be used for high throughput pharmaceutical screens and studies of monoamine transporter function.
Article
Multidisciplinary Sciences
Rana Soylu-Kucharz, Ali Khoshnan, Asa Petersen
Summary: Huntington disease is a neurodegenerative disorder caused by a genetic mutation, leading to metabolic imbalance, especially in the hypothalamus. Female mice show an obese phenotype when expressing mutant HTT in the hypothalamus, while inactivation of the IKK beta gene can inhibit weight gain.
Article
Biochemistry & Molecular Biology
Silvia Zampar, Oliver Wirths
Summary: The relationship between extracellular amyloid-beta deposits and intracellular accumulation of hyperphosphorylated tau in Alzheimer's Disease (AD) remains not fully understood. Studies have shown that A beta deposits trigger tau phosphorylation and accumulation, but the impact of different A beta variants on tau pathology is still debated. Crossbreeding studies on transgenic mouse models suggest that A beta(4-42) peptides may have partial negative effects on motor performance and spatial memory in aged mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Yehree Kim, Sang-Yeon Lee, Min Young Kim, Kyusun Park, Jin Hee Han, Jung Ho Kim, Bong Jik Kim, Byung Yoon Choi
Summary: This study established a mouse model with mutant Nlrp3 overexpression, which exhibited obvious hearing loss and developmental lag in the cochlea. By conducting histopathological analysis on this mouse model, the underlying genetic mechanism of inflammasome activation-induced hearing loss can be better understood.
FRONTIERS IN NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Elena G. Varlamova, Ekaterina V. Borisova, Yuliya A. Evstratova, Andrew G. Newman, Vera P. Kuldaeva, Maria S. Gavrish, Elena V. Kondakova, Victor S. Tarabykin, Alexey A. Babaev, Egor A. Turovsky
Summary: Epilepsy is a common neurological disease that affects both adults and infants. Recent research suggests that genetic and epigenetic factors play an important role in epileptogenesis. This article presents a newly generated mouse model of epilepsy using gene knockout and mutagenesis methods.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Gary Stanley Fernandes, Rishabh Deo Singh, Kyeong Kyu Kim
Summary: Reprogramming astrocytes into neurons using a novel chemical-based approach offers a promising therapeutic approach for neurodegenerative diseases. In this study, a chemical mixture was developed to rapidly and efficiently induce the neural reprogramming of astrocytes into neurons, with a conversion efficiency of 82 +/- 6%. The induced cells demonstrated neuronal functionality, confirming their potential in clinical applications.
Article
Medicine, Research & Experimental
Deanna M. Marchionini, Jeh-Ping Liu, Alberto Ambesi-Impiombato, Kimberly Kerker, Kim Cirillo, Mukesh Bansal, Rich Mushlin, Daniela Brunner, Sylvie Ramboz, Mei Kwan, Kirsten Kuhlbrodt, Karsten Tillack, Finn Peters, Leena Rauhala, John Obenauer, Jonathan R. Greene, Christopher Hartl, Vinod Khetarpal, Brenda Lager, Jim Rosinski, Jeff Aaronson, Morshed Alam, Ethan Signer, Ignacio Munoz-Sanjuan, David Howland, Scott O. Zeitlin
Summary: A mouse model of Huntington's disease with temporal control of mutant huntingtin expression was developed. Moderate lowering of mutant huntingtin delayed behavioral dysfunction and protein aggregation, but the benefits diminished over time. Early lowering of mutant huntingtin improved transcriptional dysregulation, while late lowering had no effect. Only early lowering delayed the elevation of neurofilament light chain. These findings have implications for future therapeutic strategies.
Article
Medicine, Research & Experimental
James P. Orengo, Larissa Nitschke, Meike E. van der Heijden, Nicholas A. Ciaburri, Harry T. Orr, Huda Y. Zoghbi
Summary: Spinocerebellar ataxia type 1 (SCA1) is an adult-onset neurodegenerative disorder characterized by the dysfunction of motor neurons, leading to the inability to maintain proper respiratory function. However, restricting the expression of the pathogenic SCA1 allele in motor neurons alone is not sufficient to cause premature death.
Article
Cell Biology
Raquel Garcia-Lopez, Ana Pombero, Alicia Estirado, Emilio Geijo-Barrientos, Salvador Martinez
Summary: Our study suggests that deleting the first coding exon of the Lis1 gene may cause cortical anomalies associated with the pathophysiology of schizophrenia. The Lis1/sLis1 murine model shows abnormal neuronal morphology and enhanced cortical excitability.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jurgen Wess
Summary: Beta-arrestins play a dual role as inhibitors of signaling via G protein-coupled receptors and as signaling molecules themselves. Despite their structural and sequence homology, beta-arrestin-1 and -2 have distinct and non-redundant functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
H. E. AlQot, R. J. Rylett
Summary: Acetylcholine synthesizing enzyme choline acetyltransferase (ChAT) is reduced in aging and Alzheimer's disease. 82-kDa ChAT, expressed only in primates, exhibits a change in subcellular distribution with age and AD, and may play a role in gene expression during cellular stress. A transgenic mouse model expressing human 82-kDa ChAT was developed to study its impact in cholinergic neuron vulnerability and dysfunction.
SCIENTIFIC REPORTS
(2023)
Article
Clinical Neurology
B. Baldo, S. Gabery, R. Soylu-Kucharz, R. Y. Cheong, J. B. Henningsen, E. Englund, C. McLean, D. Kirik, G. Halliday, A. Petersen
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Diana Wiesner, Jerome Sinniger, Alexandre Henriques, Stephane Dieterle, Hans-Peter Mueller, Volker Rasche, Boris Ferger, Sylvie Dirrig-Grosch, Rana Soylu-Kucharz, Asa Petersen, Paul Walther, Birgit Linkus, Jan Kassubek, Philip C. Wong, Albert C. Ludolph, Luc Dupuis
HUMAN MOLECULAR GENETICS
(2015)
Article
Multidisciplinary Sciences
Rana Soylu-Kucharz, Barbara Baldo, Asa Petersen
SCIENTIFIC REPORTS
(2016)
Article
Multidisciplinary Sciences
Rana Soylu-Kucharz, Asa Sandelius, Marie Sjoegren, Kaj Blennow, Edward J. Wild, Henrik Zetterberg, Maria Bjoerkqvist
SCIENTIFIC REPORTS
(2017)
Article
Biology
Mette Mathiesen Janiurek, Rana Soylu-Kucharz, Christina Christoffersen, Krzysztof Kucharz, Martin Lauritzen
Article
Neurosciences
Marie Sjogren, Rana Soylu-Kucharz, Unali Dandunna, Tiberiu Loredan Stan, Michele Cavalera, Asa Sandelius, Henrik Zetterberg, Maria Bjorkqvist
NEUROBIOLOGY OF DISEASE
(2019)
Article
Multidisciplinary Sciences
Tiberiu Loredan Stan, Rana Soylu-Kucharz, Stephen Burleigh, Olena Prykhodko, Ling Cao, Naomi Franke, Marie Sjogren, Caroline Haikal, Frida Hallenius, Maria Bjorkqvist
SCIENTIFIC REPORTS
(2020)
Article
Multidisciplinary Sciences
Osama Elabi, Abderahim Gaceb, Robert Carlsson, Thomas Padel, Rana Soylu-Kucharz, Irene Cortijo, Wen Li, Jia-Yi Li, Gesine Paul
Summary: The pathological hallmark of Parkinson's disease is the formation of Lewy bodies containing alpha-synuclein, but microvascular alterations have also been linked to neurodegeneration in PD. Using a human alpha-synuclein overexpression mouse model, researchers demonstrated compromised blood-brain barrier integrity, dynamic changes in vessel morphology, and activation of pericytes, supporting the occurrence of vascular pathology as an important aspect in PD. This model provides a powerful tool to investigate disease-modifying factors and guide the development of new treatments for Parkinson's disease.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Jo B. Henningsen, Rana Soylu-Kucharz, Maria Bjorkqvist, Asa Petersen
Summary: Huntington disease is a fatal neurodegenerative movement disorder caused by a mutant huntingtin protein. Despite certain brain regions being affected, the role of excitotoxicity in the loss of hypothalamic neuronal populations in HD remains unclear. Further research is needed to understand the underlying mechanisms of selective vulnerability of certain neurons in HD.
Article
Multidisciplinary Sciences
Rana Soylu-Kucharz, Ali Khoshnan, Asa Petersen
Summary: Huntington disease is a neurodegenerative disorder caused by a genetic mutation, leading to metabolic imbalance, especially in the hypothalamus. Female mice show an obese phenotype when expressing mutant HTT in the hypothalamus, while inactivation of the IKK beta gene can inhibit weight gain.
Article
Endocrinology & Metabolism
Elna Dickson, Rana Soylu-Kucharz, Asa Petersen, Maria Bjorkqvist
Summary: This study aimed to investigate the effects of hypothalamic huntingtin (HTT) protein levels on metabolic phenotype and disease features in Huntington's disease (HD). The results showed that hypothalamic overexpression of mutant HTT led to weight gain, particularly in the early stages of the disease, accompanied by behavioral alterations and transcriptional changes.
MOLECULAR METABOLISM
(2022)
Article
Neurosciences
Elna Dickson, Amoolya Sai Dwijesha, Natalie Andersson, Sofia Lundh, Maria Bjorkqvist, Asa Petersen, Rana Soylu-Kucharz
Summary: This study investigated the transcriptional changes caused by hypothalamic expression of huntingtin (HTT) gene in Huntington's disease (HD). The results showed that both wild-type HTT (wtHTT) and mutant HTT (mHTT) overexpression altered the hypothalamic transcriptome profile, with mHTT specifically affecting neuroendocrine circuits. However, the ubiquitous expression of full-length mHTT in the BACHD mouse model moderately affected the transcriptomic profile.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Geriatrics & Gerontology
Oleg Zhukov, Chen He, Rana Soylu-Kucharz, Changsi Cai, Andreas D. Lauritzen, Blanca Irene Aldana, Maria Bjorkqvist, Martin Lauritzen, Krzysztof Kucharz
Summary: Using two-photon microscopy and microscopy, this study observed the function of cerebral vasculature and neurovascular coupling in an AD mouse model. The results showed that the blood-brain barrier and neurovascular coupling were preserved, and the density of capillary pericytes was not affected. These findings suggest that microvascular function is preserved in the 5xFAD mice and highlight the importance of choosing appropriate preclinical models of AD.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Cansu Ozdemir, Duygu Akcay, Digdem Yoyen-Ermis, Ekim Zihni Taskiran, Rana Soylu-Kucharz, Guenes Esendagli, Yusuf Cetin Kocaefe
Summary: Chronic skeletal muscle degeneration is characterized by fiber atrophy accompanied by deposition of extracellular matrix (ECM) components and fatty infiltration. Excessive accumulation of ECM leads to fibrosis via the contribution of fibro-adipogenic precursors (FAPs). Fibrosis also accompanies disuse atrophy and sarcopenia without significant inflammation.
Article
Neurosciences
Elna Dickson, Claes Fryklund, Rana Soylu-Kucharz, Marie Sjogrena, Karin G. Stenkula, Maria Bjorkqvista
Summary: The present study investigates the molecular and functional changes in white adipose tissue (WAT) that occur at weight loss in R6/2 mice. The study found early sex-specific changes in adipocyte cell size distribution in WAT of R6/2 and leptin-deficient R6/2 mice. Female mice had a reduction in body weight accompanied by an increased proportion of smaller adipocytes, while male mice displayed a shift towards larger adipocyte sizes without significant body weight reduction.
JOURNAL OF HUNTINGTONS DISEASE
(2023)