Article
Biochemistry & Molecular Biology
Rosalia Bruno, Geraldina Riccardi, Floriana Iacobone, Flavia Chiarotti, Laura Pirisinu, Ilaria Vanni, Stefano Marcon, Claudia D'Agostino, Matteo Giovannelli, Piero Parchi, Umberto Agrimi, Romolo Nonno, Michele Angelo Di Bari
Summary: This study investigated the relationship between prion strains and astrocyte phenotype in six human- and animal-vole-adapted strains. The results showed that astrocyte morphology and astrocyte-associated PrPSc deposition varied depending on the strain, indicating strain-specific phenotypes of reactive astrocytes. Additionally, astrocyte-associated PrPSc deposition was observed in four out of six strains and correlated with astrocyte size.
Article
Cardiac & Cardiovascular Systems
Eva Querdel, Marina Reinsch, Liesa Castro, Deniz Kose, Andrea Bahr, Svenja Reich, Birgit Geertz, Barbel Ulmer, Mirja Schulze, Marc D. Lemoine, Tobias Krause, Marta Lemme, Jascha Sani, Aya Shibamiya, Tim Stuedemann, Maria Koehne, Constantin von Bibra, Nadja Hornaschewitz, Simon Pecha, Yusuf Nejahsie, Ingra Mannhardt, Torsten Christ, Hermann Reichenspurner, Arne Hansen, Nikolai Klymiuk, M. Krane, C. Kupatt, Thomas Eschenhagen, Florian Weinberger
Summary: The transplantation of engineered heart tissue (EHT) patches resulted in partial remuscularization of the injured heart and improved left ventricular function in a dose-dependent manner in guinea pig and pig models. Human-scale patches were successfully transplanted onto pigs in a proof-of-principle study.
Article
Gastroenterology & Hepatology
Zhen-Xing Liang, Hua-Shan Liu, Li Xiong, Zi-Wei Zeng, Xiao-Bin Zheng, Liang Kang, Ping Lan, Xian-Rui Wu
Summary: The study revealed the heterogeneity in ADSCs, with CD200(+) ADSCs presenting as an alternative treatment for IBD. CD200(+) ADSCs effectively reduced intestinal inflammation in IBD models by promoting macrophage M2 polarization, suggesting their potential therapeutic value for IBD.
JOURNAL OF CROHNS & COLITIS
(2023)
Review
Biochemistry & Molecular Biology
Baiyan Ren, Anna Dunaevsky
Summary: Astrocytes, a subtype of glial cells in the central nervous system, exhibit morphological and functional diversity; human pluripotent stem cell differentiation approaches play an important role in studying the etiology of neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Jenny Lange, Olivia Gillham, Michael Flower, Heather Ging, Simon Eaton, Sneha Kapadia, Andreas Neueder, Michael R. Duchen, Patrizia Ferretti, Sarah J. Tabrizi
Summary: Huntington's Disease is a neurodegenerative disease caused by a genetic mutation. Astrocyte dysfunction, specifically changes in gene expression and metabolic activity, plays a role in the pathogenesis of the disease. Additionally, all Huntington's Disease astrocytes exhibit increased DNA damage and a DNA damage response, suggesting a potential mechanism for their dysfunction.
PROGRESS IN NEUROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Mandeep Kumar, Nhung Thi Phuong Nguyen, Marco Milanese, Giambattista Bonanno
Summary: Astrocytes play a crucial role in neurodegenerative disorders, and the differentiation of human iPSCs into astrocytes has opened up new possibilities for disease modeling and drug screening. This advancement in research offers a promising avenue for exploring treatment strategies for neurodegenerative diseases.
Article
Cell Biology
Jinghui Lei, Xiaoyu Jiang, Daoyuan Huang, Ying Jing, Shanshan Yang, Lingling Geng, Yupeng Yan, Fangshuo Zheng, Fang Cheng, Weiqi Zhang, Juan Carlos Izpisua Belmonte, Guang-Hui Liu, Si Wang, Jing Qu
Summary: Using CRISPR/Cas9 gene editing, researchers investigated the response mechanism of human vascular cells to HIF-1α under hypoxic conditions. They found that HIF-1α plays an important role in promoting ischemic vascular regeneration and that MSCs are particularly susceptible to HIF-1α deficiency. Transcriptional inactivation of ANKZF1, an effector of HIF-1α, was found to impair pro-angiogenic processes.
Article
Cell Biology
Taryn E. Murray, Tyler J. Wenzel, Svetlana Simtchouk, Bridget K. Greuel, Julien Gibon, Andis Klegeris
Summary: The study reveals that cardiolipin (CL) can modulate the secretion and phagocytic activity of astrocytes, potentially through interaction with TLR 4, expanding our understanding of CL's role in neuroimmune responses.
MEDIATORS OF INFLAMMATION
(2022)
Review
Immunology
Nina Stoberl, Emily Maguire, Elisa Salis, Bethany Shaw, Hazel Hall-Roberts
Summary: Neuroinflammation is a complex biological process involving microglia and astrocytes that plays a significant role in brain disorders. Various iPSC models have been used to study neuroinflammation, and different stimuli have been established to induce inflammatory responses.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Oncology
Marc Richard Kolbe, Tim Hohmann, Urszula Hohmann, Chalid Ghadban, Ken Mackie, Christin Zoeller, Julian Prell, Joerg Illert, Christian Strauss, Faramarz Dehghani
Summary: Glioblastoma (GBM) is the most common malignant brain tumor in humans with a median survival time of less than 15 months. Cannabinoids, such as THC and CBD, have shown therapeutic potential by binding to specific receptors like GPR55, suggesting a promising alternative treatment option for GBM patients.
Article
Cell Biology
Maria Luengo-Mateos, Antia Gonzalez-Vila, Nathalia Romanelli Vicente Dragano, Nataliia Ohinska, Maria Silveira-Loureiro, Marco Gonzalez-Dominguez, Anxela Estevez-Salguero, Paula Novelle-Rodriguez, Miguel Lopez, Olga Barca-Mayo
Summary: Here, we show that hypothalamic astrocytic BMAL1 plays a role in computing cyclic metabolic information for optimizing energetic resources in a sexually dimorphic manner. Knockdown of BMAL1 in female astrocytes leads to negative energy balance and alters basal metabolic cycles without affecting circadian locomotor activity. Furthermore, female mice with BMAL1 knockdown in astrocytes exhibit a male-like metabolic obese phenotype when fed a high-fat diet. These findings highlight the importance of astrocytic BMAL1 in the regulation of energy homeostasis and its potential implications in the physiopathology of obesity and related comorbidities.
Article
Anatomy & Morphology
Zhijie Liang, Donglin Huang, Wenhai Nong, Jinping Mo, Dandan Zhu, Mengxin Wang, Maojian Chen, Changyuan Wei, Hongmian Li
Summary: This study aimed to identify the optimal concentrations of A-PRFe to promote adipogenic and osteogenic differentiation of human adipose-derived stem cells (ASCs). Results showed that A-PRFe significantly stimulated ASC proliferation and enhanced adipogenic/osteogenic differentiation and paracrine function at higher concentrations.
Article
Chemistry, Multidisciplinary
Sophia Shaka, Nicholas Carpo, Victoria Tran, Araceli Espinosa-Jeffrey
Summary: Human neural stem cells flown into space were successfully induced into astrocytes after a slow process lasting several weeks, showing slow but significant proliferation and a tendency to continue proliferating at the same pace. Astrocytes, a major type of glial cells, are crucial for the normal function of the central nervous system and are increasingly recognized as a critical component in most neurodegenerative diseases. Understanding the effects of space microgravity on astrocytes is essential for long-duration space travel.
APPLIED SCIENCES-BASEL
(2021)
Article
Immunology
Michael MacLean, Judyta Juranek, Swetha Cuddapah, Raquel Lopez-Diez, Henry H. Ruiz, Jiyuan Hu, Laura Frye, Huilin Li, Paul F. Gugger, Ann Marie Schmidt
Summary: The study demonstrates the significant role of microglia RAGE in the progression of ALS pathology, showing that microglia Ager deletion can extend survival in male SOD1(G93A) mice and ameliorate certain pathways identified in human ALS patients.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Neurosciences
Ulla-Kaisa Peteri, Juho Pitkonen, Kagistia Hana Utami, Jere Paavola, Laurent Roybon, Mahmoud A. Pouladi, Maija L. Castren
Summary: The study established a method to generate human astrocytes from hPSCs with forebrain patterning and CNTF, confirming activation of forebrain differentiation pathways at D30 and D60 of differentiation in vitro. The reproducibility of the method across multiple hPSC lines and the usefulness of forebrain astrocyte modeling in research investigating forebrain pathology were demonstrated. Intracellular calcium responses to ATP indicated differentiation of the functional astrocyte population with specific gene expressions.
Article
Biochemistry & Molecular Biology
Marrit Putker, David C. S. Wong, Estere Seinkmane, Nina M. Rzechorzek, Aiwei Zeng, Nathaniel P. Hoyle, Johanna E. Chesham, Mathew D. Edwards, Kevin A. Feeney, Robin Fischer, Nicolai Peschel, Ko-Fan Chen, Michael Vanden Oever, Rachel S. Edgar, Christopher P. Selby, Aziz Sancar, John S. O'Neill
Summary: CRY proteins are considered essential components of the cellular clock mechanism, but studies show that circadian rhythms can still exist in the absence of CRY, albeit with variable expression and shorter periods. The classic circadian hallmarks like temperature compensation and period determination by specific activities are maintained even without CRY-mediated feedback repression. The sustained PER2 protein rhythms and circadian variation in protein stability suggest a post-translational core mechanism for biological clocks.
Article
Clinical Neurology
James J. M. Loan, Angus B. Gane, Laura Middleton, Brendan Sargent, Tom James Moullaali, Mark A. Rodrigues, Laura Cunningham, Joanna Wardlaw, Rustam Al-Shahi Salman, Neshika Samarasekera
Summary: This study investigated the association between peri-hematomal edema and intracerebral hemorrhage volume with one-year functional outcome and long-term survival in spontaneous intracerebral hemorrhage patients. The results showed that intracerebral hemorrhage volume and total lesion volume were independently associated with death or dependence one year after intracerebral hemorrhage, while peri-hematomal edema volume was not.
INTERNATIONAL JOURNAL OF STROKE
(2021)
Article
Clinical Neurology
Jean-Yves Douet, Alvina Huor, Herve Cassard, Severine Lugan, Naima Aron, Mark Arnold, Didier Vilette, Juan-Maria Torres, James W. Ironside, Olivier Andreoletti
Summary: Sporadic Creutzfeldt-Jakob disease (sCJD) typically occurs in the central nervous system, but recent research has shown prion infectivity detected in peripheral tissues of patients as well. Although infectivity levels varied unpredictably among different patients and tissues, these findings may alter our perception of transmission risks associated with sCJD.
ACTA NEUROPATHOLOGICA
(2021)
Article
Biochemistry & Molecular Biology
Debosmita Sardar, Brittney Lozzi, Junsung Woo, Teng-Wei Huang, Caroline Cvetkovic, Chad J. Creighton, Robert Krencik, Benjamin Deneen
Summary: This study explores how neuronal-derived signals influence astrocyte function at the gene expression level, highlighting distinct transcriptomic and chromatin accessibility changes in response to different neuroactive compounds. Noradrenaline shows a more profound effect on astrocyte transcriptional profiles compared to other neurotransmitters, indicating potential dysregulated genetic mechanisms of astrocyte-neuron communication in neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Nan Zhang, Brittani Bewick, Jason Schultz, Anjana Tiwari, Robert Krencik, Aijun Zhang, Kaho Adachi, Guangbin Xia, Kyuson Yun, Partha Sarkar, Tetsuo Ashizawa
Summary: A DNAzyme has been developed to efficiently destroy expanded CAG repeat RNA in various polyQ diseases, showing allele-specific cleavage in SCA1 cells and improved cell viability in SCA3 cells without affecting mitochondrial metabolism or aggresome formation. The stable presence of DNAzyme in mouse brain for at least 1 month and its significant reduction of high molecular weight ATXN3 proteins in a SCA3 mouse model suggest its potential as an effective RNA silencing molecule for multiple polyQ diseases.
Article
Chemistry, Multidisciplinary
Assaf Zinger, Caroline Cvetkovic, Manuela Sushnitha, Tomoyuki Naoi, Gherardo Baudo, Morgan Anderson, Arya Shetty, Nupur Basu, Jennifer Covello, Ennio Tasciotti, Moran Amit, Tongxin Xie, Francesca Taraballi, Robert Krencik
Summary: Nanovesicles (NVs) engineered with membrane proteins from human pluripotent stem cell-derived neurons have been shown to improve biocompatibility, enhance neuronal association and uptake, and hold potential for promoting neuroregeneration. These customizable NVs present a promising approach for next-generation theranostics in neural regeneration.
Article
Instruments & Instrumentation
Samira Aghlara-Fotovat, Amanda Nash, Boram Kim, Robert Krencik, Omid Veiseh
Summary: This article highlights the importance of interactions between host immune cells and the extracellular matrix, discusses potential diseases caused by immune system dysregulation, and proposes therapeutic strategies to restore tissue balance.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2021)
Article
Neurosciences
Jean-Yves Douet, Alvina Huor, Herve Cassard, Severine Lugan, Naima Aron, Chloe Mesic, Didier Vilette, Tomas Barrio, Nathalie Streichenberger, Armand Perret-Liaudet, Marie-Bernadette Delisle, Patrice Peran, Jean-Philippe Deslys, Emmanuel Comoy, Jean-Luc Vilotte, Katayoun Goudarzi, Vincent Beringue, Marcelo A. Barria, Diane L. Ritchie, James W. Ironside, Olivier Andreoletti
Summary: The treatment with human pituitary-derived growth hormone (hGH) was responsible for a significant proportion of iatrogenic Creutzfeldt-Jakob disease (iCJD) cases, with France and the UK experiencing the largest numbers. Differences in PRNP codon 129 polymorphisms and estimated incubation periods did not lead to significant differences in the prion strains identified in hGH-iCJD cases from the two countries.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
David C. S. Wong, Estere Seinkmane, Aiwei Zeng, Alessandra Stangherlin, Nina M. Rzechorzek, Andrew D. Beale, Jason Day, Martin Reed, Sew Y. Peak-Chew, Christine T. Styles, Rachel S. Edgar, Marrit Putker, John S. O'Neill
Summary: The study suggests that CRY proteins play a crucial role in maintaining protein and osmotic homeostasis against daily perturbation instead of causing large-scale daily variation in proteome composition. CRY-deficient cells show differences in temporal variation compared to wild-type cells and are more susceptible to proteotoxic stress.
Article
Cell Biology
Caroline Cvetkovic, Rajan Patel, Arya Shetty, Matthew K. Hogan, Morgan Anderson, Nupur Basu, Samira Aghlara-Fotovat, Srivathsan Ramesh, Debosmita Sardar, Omid Veiseh, Michael E. Ward, Benjamin Deneen, Philip J. Horner, Robert Krencik
Summary: The study reveals that activation of Gq-GPCR in astrocytes leads to an increase in intracellular calcium and induction of immediate early genes and thrombospondin 1. Additionally, astrocytes also undergo NF-kappa B nuclear translocation and secretion of inflammatory proteins, resulting in a decreased firing rate of cocultured neurons.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Neurosciences
Marco Zattoni, Marika Mearelli, Silvia Vanni, Arianna Colini Baldeschi, Thanh Hoa Tran, Chiara Ferracin, Marcella Catania, Fabio Moda, Giuseppe Di Fede, Giorgio Giaccone, Fabrizio Tagliavini, Gianluigi Zanusso, James W. Ironside, Isidre Ferrer, Giuseppe Legname
Summary: This study investigated the differential expression of serpin superfamily members in neurodegenerative diseases. The results showed dysregulation of SERPINB1, SERPINB6, SERPING1, SERPINH1, and SERPINI1 in sCJD individuals compared to controls, while only SERPINB1 was upregulated in AD patients. Additionally, SerpinA3n transcript and protein were upregulated in a mouse model of AD. These findings suggest that SERPINA3/SerpinA3n may be a potential therapeutic target for the treatment of prion and prion-like neurodegenerative diseases.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Clinical Neurology
Nina M. Rzechorzek, Michael J. Thrippleton, Francesca M. Chappell, Grant Mair, Ari Ercole, Manuel Cabeleira, Jonathan Rhodes, Ian Marshall, John S. O'Neill
Summary: Temperature-based treatment after brain injury is controversial due to the undefined 'normal' human brain temperature. A study shows that human brain temperature exceeds body temperature by 2-3 degrees C and varies by age, sex, brain region, and time. Loss of daily brain temperature rhythm predicts death after traumatic brain injury. This study aimed to determine the clinical relevance of brain temperature in patients and analyzed the variations in healthy adults' brain temperature.
Review
Cell Biology
Samantha L. Eaton, Fraser Murdoch, Nina M. Rzechorzek, Gerard Thompson, Claudia Hartley, Benjamin Thomas Blacklock, Chris Proudfoot, Simon G. Lillico, Peter Tennant, Adrian Ritchie, James Nixon, Paul M. Brennan, Stefano Guido, Nadia L. Mitchell, David N. Palmer, C. Bruce A. Whitelaw, Jonathan D. Cooper, Thomas M. Wishart
Summary: The impact of neurological disorders is globally recognized, and the translation from rodent-derived therapeutics to human neurological interventions is challenging. In order to improve translation, higher order mammals with complex neuroanatomy, such as livestock, are being used. We provide comprehensive neurological assessment protocols for large animal species to standardize the characterization of these models and recommend their use in neurological clinical scoring.
Article
Genetics & Heredity
Alexander G. Murley, Yu Nie, Zoe Golder, Michael John Keogh, Colin Smith, James W. Ironside, Patrick F. Chinnery
Summary: This study investigated the role of pathologic somatic variants in the PRNP gene in sporadic Creutzfeldt-Jakob disease (sCJD). High-depth amplicon-based sequencing was performed on postmortem brain tissue from sCJD, Alzheimer's disease, and control subjects. The study found somatic PRNP variants in sCJD cases, but their pathogenicity remains uncertain.
NEUROLOGY-GENETICS
(2023)
Article
Multidisciplinary Sciences
Joseph L. Watson, Estere Seinkmane, Christine T. Styles, Andrei Mihut, Lara K. Kruger, Kerrie E. Mcnally, Vicente Jose Planelles-Herrero, Michal Dudek, Patrick M. Mccall, Silvia Barbiero, Michael Vanden Oever, Sew Yeu Peak-Chew, Benjamin T. Porebski, Aiwei Zeng, Nina M. Rzechorzek, David C. S. Wong, Andrew D. Beale, Alessandra Stangherlin, Margot Riggi, Janet Iwasa, Jorg Morf, Christos Miliotis, Alina Guna, Alison J. Inglis, Jan Brugues, Rebecca M. Voorhees, Joseph E. Chambers, Qing-Jun Meng, John S. O'Neill, Rachel S. Edgar, Emmanuel Derivery
Summary: The availability of water is crucial for optimum protein function and biochemical activity. In concentrated macromolecular solutions, modest changes in temperature have a significant impact on water potential, but this effect is counteracted by changes in osmotic strength. This duality of temperature and osmotic strength allows for simple manipulation of solvent thermodynamics to prevent cell death under extreme cold or heat shock. Water potential-driven changes in macromolecular assembly, particularly biomolecular condensation, rapidly compensate for osmotic and thermal fluctuations in the cytoplasm, ensuring water availability.