Article
Neurosciences
Carmen Nanclares, Jose Antonio Noriega-Prieto, Francisco E. Labrada-Moncada, Marija Cvetanovic, Alfonso Araque, Paulo Kofuji
Summary: Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease characterized by progressive cerebellar ataxia. This study found that the intrinsic electrical properties of Purkinje cells (PCs) in SCA1 mice were altered, and these alterations were associated with the hyperexcitability of Bergmann glia (BG). Preventing BG hyperexcitability in SCA1 mice restored the normal function of PCs.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Shelanah Salih, Zubair Ahmed Nizamudeen, Nigel De Melo, Lisa Chakrabarti, Virginie Sottile
Summary: Recent observations suggest that Bergmann glia in the cerebellum may play a role in tissue repair due to their expression of neural stem cell markers, although the physiological relevance of this overlap remains unclear in the absence of established in vivo evidence of tissue regeneration in the adult cerebellum.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Neurosciences
Shahin Shabanipour, Xiaodan Jiao, Maryam Rahimi-Balaei, Mohamad Reza Aghanoori, Seung H. Chung, Saeid Ghavami, G. Giacomo Consalez, Hassan Marzban
Summary: This study investigates the role of NCAM1 in the development of Purkinje cells (PCs). The results suggest that NCAM1 expression is significantly upregulated when PCs fail to align and instead overmigrate into the molecular layer. This may indicate that NCAM1 plays a crucial role in the migration process of PCs.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Neurosciences
Ella Borgenheimer, Katherine Hamel, Carrie Sheeler, Francisco Labrada Moncada, Kaelin Sbrocco, Ying Zhang, Marija Cvetanovic
Summary: In the early stages of SCA1 in mice, there were no changes in the proportions of neurons and glial cells in the cerebellum, but Bergmann glia, velate astrocytes, and oligodendrocytes showed profound non-cell autonomous and potentially neuroprotective reactive gene and pathway alterations in response to Purkinje cell dysfunction.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Seunghyi Kook, Ping Wang, Shufang Meng, Christopher S. Jetter, Jennifer M. S. Sucre, John T. Benjamin, Jason J. Gokey, Hayley A. Hanby, Alexa Jaume, Laura Goetzl, Michael S. Marks, Susan H. Guttentag
Summary: Lamellar bodies (LBs) are lysosome-related organelles (LROs) in AT2 cells that play a crucial role in cell homeostasis. Disruption of trafficking pathways mediated by AP-3 can lead to pulmonary fibrosis through affecting the transport of ATP8A1 to LBs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Vanessa L. Hull, Yan Wang, Travis Burns, Sarah Sternbach, Shuaishuai Gong, Jennifer McDonough, Fuzheng Guo, Laura N. Borodinsky, David Pleasure
Summary: Canavan disease is a pediatric leukodystrophy caused by mutations in the ASPA gene, resulting in a deficiency of the enzyme aspartoacylase. This leads to increased levels of N-acetyl-L-aspartate (NAA) in the brain and various neurological symptoms. In a mouse model of Canavan disease, researchers found that Bergmann glia (BG) exhibited significant morphological alterations and dysfunction, which preceded cerebellar degeneration. However, treatment with an antisense oligonucleotide targeting Nat8l, which reduces NAA production, was able to repair the BG and improve motor function. This suggests that restoring BG integrity may be a potential therapeutic strategy for Canavan disease.
Article
Multidisciplinary Sciences
Kimberly Luttik, Leon Tejwani, Hyoungseok Ju, Terri Driessen, Cleo J. L. M. Smeets, Chandrakanth Reddy Edamakanti, Aryaan Khan, Joy Yun, Puneet Opal, Janghoo Lim
Summary: Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease characterized by progressive ataxia and degeneration of specific neuronal populations. This study found that the Wnt-beta-catenin signaling pathway is progressively enhanced in the adult SCA1 mouse cerebellum and is activated in an ataxin-1 polyglutamine (polyQ) expansion-dependent manner. Activation of this pathway in astrocytes led to gliosis and disrupted Bergmann glia (BG) localization, replicating SCA1-like phenotypes in mouse models. These findings highlight the important role of BG in SCA1 pathogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Anton N. Shuvaev, Olga S. Belozor, Oleg Mozhei, Dariya A. Yakovleva, Ilya V. Potapenko, Andrey N. Shuvaev, Marina V. Smolnikova, Vladimir V. Salmin, Alla B. Salmina, Hirokazu Hirai, Anja G. Teschemacher, Sergey Kasparov
Summary: In cerebellar neurodegenerative diseases such as SCA1, reactive BG can negatively impact neuronal function and survival through compromised glutamate uptake. Excessive glutamate signaling appears to be a common feature in SCA1 pathology, contributing to cerebellar neurodegeneration.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Virology
Mohd Shariq, Asrar A. Malik, Javaid A. Sheikh, Seyed E. Hasnain, Nasreen Z. Ehtesham
Summary: SARS-CoV-2 blocks autophagosome-lysosome fusion to regulate autophagic flux, leading to accumulation of membranous vesicles. ORF3a plays a significant role in regulating autophagy by forming a complex with UV radiation resistance associated and modulating the functions of lipid kinase complexes, thereby controlling autophagosome biogenesis. ORF3a inhibits autolysosome formation by sequestering VPS39 and preventing assembly of the SNARE complex. ORF3a also promotes reticulophagy, proinflammatory responses, and ER stress by inducing the interaction between BECN1 and HMGB1, activating PIK3CA kinases, and recruits BORCS6 and ARL8B for anterograde transport of the virus.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Behavioral Sciences
Morgan E. Stevenson, Amanda S. Nazario, Alicja M. Czyz, Heather A. Owen, Rodney A. Swain
Summary: This study investigated the ultrastructural changes in the cerebellum of rats during acrobatic motor learning task training, revealing that female rats made fewer errors and had shorter latencies compared to male rats in the initial days of training. Rats that completed four days of acrobatic training showed an increase in synaptic density and astrocytic volume.
NEUROBIOLOGY OF LEARNING AND MEMORY
(2021)
Article
Cell Biology
Anton N. Shuvaev, Olga S. Belozor, Oleg Mozhei, Andrey N. Shuvaev, Yana Fritsler, Elena D. Khilazheva, Angelina Mosyagina, Hirokazu Hirai, Anja G. Teschemacher, Sergey Kasparov
Summary: Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by mutant ATXN1 protein accumulation, leading to deficits in motor performance and synaptic plasticity. The disease affects both neurons and glial cells.
Article
Multidisciplinary Sciences
Lech Kaczmarczyk, Nicole Reichenbach, Nelli Blank, Maria Jonson, Lars Dittrich, Gabor C. Petzold, Walker S. Jackson
Summary: Genetic variation is a key factor in determining phenotypic diversity, which can be minimized through inbreeding. While most disease models and transgenic tools are in C57Bl/6, caution must be exercised when generalizing results obtained with inbred strains, especially in studies involving complex phenotypes and disease models.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Jinye Dai, Christopher Patzke, Kif Liakath-Ali, Erica Seigneur, Thomas C. Sudhof
Summary: This study reveals that the binding of presynaptic neurexin-cerebellin complexes to postsynaptic GluD1 controls glutamate receptor activity in hippocampal synapses, without affecting synapse numbers. Specifically, neurexin-1-cerebellin-2 and neurexin-3-cerebellin-2 complexes regulate NMDA and AMPA receptors by activating distinct postsynaptic GluD1 effector signals.
Article
Multidisciplinary Sciences
Ann-Christin Borchers, Maren Janz, Jan-Hannes Schaefer, Arne Moeller, Daniel Kuemmel, Achim Paululat, Christian Ungermann, Lars Langemeyer
Summary: The regulation of GEF activity by Mon1 in membranes is inhibited by the N-terminal domain, resulting in alterations in endosomal structures. Mutations impairing Rab5 interaction with Mon1 lead to poor GEF activity and growth defects in endosomes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Luther J. Davis, Nicholas A. Bright, James R. Edgar, Michael D. J. Parkinson, Lena Wartosch, Judith Mantell, Andrew A. Peden, J. Paul Luzio
Summary: Our study investigated the effects of SNAREs VAMP7 and VAMP8 knockout on late endocytic organelles' tethering and pore formation, as well as the role of CHMP6 depletion in filamentous tethering between multivesicular bodies and enlarged endolysosomes. The results show the accumulation of tethered lysosome-associated membrane protein (LAMP)-carrier vesicles and 'hourglass' profiles in the absence of VAMP7 and VAMP8, and provide evidence that pore formation starts at the edge of tether arrays, with pore expansion necessary for full membrane fusion.
JOURNAL OF CELL SCIENCE
(2021)
Article
Ophthalmology
Neema Ghorbani Mojarrad, Denis Plotnikov, Cathy Williams, Jeremy A. Guggenheim, Tariq Aslam, Sarah A. Barman, Jenny H. Barrett, Paul Bishop, Peter Blows, Catey Bunce, Roxana O. Carare, Usha Chakravarthy, Michelle Chan, Sharon Y. L. Chua, David P. Crabb, Philippa M. Cumberland, Alexander Day, Parul Desai, Bal Dhillon, Andrew D. Dick, Cathy Egan, Sarah Ennis, Paul Foster, Marcus Fruttiger, John E. J. Gallacher, David F. Garway-Heath, Jane Gibson, Dan Gore, Jeremy A. Guggenheim, Chris J. Hammond, Alison Hardcastle, Simon P. Harding, Ruth E. Hogg, Pirro Hysi, Pearse A. Keane, Sir Peng T. Khaw, Anthony P. Khawaja, Gerassimos Lascaratos, Andrew J. Lotery, Tom Macgillivray, Sarah Mackie, Keith Martin, Michelle McGaughey, Bernadette McGuinness, Gareth J. Mckay, Martin McKibbin, Danny Mitry, Tony Moore, James E. Morgan, Zaynah A. Muthy, Eoin O'Sullivan, Chris G. Owen, Praveen Patel, Euan Paterson, Tunde Peto, Axel Petzold, Jugnoo S. Rahi, Alicja R. Rudnikca, Jay Self, Sobha Sivaprasad, David Steel, Irene Stratton, Nicholas Strouthidis, Cathie Sudlow, Dhanes Thomas, Emanuele Trucco, Adnan Tufail, Veronique Vitart, Stephen A. Vernon, Ananth C. Viswanathan, Cathy Williams, Katie Williams, Jayne V. Woodside, Max M. Yates, Jennifer Yip, Yalin Zheng
JAMA OPHTHALMOLOGY
(2020)
Meeting Abstract
Ophthalmology
Zara Ali, Terrance Mensah, Matthew Felgate, Robert Watt, Tasneem Z. Khatib, James R. Tribble, James E. Morgan, Keith R. Martin, Andrew Osborne
ACTA OPHTHALMOLOGICA
(2019)
Meeting Abstract
Ophthalmology
Ryan Lee Bartlett, Bethany E. Frost, Nick White, James R. Fergusson, James E. Morgan, Rachel V. North, Julie Albon
ACTA OPHTHALMOLOGICA
(2019)
Article
Ophthalmology
Heather Waterman, Simon Read, James Edwards Morgan, David Gillespie, Claire Nollett, Davina Allen, Marjorie Weiss, Pippa Anderson
BRITISH JOURNAL OF OPHTHALMOLOGY
(2020)
Article
Medicine, General & Internal
Simon Read, James Morgan, David Gillespie, Claire Nollett, Marjorie Weiss, Davina Allen, Pippa Anderson, Heather Waterman
PATIENT PREFERENCE AND ADHERENCE
(2020)
Review
Nutrition & Dietetics
Gloria Cimaglia, Marcela Votruba, James E. Morgan, Helder Andre, Pete A. Williams
Article
Ophthalmology
Pakinee Pooprasert, Dana Ahnood, Tina Parmar, Wanxin Wang, Tafadzwa Young-Zvandasara, James Morgan
Summary: This study investigated visual impairment, refractive errors, and barriers to eye care among the homeless population in Cardiff, UK. Findings show a significant disparity in ocular health, visual acuity, and refractive error compared to the general population. 50% of homeless participants had not received optometric care in the last 5 years.
Article
Ophthalmology
James R. Tribble, Eirini Kokkali, Amin Otmani, Flavia Plastino, Emma Lardner, Rupali Vohra, Miriam Kolko, Helder Andre, James E. Morgan, Pete A. Williams
Summary: Animal models of glaucoma show that unilateral or bilateral ocular hypertensive glaucoma can lead to increased neuroinflammatory responses, with more marked effects in animals with bilateral glaucoma. Unilateral glaucoma can also activate microglia in the contralateral eye, indicating the need for caution when using the contralateral eye as a control. Neuroinflammatory protein responses identified in this study may serve as potential disease-modifiable targets.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2021)
Article
Ophthalmology
James R. Tribble, Amin Otmani, Eirini Kokkali, Emma Lardner, James E. Morgan, Pete A. Williams
Summary: An inducible, magnetic bead model in Brown Norway rats was developed to replicate glaucoma features in human eyes. The model successfully demonstrated degeneration across multiple retinal ganglion cell compartments, providing a platform for testing glaucoma therapeutics.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2021)
Article
Neurosciences
Ryan J. Bevan, Tim R. Hughes, Pete A. Williams, Mark A. Good, B. Paul Morgan, James E. Morgan
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Puya Gharahkhani, Eric Jorgenson, Pirro Hysi, Anthony P. Khawaja, Sarah Pendergrass, Xikun Han, Jue Sheng Ong, Alex W. Hewitt, Ayellet Segre, John M. Rouhana, Andrew R. Hamel, Robert P. Igo, Helene Choquet, Ayub Qassim, Navya S. Josyula, Jessica N. Cooke Bailey, Pieter W. M. Bonnemaijer, Adriana Iglesias, Owen M. Siggs, Terri L. Young, Veronique Vitart, Alberta A. H. J. Thiadens, Juha Karjalainen, Steffen Uebe, Ronald B. Melles, K. Saidas Nair, Robert Luben, Mark Simcoe, Nishani Amersinghe, Angela J. Cree, Rene Hohn, Alicia Poplawski, Li Jia Chen, Shi-Song Rong, Tin Aung, Eranga Nishanthie Vithana, Gen Tamiya, Yukihiro Shiga, Masayuki Yamamoto, Toru Nakazawa, Hannah Currant, Ewan Birney, Xin Wang, Adam Auton, Michelle K. Lupton, Nicholas G. Martin, Adeyinka Ashaye, Olusola Olawoye, Susan E. Williams, Stephen Akafo, Michele Ramsay, Kazuki Hashimoto, Yoichiro Kamatani, Masato Akiyama, Yukihide Momozawa, Paul J. Foster, Peng T. Khaw, James E. Morgan, Nicholas G. Strouthidis, Peter Kraft, Jae H. Kang, Chi Pui Pang, Francesca Pasutto, Paul Mitchell, Andrew J. Lotery, Aarno Palotie, Cornelia van Duijn, Jonathan L. Haines, Chris Hammond, Louis R. Pasquale, Caroline C. W. Klaver, Michael Hauser, Chiea Chuen Khor, David A. Mackey, Michiaki Kubo, Ching-Yu Cheng, Jamie E. Craig, Stuart MacGregor, Janey L. Wiggs
Summary: The authors conducted a meta-analysis of genome-wide association studies in 34,179 cases of POAG, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities. Integration of multiple lines of genetic evidence supports the functional relevance of the identified POAG risk loci.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
R. L. Bartlett, B. E. Frost, K. E. Mortlock, J. R. Fergusson, N. White, J. E. Morgan, R. North, J. Albon
Summary: Regional axonal-related parameters in POAG patients were evaluated to study differences in optic nerve head structure at different disease stages, which were associated with visual field damage severity. Novel axon-derived indices may serve as potential biomarkers for early detection of glaucoma and identification of ONHs at risk.
SCIENTIFIC REPORTS
(2022)
Article
Clinical Neurology
Ryan J. Bevan, Pete A. Williams, Caroline T. Waters, Rebecca Thirgood, Amanda Mui, Sharon Seto, Mark Good, James E. Morgan, Marcela Votruba, Irina Erchova
BRAIN COMMUNICATIONS
(2020)
Meeting Abstract
Ophthalmology
Mukhit Kulmaganbetov, Nantheera Anantrasirichai, Alin Achim, Julie Albon, Nick White, James Edwards Morgan
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2020)
Article
Ophthalmology
Sharon Y. L. Chua, Anthony P. Khawaja, Andrew D. Dick, James Morgan, Baljean Dhillon, Andrew J. Lotery, Nicholas G. Strouthidis, Charles Reisman, Tunde Peto, Peng T. Khaw, Paul J. Foster, Praveen J. Patel
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2020)