Article
Immunology
Romain Troubat, Samuel Leman, Katleen Pinchaud, Alexandre Surget, Pascal Barone, Sebastien Roger, Anne-Marie Le Guisquet, Bruno Brizard, Catherine Belzung, Vincent Camus
Summary: After exposure to UCMS, P2X7R KO mice showed significant differences in behavioral and neurogenesis compared to the control group, as well as notable changes in the density of brain immune cells. The recruitment rate of peripheral immune cells was unaffected by P2X7R gene expression or antidepressant treatment.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Multidisciplinary Sciences
J. Jason McAnany, Nathanael Matei, Yi-Fan Chen, Karen Liu, Jason C. Park, Mahnaz Shahidi
Summary: The study found significant differences in rod-pathway function between 5xFAD and WT mice, with cone-pathway function being less affected. This suggests that retinal electrophysiology may be a useful tool for evaluating neural dysfunction in AD.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Renee Chasse, Alexey Malyshev, Roslyn Holly Fitch, Maxim Volgushev
Summary: Theoretical and modeling studies suggest that heterosynaptic plasticity enhances discriminative learning and repetitive learning in Hebbian-type systems. Experimental manipulation of adenosine A1 receptors (A1Rs) to impair heterosynaptic plasticity resulted in impaired synaptic plasticity and deficits in visual discrimination learning in A1R KO mice. These results provide experimental evidence for the role of heterosynaptic plasticity in organism-level learning and suggest it as a potential target for interventions to enhance new learning.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Susanne Wiemann, Aisha Yousf, Stephanie C. Joachim, Carolin Peters, Ana M. Mueller-Buehl, Natalie Wagner, Jacqueline Reinhard
Summary: This study aimed to investigate the functional role of the glycoprotein tenascin-C (Tnc) in retinal ischemia, finding increased Tnc levels after ischemia accompanied by diminished rod-photoreceptor degeneration and retinal dysfunction in KO mice. Additionally, KO mice showed lower levels of activated caspase 3(+) cells, suggesting a potential role of Tnc in synaptic remodeling during ischemic retinal degeneration. Increased vesicular glutamate transporter 1 (vGlut1) levels in both ischemic groups indicated impaired glutamatergic signaling and excitotoxicity after ischemia.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Pharmacology & Pharmacy
Abtar Mishra, Assirbad Behura, Ashish Kumar, Lincoln Naik, Ashapoorna Swain, Mousumi Das, Suman Sudha Sarangi, Puja Dokania, Vijaya R. Dirisala, Sujit K. Bhutia, Amit Mishra, Ramandeep Singh, Rohan Dhiman
Summary: The P2X7 receptor is a key player in various physiological processes and has been directly associated with several pathophysiological conditions. Understanding its structure and downstream signaling processes is considered a promising approach to alleviate the afflictions associated with disorders like cancer, diabetes, arthritis, tuberculosis, and inflammatory diseases.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Genetics & Heredity
Adam J. Lawther, Jerzy Zieba, Zhiming Fang, Teri M. Furlong, Illya Conn, Hemna Govindaraju, Laura L. Y. Choong, Nigel Turner, Khawar Sohail Siddiqui, Wallace Bridge, Sam Merlin, Tzipi Cohen Hyams, Murray Killingsworth, Valsamma Eapen, Raymond A. Clarke, Adam K. Walker
Summary: Mitochondrial dysfunction is strongly associated with autism spectrum disorder (ASD), and the IMMP2L gene is linked to autism inheritance. By developing an Immp2lKD knockout mouse model, the researchers found that Immp2l(KD) -/- KO mice did not show any differences in the core behavioral symptoms of ASD, but they exhibited increased auditory stimulus-driven instrumental behavior and amphetamine-induced locomotion. The researchers also discovered that the ROS levels were lowered in the new Immp2l(KD) -/- KO mice, contrary to previous studies on Immp2l-deficient mouse models, and these mice did not display oxidative stress-related phenotypes.
Article
Biology
Karoline B. Rypdal, A. Olav Melleby, Emma L. Robinson, Jia Li, Sheryl Palmero, Deborah E. Seifert, Daniel Martin, Catelyn Clark, Begona Lopez, Kristine Andreassen, Christen P. Dahl, Ivar Sjaastad, Theis Tonnessen, Mathis K. Stokke, William E. Louch, Arantxa Gonzalez, Stephane Heymans, Geir Christensen, Suneel S. Apte, Ida G. Lunde
Summary: Heart failure is a significant global cause of disease and death, characterized by cardiac remodeling due to pressure overload. This study demonstrates that ADAMTSL3 regulates TGF beta in the heart and may have beneficial effects on heart failure.
COMMUNICATIONS BIOLOGY
(2022)
Article
Psychiatry
Sandra T. Suess, Linda M. Olbricht, Stefan Herlitze, Katharina Spoida
Summary: In this study, the researchers used a 5-HT2CR knock-out mouse model to investigate the role of 5-HT2CRs in the fear circuitry. The results showed that the loss of 5-HT2CRs exclusively accelerated fear extinction without affecting fear acquisition and fear expression. They also discovered alterations in neuronal activity in specific subregions of the DRN and the BNST in the knock-out mice. Additionally, they identified a specific serotonergic pathway from the DRC to the BNSTad that showed increased neuronal activity in the knock-out mice. These findings provide new insights into the fear extinction network and have important implications for the treatment of PTSD.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Neurosciences
Annia Abtout, Gordon Fain, Jurgen Reingruber
Summary: This study analyzed the contribution of various biological processes in the photoreceptor light response, finding that the shape of the response is controlled by deactivation parameters, while activation parameters scale the shape and affect the amplitude. The rising phase of the response is shown to depend on Ca2+ feedback, contrary to previous belief. New methods were devised to extract activation and deactivation rates from the analysis of response shape and amplitude.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Medicine, General & Internal
Camilo Toledo, Esteban Diaz-Jara, Hugo S. Diaz, Karla G. Schwarz, Katherin Pereyra, Alexandra Las Heras, Angelica Rios-Gallardo, David C. Andrade, Thiago Moreira, Ana Takakura, Noah J. Marcus, Rodrigo Del Rio
Summary: This study found that RTN astrocytes play a pivotal role in the generation and maintenance of breathing disorders (BD) in chronic heart failure (CHF) patients through the mechanism of P2X7 receptor (P2X7r) signaling. The activity and ATP bioavailability of RTN astrocytes were reduced in CHF patients, and restoring normal astrocyte activity and ATP levels improved breathing regularity in CHF. Additionally, delivering human P2X7 receptor into astrocytes increased ATP bioavailability and abolished BD in CHF.
Article
Biochemistry & Molecular Biology
Fotini Koutroumpa, Christelle Monsempes, Sylvia Anton, Marie-Christine Francois, Nicolas Montagne, Emmanuelle Jacquin-Joly
Summary: In this study, the researchers used CRISPR-Cas9 technology to knock out the sex pheromone receptor in the noctuid moth Spodoptera littoralis. They found that the inactivation of the receptor specifically affected the response of corresponding antennal neurons, but did not impact the number of macroglomeruli in the antennal lobe. However, it did reduce the size of the macroglomerulus processing input from neurons tuned to the main pheromone component. This study provides the first evidence of the role of a moth pheromone receptor in macroglomerulus development and enhances our understanding of the various functions odorant receptors can have in insect neurodevelopment.
Review
Neurosciences
Jade Degrandmaison, Samuel Rochon-Hache, Jean-Luc Parent, Louis Gendron
Summary: The assessment of endogenous G protein-coupled receptors (GPCRs) is challenging due to their low expression levels, complex multi-pass transmembrane structure, and lack of specific antibodies. However, recent advances in genetic engineering have allowed the generation of unique mouse models, including knock-in models for opioid peptide receptors (OPr). These models have contributed significantly to our understanding of the in vivo mechanisms of OPr regulation and could have implications for the study of other GPCRs.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Neurosciences
Kevin Carvalho, Elodie Martin, Aurelia Ces, Nadege Sarrazin, Pauline Lagouge-Roussey, Caroline Nous, Leyna Boucherit, Ihsen Youssef, Annick Prigent, Emilie Faivre, Sabiha Eddarkaoui, Thibaut Gauvrit, Didier Vieau, Susana Boluda, Vincent Huin, Bertrand Fontaine, Luc Buee, Benoit Delatour, Patrick Dutar, Florian Sennlaub, Xavier Guillonneau, David Blum, Cecile Delarasse
Summary: The purinergic receptor P2X7 plays a crucial role in Alzheimer's disease and Tauopathies, with deletion of P2X7 having significant effects on inflammatory mediators and memory function in Tau pathology. P2X7 inhibitors may be ideal drugs for treating these neurodegenerative diseases.
PROGRESS IN NEUROBIOLOGY
(2021)
Review
Cell Biology
Tarik Issad, Hasanain Al-Mukh, Abdelouhab Bouaboud, Patrick Pagesy
Summary: O-GlcNAcylation is a crucial protein modification that regulates protein functions and cell signaling, and is associated with numerous physiological and pathological processes.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Biology
Yuki Ono, Kouki Kawakami, Gaku Nakamura, Satoru Ishida, Junken Aoki, Asuka Inoue
Summary: A HEK293 cell line lacking all G alpha i subunits is generated, allowing for the measurement of coupling between a GPCR and individual G alpha i subunits upon transient re-expression of a specific G alpha i subunit. Coupling selectivity across 11 GPCRs is analyzed by measuring ligand-induced inhibitory activity for cAMP accumulation. Results indicate that GPCRs fine-tune G alpha i signaling by exerting coupling preference at the G alpha i-subunit level.
COMMUNICATIONS BIOLOGY
(2023)
Article
Neurosciences
Una Greferath, Mario Huynh, Andrew Ian Jobling, Kirstan Anne Vessey, Gene Venables, Denver Surrao, Helen Christine O'Neill, Ioannis J. Limnios, Erica Lucy Fletcher
Summary: Retinitis pigmentosa is a group of inherited retinal degenerations characterized by gradual loss of photoreceptors, ultimately leading to irreversible vision loss. This study focused on analyzing the changes in glial, microglial, and photoreceptor cells in different retinal locations in RCS rats, revealing significant differences in photoreceptor loss between the dorsal and ventral retina. The findings suggest that breakdown of the outer limiting membrane may play a role in exacerbating photoreceptor loss in the ventral retina, highlighting the value of using the RCS rat model for sectorial retinitis pigmentosa.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Genetics & Heredity
Grace E. Lidgerwood, Anne Senabouth, Casey J. A. Smith-Anttila, Vikkitharan Gnanasambandapillai, Dominik C. Kaczorowski, Daniela Amann-Zalcenstein, Erica L. Fletcher, Shalin H. Naik, Alex W. Hewitt, Joseph E. Powell, Alice Pebay
Summary: The study characterizes the transcriptomic profiles of human pluripotent stem cell-derived retinal pigment epithelium (RPE) cells at different culture time points, revealing the maturation process of these cells in culture.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2021)
Review
Ophthalmology
Zhichao Wu, Erica L. Fletcher, Himeesh Kumar, Ursula Greferath, Robyn H. Guymer
Summary: Reticular pseudodrusen are distinct lesions in the subretinal space that have been increasingly recognized in association with age-related macular degeneration. Understanding their pathogenesis is crucial for understanding the processes driving vision loss in AMD.
PROGRESS IN RETINAL AND EYE RESEARCH
(2022)
Editorial Material
Genetics & Heredity
Samaneh Farashi, Zhichao Wu, Carla J. Abbott, Alice Pebay, Erica L. Fletcher, Robyn H. Guymer, Melanie Bahlo, Brendan R. E. Ansell
Summary: Reticular pseudodrusen (RPD) is a distinct phenotype associated with late-stage age-related macular degeneration (AMD), characterized by subretinal deposits. The genetic risk associations of RPD overlap with six established AMD-risk regions. Identifying the specific underlying genetic causes of RPD through adequate imaging methods can enhance our understanding of RPD pathophysiology.
TRENDS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Alice Brandli, Fay L. Khong, Roy C. K. Kong, Darren J. Kelly, Erica L. Fletcher
Summary: This study found the presence of fibrosis gene expression pathways in the laser induced CNV mouse model and suggested that anti-fibrotic treatments have the potential to reduce subretinal fibrosis in AMD.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Kirstan A. Vessey, Andrew Jobling, Mai X. Tran, Anna Y. Wang, Ursula Greferath, Erica L. Fletcher
Summary: Age-related macular degeneration (AMD) is a leading cause of vision loss, and recent evidence suggests that autophagy plays an important role in the progression of the disease. In this study, targeting autophagy was found to be effective in slowing dysfunction in a mouse model with features of early AMD. The treatments of metformin and trehalose showed potential in treating early AMD by enhancing autophagy pathways.
Article
Biochemistry & Molecular Biology
Candace Drysdale, Keunha Park, Kirstan A. Vessey, Xin Huang, Emily Caruso, Yihan Li, Joelyn Wong, James S. Wiley, Erica Fletcher, Robyn H. Guymer, Ben J. Gu
Summary: This study examined the membrane fluidity of peripheral blood leucocytes in patients with age-related macular degeneration (AMD) and in a mouse model lacking the P2X7 gene. The results showed decreased membrane fluidity in all types of leucocytes in late AMD patients. Pre-treatment with ATP increased membrane fluidity in monocytes and lymphocytes. P2X7 was found to mediate these ATP-driven increases in membrane fluidity, but without affecting pore formation or phagocytosis. The findings suggest a novel biological function of P2X7 in modulating membrane fluidity.
PURINERGIC SIGNALLING
(2022)
Review
Neurosciences
Josephine H. C. Wong, Jessica Y. W. Ma, Andrew I. I. Jobling, Alice Brandli, Ursula Greferath, Erica L. L. Fletcher, Kirstan A. A. Vessey
Summary: Age-related macular degeneration (AMD) is a major cause of irreversible vision loss in the older population, characterized by drusen accumulation and pigmentary abnormalities. The death of the retinal pigment epithelium (RPE) and photoreceptors in late AMD result in vision impairment. The RPE is crucial for retinal health and communicates with the retinal and systemic immune environment. Dysfunction of the RPE and aberrant immune cell recruitment contribute to the pathogenesis of AMD, involving chronic inflammation and disease progression.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Ophthalmology
Erica L. Fletcher, Michael A. Dixon, Samuel A. Mills, Andrew I. Jobling
Summary: Diabetic retinopathy is the most feared complication for those with diabetes. Recent studies have shown that a range of cellular changes occur in the retina from an early stage of diabetes, including a loss of vasoregulation in response to changes in neural activity. Retinal immune cells, microglia, play an important role in mediating vasoconstriction. These findings highlight the significance of early changes in vascular regulation to the progression of diabetic retinopathy.
CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2023)
Article
Genetics & Heredity
Dongmao Wang, Paul Trevillian, Stephen May, Peter Diakumis, Yanyan Wang, Deb Colville, Melanie Bahlo, Una Greferath, Erica Fletcher, Barbara Young, Heather G. Mack, Judy Savige
Summary: Scalp-Ear-Nipple syndrome, caused by pathogenic KCTD1 variants, is characterized by scalp defect, prominent ears, and rudimentary breasts. This study found further clinical associations in the eye and kidney.
OPHTHALMIC GENETICS
(2023)
Article
Anatomy & Morphology
Hallur Reynisson, Michael Kalloniatis, Erica L. Fletcher, Mohit N. Shivdasani, Lisa Nivison-Smith
Summary: A hallmark of photoreceptor degenerations is progressive, aberrant remodeling of the surviving retinal neurons and glia following photoreceptor loss. This study assessed the relationship between Muller cell dysfunction and retinal neuron subpopulations in late-stage retinal degeneration, finding that glia-neuronal alterations play a significant role. These findings highlight the importance of further research and intervention development in this field.
FRONTIERS IN NEUROANATOMY
(2023)
Article
Ophthalmology
Ursula Greferath, Erica Fletcher, Judy Savige, Heather G. Mack
Summary: Retinal drusen are uncommon in IgA nephropathy, but they resemble drusen found in age-related macular degeneration. The IgA-staining deposits in the drusen are likely related to systemic deposition of IgA. The nature of cystic spaces in the drusen is still unknown. Further research on the retinas of people with glomerulonephritis is recommended.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2024)
Article
Geriatrics & Gerontology
Jessica Y. W. Ma, Ursula Greferath, Josephine H. C. Wong, Linda J. Fothergill, Andrew I. Jobling, Kirstan A. Vessey, Erica L. Fletcher
Summary: This study investigated the changes in the retinal pigment epithelium (RPE) of C57BL/6J mice with age. The RPE structure was found to change, with increased cell size, loss of nuclei, and altered tight junctions in the peripheral retina. The study also revealed impairments in phagocytosis and autophagy processes in the aged RPE tissue, suggesting a contribution to RPE dysfunction and age-related macular degeneration (AMD) development.
NEUROBIOLOGY OF AGING
(2023)
Meeting Abstract
Ophthalmology
Quan Findlay, Ben Gu, Andrew Jobling, Erica Fletcher, Robyn Guymer
CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2022)
