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)
Article
Psychiatry
Evelyn B. N. Friedel, Hannah-Tabea Hahn, Simon Maier, Sebastian Kuechlin, Michael Reich, Kimon Runge, Michael Bach, Sven P. Heinrich, Juergen Kornmeier, Dominique Endres, Dieter Ebert, Katharina Domschke, Ludger Tebartz van Elst, Kathrin Nickel
Summary: This study explores the differences in both structural and functional retina between patients with paranoid schizophrenia and healthy controls. The findings highlight the importance of comprehensive assessment of the visual system in patients with schizophrenia, and the need for further investigation into the effects of antipsychotic medication, duration of illness, and other factors.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Medicine, General & Internal
Aoife Murray, Gillian Gough, Ana Cindric, Frano Vuckovic, David Koschut, Vincenzo Borelli, Drazen J. Petrovic, Ana Bekavac, Ante Plecas, Valentina Hribljan, Reinhard Brunmeir, Julija Juric, Maja Pucic-Bakovic, Anita Slana, Helena Deris, Azra Frkatovic, Jurgen Groet, Niamh L. O'Brien, Hong Yu Chen, Yee Jie Yeap, Frederic Delom, Steven Havlicek, Luke Gammon, Sarah Hamburg, Carla Startin, Hana D'Souza, Dinko Mitrecic, Mijana Kero, Ljubica Odak, Bozo Kruslin, Zeljka Krsnik, Ivica Kostovic, Jia Nee Foo, Yuin-Han Loh, Norris Ray Dunn, Susana de la Luna, Tim Spector, Ingeborg Barisic, Michael S. C. Thomas, Andre Strydom, Claudio Franceschi, Gordan Lauc, Jasminka Kristic, Ivan Alic, Dean Nizetic
Summary: This study found that individuals with Down syndrome have a biological age that is, on average, 18.4-19.1 years older than their chronological age, and this difference remains consistent throughout their lifespan. The overexpression of chromosome 21 genes in the blood of Down syndrome patients was found to be associated with DNA damage and cellular aging. Through gene editing and pharmacological interventions, the researchers demonstrated that reducing the expression of the DYRK1A gene can alleviate these effects.
Article
Biochemistry & Molecular Biology
Hao Liu, Rene N. M. Caballero-Floran, Ty Hergenreder, Tao Yang, Jacob W. Hull, Geng Pan, Ruonan Li, Macy Veling, Lori G. Isom, Kenneth M. Kwan, Z. Josh Huang, Peter Fuerst, Paul Jenkins, Bing Ye
Summary: Down syndrome is caused by the trisomy of human chromosome 21. This study found that DSCAM levels regulate GABAergic synapse formation on pyramidal neurons, and overexpression of DSCAM leads to excessive GABAergic input and increased inhibition. Conversely, loss of DSCAM impairs GABAergic synapse development and function.
Article
Plant Sciences
Miri Choi, Ae-kyeong Kim, Youngwook Ham, Joo-Youn Lee, Daeyong Kim, Ansook Yang, Min Ju Jo, Eunyoung Yoon, Jung-Nyoung Heo, Sang-Bae Han, Min-Hyo Ki, Kyu-Sun Lee, Sungchan Cho
Summary: Aristolactam BIII, a natural product derived from herbal plants, was identified as a novel DYRK1A inhibitor with therapeutic potential for DS-related pathological conditions.
Review
Cell Biology
Bani Bandana Ganguly, Nitin N. Kadam
Summary: Gene triplication on human chromosome 21 is responsible for Down syndrome (DS) phenotypes, causing dosage imbalance in nuclear genes and mitochondrial DNA (mtDNA), affecting energy production, respiration, and redox homeostasis in cells. Cell tissues from DS patients and DS mouse models show elevated mtDNA numbers but reduced content due to increased fission process, impacting oxidative phosphorylation and cellular protection from toxic environments. The complex interplay between nuclear and mitochondrial genomes contributes to mitochondrial dysfunction, affecting organ function and promoting neurodegenerative diseases and cardiac complexities in individuals with DS.
Article
Developmental Biology
Yushi Redhead, Dorota Gibbins, Eva Lana-Elola, Sheona Watson-Scales, Lisa Dobson, Matthias Krause, Karen J. Liu, Elizabeth M. C. Fisher, Jeremy B. A. Green, Victor L. J. Tybulewicz
Summary: Down syndrome (DS) is a common human chromosomal abnormality that leads to various phenotypic features, including craniofacial dysmorphology. Through analysis of a DS mouse model and genetic mapping, it was found that four regions on mouse chromosome 16, which correspond to Hsa21 in humans, contain dosage-sensitive genes that contribute to DS craniofacial abnormalities, with Dyrk1a identified as one of the causative genes. The study revealed that the earliest and most severe defects in the DS mouse skulls occur in bones of neural crest origin, and that abnormal mineralization of the skull base synchondroses is present. Additionally, increased dosage of Dyrk1a was found to result in decreased proliferation of neural crest cells and a reduction in size and cellularity of the frontal bone primordia.
Article
Chemistry, Medicinal
Wenche Stensen, Ulli Rothweiler, Richard Alan Engh, Melissa R. Stasko, Ilya Bederman, Alberto C. S. Costa, Anders Fugelli, John S. Mjoen Svendsen
Summary: Down syndrome is a complex genetic disorder with substantial physical, cognitive, and behavioral challenges. While treatment options for physical co-morbidities have improved, cognitive deficits in individuals with DS cannot be addressed pharmacologically, and all individuals with DS develop early onset Alzheimer's disease pathology by the age of 40. The study introduces a novel inhibitor for the protein kinase DYRK1A, which is a key controlling kinase associated with DS.
Article
Neurosciences
Maria Elisa Serrano, Eugene Kim, Bernard Siow, Da Ma, Loreto Rojo, Camilla Simmons, Darryl Hayward, Dorota Gibbins, Nisha Singh, Andre Strydom, Elizabeth M. C. Fisher, Victor L. J. Tybulewicz, Diana Cash
Summary: This study investigated the impact of Down syndrome-related genetic abnormalities on the brain phenotype using a DS mouse model. The findings revealed neuroanatomical and biochemical alterations in the DS brains, including changes in brain surface area, shape, volume, and regional volume. Metabolite analysis showed an imbalance in the excitation/inhibition ratio, and histological analysis revealed changes in neuron and glial cell populations. These findings contribute to a better understanding of the connection between chromosome 21 trisomy and the resulting phenotype.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Nutrition & Dietetics
Carmen Martinez-Cue, Renata Bartesaghi
Summary: Down syndrome (DS) is a genetic disorder caused by the triplication of chromosome 21, resulting in intellectual disability starting in utero and continuing through infancy, with associated impairments in neurogenesis and connectivity that may lead to early-onset Alzheimer's disease. Current research focuses on using DS mouse models to discover potential pharmacotherapies, with fatty acids emerging as a promising treatment option for DS-related cognitive deficits and neurodevelopmental impairments. This suggests a need for further exploration of the potential benefits of fatty acids for individuals with DS.
Article
Behavioral Sciences
Yi Shao, Lin Yang, Pei-Wen Zhu, Ting Su, Xue-Zhi Zhou, Biao Li, Wen-Qing Shi, Qi Lin, You-Lan Min, Qing Yuan, Lei Ye, Qiong Zhou
Summary: Middle-age patients with retinal detachment exhibit changes in local functional connectivity density (lFCD) and long-range functional connectivity density (longFCD) in specific brain areas. Increased lFCD values were observed in the right inferior temporal gyrus, while increased longFCD values were observed in various brain regions. Decreased lFCD and longFCD values were also found in certain brain regions.ROC curve analysis showed excellent accuracy in distinguishing middle-age RD patients from normal controls.
BRAIN AND BEHAVIOR
(2021)
Article
Neurosciences
Mireia Ortega, Ilario De Toma, Alvaro Fernandez-Blanco, Anna Calderon, Lucia Barahona, Ramon Trullas, Eduard Sabido, Mara Dierssen
Summary: This study found that Dyrk1A overexpression affects oxidative phosphorylation and mitochondrial function in the cerebellum, and the EGCG in green tea extract can partially restore these changes.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Review
Endocrinology & Metabolism
Eleni Papakokkinou, Oskar Ragnarsson
Summary: Cognitive impairment and affective disorders are common in patients with Cushing's syndrome, and the deleterious effects of cortisol excess on the brain can lead to memory problems, concentration difficulties, and impaired executive function. Neuroimaging studies have shown structural alterations in brain regions such as the hippocampus, amygdala, and prefrontal cortex. Functional magnetic resonance imaging studies have also revealed alterations in brain areas and networks important for cognitive and emotional processing. Longitudinal studies are still needed to determine whether these effects are reversible.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Genetics & Heredity
Jared R. Thomas, Kourtney Sloan, Kelsey Cave, Joseph M. Wallace, Randall J. Roper
Summary: Trisomy 21 causes skeletal abnormalities in individuals with Down syndrome, with bone density deficits showing sexual dimorphism. Reduced osteoblast function may contribute to these anomalies.
Article
Genetics & Heredity
Xiuxiu Jin, Jingyang Liu, Weiping Wang, Jiangfeng Li, Guangming Liu, Ruiqi Qiu, Mingzhu Yang, Meng Liu, Lin Yang, Xiaofeng Du, Bo Lei
Summary: This study analyzed the molecular changes of retinal pigment epithelium (RPE) cells during aging through quantitative proteomic analysis. The findings suggest that protein ubiquitination related to RNF123 and RNF149 plays a crucial role in protecting RPE cells from oxidative damage.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2022)
Article
Clinical Neurology
David J. Whiteside, Maura Malpetti, P. Simon Jones, Boyd C. P. Ghosh, Ian Coyle-Gilchrist, John C. van Swieten, Harro Seelaar, Lize Jiskoot, Barbara Borroni, Raquel Sanchez-Valle, Fermin Moreno, Robert Laforce, Caroline Graff, Matthis Synofzik, Daniela Galimberti, Mario Masellis, Maria Carmela Tartaglia, Elizabeth Finger, Rik Vandenberghe, Alexandre de Mendonca, Fabrizio Tagliavini, Chris R. Butler, Isabel Santana, Isabelle Le Ber, Alexander Gerhard, Simon Ducharme, Johannes Levin, Adrian Danek, Markus Otto, Sandro Sorbi, Florence Pasquier, Arabella Bouzigues, Lucy L. Russell, Jonathan D. Rohrer, James B. Rowe, Timothy Rittman
Summary: This study investigated the role of changes in functional networks in predicting cognitive decline and conversion to symptomatic disease in familial frontotemporal dementia (FTD). The study found a characteristic pattern of dynamic network changes in FTD, which were correlated with neuropsychological impairment. Among presymptomatic mutation carriers, this pattern of network dynamics was more prominent in those who later converted to the symptomatic phase. Baseline network dynamic changes predicted future cognitive decline in symptomatic participants and older presymptomatic participants.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Jose Bourbon-Teles, Lilia Jorge, Nadia Canario, Ricardo Martins, Isabel Santana, Miguel Castelo-Branco
Summary: Using two imaging modalities, this study investigated the associations between cortical amyloid-beta burden, fornix microstructural changes, and cognitive deficits in early Alzheimer's disease. Results showed impairments in cognitive performance, reductions in fornix fractional anisotropy, and increases in cortical amyloid-beta burden in patients. Positive associations were found between fornix fractional anisotropy and performance for all visual object categories, while a negative association was observed between cortical amyloid-beta burden and performance for object categories. Overall cognition was positively associated with fornix fractional anisotropy, but not with cortical amyloid-beta burden.
Article
Cell Biology
Anna Sires, Mateo Pazo-Gonzalez, Joaquin Lopez-Soriano, Ana Mendez, Enrique J. J. de la Rosa, Pedro de la Villa, Joan X. X. Comella, Catalina Hernandez-Sanchez, Montse Sole
Summary: The short and long isoforms of FAIM play important roles in the central nervous system and are highly expressed in the retina. Knockout of Faim gene in mice leads to functional loss of rod photoreceptor and ganglion cells, as well as a delay in dark adaptation. Abnormal redistribution of Arrestin-1 and its ubiquitination may contribute to the impairments observed in Faim knockout mice.
Review
Biochemistry & Molecular Biology
Francisco M. Ribeiro, Miguel Castelo-Branco, Joana Goncalves, Joao Martins
Summary: Assessing the molecular mechanism of synaptic plasticity in the cortex is crucial for identifying potential targets in conditions marked by defective plasticity. In this review, two major plasticity protocols (ocular-dominance and cross-modal) in rodents are discussed, focusing on the molecular signaling pathways involved. Additionally, the contribution of different populations of inhibitory and excitatory neurons at different time points is highlighted. The potentially disrupted molecular and circuit alterations in various neurodevelopmental disorders are also explored, and new plasticity paradigms, such as stimulus-selective response potentiation, are presented as potential tools to repair plasticity defects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Clinical Neurology
Sara Bernardo-Castro, Joao Andre Sousa, Emanuel Martins, Helena Donato, Cesar Nunes, Otilia C. d'Almeida, Miguel Castelo-Branco, Antero Abrunhosa, Lino Ferreira, Joao Sargento-Freitas
Summary: This study aims to assess the evolution of blood-brain barrier permeability (BBBp) throughout different phases of ischemic stroke and its impact on patient outcomes. The results showed that BBBp consistently increases after stroke, peaking in the acute phase. The degree of BBBp influences patient outcomes depending on the stroke phase, highlighting the clinical relevance of BBBp dynamics in stroke care.
INTERNATIONAL JOURNAL OF STROKE
(2023)
Article
Biochemistry & Molecular Biology
Beatriz Caramelo, Tamaeh Monteiro-Alfredo, Joao Martins, Jose Sereno, Joao Castelhano, Bruno Manadas, Miguel Castelo-Branco, Paulo Matafome
Summary: Functional MRI (fMRI) with H-1-MRS was used to study the neurometabolic changes in animal models of obesity and type 2 diabetes. Rats on a high-fat diet showed elevated levels of NAAG and GSH in the hippocampus, whereas diabetic rats showed elevated levels of taurine and GABA(A)R in the visual cortex. These findings suggest different mechanisms and responses to metabolic and vascular insults in different brain regions.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Medicine, General & Internal
Diogo Pinto, Ricardo Martins, Antonio Macedo, Miguel Castelo Branco, Joao Valente Duarte, Nuno Madeira
Summary: This study compared brain asymmetry in patients with schizophrenia (SCZ), bipolar disorder (BPD), and healthy controls. Significant differences in gray matter asymmetry were found between SCZ patients and BPD patients, SCZ patients and healthy controls, and BPD patients and healthy controls.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Neurosciences
Joana Crisostomo, Joao V. Duarte, Nadia Canario, Carolina Moreno, Leonor Gomes, Miguel Castelo-Branco
Summary: Type 2 diabetes affects brain structure, specifically cortical gyrification. This study investigated the impact of variations in glycemic profile over time on gyrification in individuals with type 2 diabetes. The findings suggest that glycemic control might influence gyrification in this metabolic disease.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2023)
Article
Behavioral Sciences
Carla Soares, Gerardo Gonzalo, Joao Castelhano, Miguel Castelo-Branco
Summary: The Default Mode Network (DMN) and the Theory of Mind (ToM) networks are important in understanding self-neurocognition. While the DMN is associated with introspection, the ToM is involved in perspective-taking. However, there is no research on the overlap between DMN and ToM in relation to causal effects induced by psychedelics, and their precise relationship remains unknown. Psychedelics alter self-perception and modulate these networks, which can provide insights into this relationship.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Article
Business
Ricardo Cayolla, Rui Biscaia, Roy F. Baumeister, Marc Fetscherin, Sonia Brito-Costa, Isabel C. Duarte, Miguel Castelo-Branco
Summary: This neuroimaging study examines the brain activation patterns of sport fans in response to team stimuli. The study aims to identify the brain structures involved in positive, neutral, and negative events, as well as to determine which events elicit stronger limbic network activation. The results reveal activation of the cingulate gyrus, hippocampus, parahippocampus, and ventral tegmental area, indicating the involvement of the limbic and reward systems. Positive videos have a greater impact on emotional regulation and memory areas compared to neutral and negative videos. The study highlights the neural basis of fan reactions to team-related stimuli and emphasizes the importance of understanding the influence of different types of content on emotional and memory processes.
JOURNAL OF CONSUMER BEHAVIOUR
(2023)
Article
Clinical Neurology
Marta Lapo Pais, Lilia Jorge, Ricardo Martins, Nadia Canario, Ana Carolina Xavier, Rui Bernardes, Antero Abrunhosa, Isabel Santana, Miguel Castelo-Branco
Summary: Alzheimer's disease is the most common form of dementia, characterized by the accumulation of amyloid plaques and neurofibrillary tangles. This study explores the use of textural parameters as an alternative to kinetic models for assessing the state and progression of Alzheimer's disease in (R)-[C-11]PK11195 PET images. The results show that textural parameters can achieve similar classification accuracy to kinetic analysis in the evaluation of Alzheimer's disease.
BRAIN COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Mariana Lapo Pais, Joao Martins, Miguel Castelo-Branco, Joana Goncalves
Summary: Tryptophan is an essential amino acid that plays a role in neuropsychiatric diseases. Women have a higher susceptibility to serotonin alterations due to changes in tryptophan levels, leading to a female sex bias in neuropsychiatric diseases. Further research is needed on the impact of diet and sex steroids on tryptophan metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neuroimaging
Helena Jorge, Isabel C. Duarte, Miguel Melo, Ana Paula Relvas, Miguel Castelo-Branco
Summary: Neuroimaging studies in patients with Type 1 Diabetes Mellitus reveal that health-consequent decision-making is associated with reward-related neural regions, and the trajectory of blood sugar control is correlated with neural risk processing in the saliency network.
BRAIN IMAGING AND BEHAVIOR
(2023)
Review
Radiology, Nuclear Medicine & Medical Imaging
Maria Caranova, Julia F. Soares, Sonia Batista, Miguel Castelo-Branco, Joao Valente Duarte
Summary: Multiple sclerosis (MS) is a common white matter disease characterized by demyelination and inflammation. Conventional structural MRI lacks sensitivity and specificity in detecting damage to normal appearing tissues. Diffusion-weighted MRI models such as DTI and NODDI allow for the detection of microstructural abnormalities in MS, particularly in normal appearing white matter (NAWM). Comparing the two methods, NODDI shows higher sensitivity and specificity. The use of advanced diffusion models can provide valuable biomarkers for understanding treatment efficacy and disease progression in clinical practice.
MAGNETIC RESONANCE IMAGING
(2023)
Article
Cardiac & Cardiovascular Systems
Luis Leite, Gustavo Campos, Rodolfo Silva, Elisabete Jorge, Manuel Oliveira-Santos, Andreia Gomes, Lino Goncalves, Miguel Castelo-Branco, Antero Abrunhosa, Maria Joao Ferreira
Summary: This study analyzed the association between ischemia and hibernating myocardium evaluated by cardiac PET-CT and the angiographic characterization of collateral circulation in chronic total occlusion (CTO) patients. The results showed a poor association between collateral assessment by angiography and the ischemic burden and hibernation state of CTO territories. Myocardial viability was still present in most CTO with angiographic poorly developed collaterals.
INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING
(2023)