Glutamate signalling in healthy and diseased bone

Bone relies on multiple extracellular signalling systems to maintain homeostasis of its normal structure and functions. The amino acid glutamate is a fundamental extracellular messenger molecule in many tissues, and is used in bone for both neural and non-neural signalling. This review focuses on the non-neural interactions, and examines the evolutionarily ancient glutamate signalling system in the context of its application to normal bone functioning and discusses recent findings on the role of glutamate signalling as they pertain to maintaining healthy bone structure. The underlying mechanisms of glutamate signalling and the many roles glutamate plays in modulating bone physiology are featured, including those involved in osteoclast and osteoblast differentiation and mature cell functions. Moreover, the relevance of glutamate signalling systems in diseases that affect bone, such as cancer and rheumatoid arthritis, is discussed, and will highlight how the glutamate system may be exploited as a viable therapeutic target. We will identify novel areas of research where knowledge of glutamate communication mechanisms may aid in our understanding of the complex nature of bone homeostasis. By uncovering the contributions of glutamate in maintaining healthy bone, the reader will discover how this complex molecular signalling system may advance our capacity to treat bone pathologies

Brain-charting autism and attention deficit hyperactivity disorder reveals distinct and overlapping neurobiology.

BACKGROUND: Autism and attention deficit hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology that is still poorly understood. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together, and sex differences are often overlooked. Population modelling, often referred to as normative modelling, provides a unified framework for studying age-specific and sex-specific divergences in brain development. METHODS: Here we used population modelling and a large, multi-site neuroimaging dataset (N = 4255 after quality control) to characterise cortical anatomy associated with autism and ADHD, benchmarked against models of average brain development based on a sample of over 75,000 individuals. We also examined sex and age differences, relationship with autistic traits, and explored the co-occurrence of autism and ADHD (autism+ADHD). RESULTS: We observed robust neuroanatomical signatures of both autism and ADHD. Overall, autistic individuals showed greater cortical thickness and volume, that was localised to the superior temporal cortex, whereas individuals with ADHD showed more global increases in cortical thickness, but lower cortical volume and surface area across much of the cortex. The autism+ADHD group displayed a unique pattern of widespread increases in cortical thickness, and certain decreases in surface area. We also found evidence that sex modulates the neuroanatomy of autism but not ADHD, and an age-by-diagnosis interaction for ADHD only. CONCLUSIONS: These results indicate distinct cortical differences in autism and ADHD that are differentially impacted by age, sex, and potentially unique patterns related to their co-occurrence

Brain-charting autism and attention deficit hyperactivity disorder reveals distinct and overlapping neurobiology

Background Autism and attention deficit hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology that is still poorly understood. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together, and sex differences are often overlooked. Population modelling, often referred to as normative modelling, provides a unified framework for studying age-specific and sex-specific divergences in brain development. Methods Here we used population modelling and a large, multi-site neuroimaging dataset (N = 4255 after quality control) to characterise cortical anatomy associated with autism and ADHD, benchmarked against models of average brain development based on a sample of over 75,000 individuals. We also examined sex and age differences, relationship with autistic traits, and explored the co-occurrence of autism and ADHD (autism+ADHD). Results We observed robust neuroanatomical signatures of both autism and ADHD. Overall, autistic individuals showed greater cortical thickness and volume, that was localised to the superior temporal cortex, whereas individuals with ADHD showed more global increases in cortical thickness, but lower cortical volume and surface area across much of the cortex. The autism+ADHD group displayed a unique pattern of widespread increases in cortical thickness, and certain decreases in surface area. We also found evidence that sex modulates the neuroanatomy of autism but not ADHD, and an age-by-diagnosis interaction for ADHD only. Conclusions These results indicate distinct cortical differences in autism and ADHD that are differentially impacted by age, sex, and potentially unique patterns related to their co-occurrence

Braincharts for the human lifespan

Over the past 25 years, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, there are no reference standards against which to anchor measures of individual differences in brain morphology, in contrast to growth charts for traits such as height and weight. Here, we built an interactive online resource (www.brainchart.io) to quantify individual differences in brain structure from any current or future magnetic resonance imaging (MRI) study, against models of expected age-related trends. With the goal of basing these on the largest and most inclusive dataset, we aggregated MRI data spanning 115 days post-conception through 100 postnatal years, totaling 122,123 scans from 100,071 individuals in over 100 studies across 6 continents. When quantified as centile scores relative to the reference models, individual differences show high validity with non-MRI brain growth estimates and high stability across longitudinal assessment. Centile scores helped identify previously unreported brain developmental milestones and demonstrated increased genetic heritability compared to non-centiled MRI phenotypes. Crucially for the study of brain disorders, centile scores provide a standardised and interpretable measure of deviation that reveals new patterns of neuroanatomical differences across neurological and psychiatric disorders emerging during development and ageing. In sum, brain charts for the human lifespan are an essential first step towards robust, standardised quantification of individual variation and for characterizing deviation from age-related trends. Our global collaborative study

A longitudinal resource for population neuroscience of school-age children and adolescents in China

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community (https://ccnp.scidb.cn) at the Science Data Bank

COS Ambassadors

A collection of materials and resources for COS ambassadors