Forebrain development is characterized by highly synchronized cellular processes, which, if perturbed, can cause disease. To chart the regulatory activity underlying these events, we generated a map of accessible chromatin in human three-dimensional forebrain organoids. To capture corticogenesis, we sampled glial and neuronal lineages from dorsal or ventral forebrain organoids over 20 months in vitro. Active chromatin regions identified in human primary brain tissue were observed in organoids at different developmental stages. We used this resource to map genetic risk for disease and to explore evolutionary conservation. Moreover, we integrated chromatin accessibility with transcriptomics to identify putative enhancer-gene linkages and transcription factors that regulate human corticogenesis. Overall, this platform brings insights into gene-regulatory dynamics at previously inaccessible stages of human forebrain development, including signatures of neuropsychiatric disorders.
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http://dx.doi.org/10.1126/science.aay1645 | DOI Listing |
J Integr Neurosci
January 2025
Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 637000 Nanchong, Sichuan, China.
Background: Volume alterations in the parietal subregion have received less attention in Alzheimer's disease (AD), and their role in predicting conversion of mild cognitive impairment (MCI) to AD and cognitively normal (CN) to MCI remains unclear. In this study, we aimed to assess the volumetric variation of the parietal subregion at different cognitive stages in AD and to determine the role of parietal subregions in CN and MCI conversion.
Methods: We included 662 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, including 228 CN, 221 early MCI (EMCI), 112 late MCI (LMCI), and 101 AD participants.
Nutrients
January 2025
School of Pharmacy, Shaoyang University, Shaoyang 422000, China.
Depression, a serious mental illness, is characterized by high risk, high incidence, persistence, and tendency to relapse, posing a significant burden on global health. The connection between depression and gut microbiota is an emerging field of study in psychiatry and neuroscience. Understanding the gut-brain axis is pivotal for understanding the pathogenesis and treatment of depression.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia.
Traumatic brain injury (TBI) is one of the primary causes of mortality and disability, with arterial blood pressure being an important factor in the clinical management of TBI. Spontaneously hypertensive rats (SHRs), widely used as a model of essential hypertension and vascular dementia, demonstrate dysfunction of the hypothalamic-pituitary-adrenal axis, which may contribute to glucocorticoid-mediated hippocampal damage. The aim of this study was to assess acute post-TBI seizures, delayed mortality, and hippocampal pathology in SHRs and normotensive Sprague Dawley rats (SDRs).
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Laboratory of Neuroendocrinology and In Situ Hybridization, Department of Anatomy, Histology and Embryology, Semmelweis University, H1094 Budapest, Hungary.
The ability to reproduce depends on metabolic status. In rodents, the ventral premammillary nucleus (PMv) integrates metabolic and reproductive signals. While leptin (adiposity-related) signaling in the PMv is critical for female fertility, male reproductive functions are strongly influenced by glucose homeostasis.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Neuroscience and Mental Health Innovation Institute, Cardiff University, Hadyn Ellis Building, Cardiff CF24 4HQ, UK.
Deletion and duplication in the human 16p11.2 chromosomal region are closely linked to neurodevelopmental disorders, specifically autism spectrum disorder. Data from neuroimaging studies suggest white matter microstructure aberrations across these conditions.
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