The powerful regulation of bone mass exerted by the brain suggests the existence of bone-derived signals modulating this regulation or other functions of the brain. We show here that the osteoblast-derived hormone osteocalcin crosses the blood-brain barrier, binds to neurons of the brainstem, midbrain, and hippocampus, enhances the synthesis of monoamine neurotransmitters, inhibits GABA synthesis, prevents anxiety and depression, and favors learning and memory independently of its metabolic functions. In addition to these postnatal functions, maternal osteocalcin crosses the placenta during pregnancy and prevents neuronal apoptosis before embryos synthesize this hormone. As a result, the severity of the neuroanatomical defects and learning and memory deficits of Osteocalcin(-/-) mice is determined by the maternal genotype, and delivering osteocalcin to pregnant Osteocalcin(-/-) mothers rescues these abnormalities in their Osteocalcin(-/-) progeny. This study reveals that the skeleton via osteocalcin influences cognition and contributes to the maternal influence on fetal brain development.
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http://dx.doi.org/10.1016/j.cell.2013.08.042 | DOI Listing |
CNS Neurosci Ther
January 2025
Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
Objectives: Parkinson's disease (PD) is characterized by olfactory dysfunction (OD) and cognitive deficits at its early stages, yet the link between OD and cognitive deficits is also not well-understood. This study aims to examine the changes in the olfactory network associated with OD and their relationship with cognitive function in de novo PD patients.
Methods: A total of 116 drug-naïve PD patients and 51 healthy controls (HCs) were recruited for this study.
Am J Cancer Res
December 2024
Department of Oncology, Anhui Medical University Hefei 230000, Anhui, China.
Radioactive brain injury, a severe complication ensuing from radiotherapy for head and neck malignancies, frequently manifests as cognitive impairment and substantially diminishes patients' quality of life. Despite its profound impact, the pathogenesis of this condition remains inadequately elucidated, and efficacious treatments are notably absent in clinical practice. Consequently, contemporary interventions predominantly focus on symptom alleviation rather than achieving a radical cure or reversing the injury process.
View Article and Find Full Text PDFThe central nervous system (CNS) parenchyma has conventionally been believed to lack lymphatic vasculature, likely due to a non-permissive microenvironment that hinders the formation and growth of lymphatic endothelial cells (LECs). Recent findings of ectopic expression of LEC markers including Prospero Homeobox 1 (PROX1), a master regulator of lymphatic differentiation, and the vascular permeability marker Plasmalemma Vesicle Associated Protein (PLVAP), in certain glioblastoma and brain arteriovenous malformations (AVMs), has prompted investigation into their roles in cerebrovascular malformations, tumor environments, and blood-brain barrier (BBB) abnormalities. To explore the relationship between ectopic LEC properties and BBB disruption, we utilized endothelial cell-specific overexpression mutants.
View Article and Find Full Text PDFThe biological mechanisms underlying women's increased Alzheimer's disease (AD) prevalence remain undefined. Previous case/control studies have identified sex-biased molecular pathways, but sex-specific relationships between gene expression and AD endophenotypes, particularly sex chromosomes, are underexplored. With bulk transcriptomic data across 3 brain regions from 767 decedents, we investigated sex-specific associations between gene expression and post-mortem β-amyloid and tau as well as antemortem longitudinal cognition.
View Article and Find Full Text PDFUnlabelled: The rat offers a uniquely valuable animal model in neuroscience, but we currently lack an individual-level understanding of the in vivo rat brain network. Here, leveraging longitudinal measures of cortical magnetization transfer ratio (MTR) from in vivo neuroimaging between postnatal days 20 (weanling) and 290 (mid-adulthood), we design and implement a computational pipeline that captures the network of structural similarity (MIND, morphometric inverse divergence) between each of 53 distinct cortical areas. We first characterized the normative development of the network in a cohort of rats undergoing typical development (N=47), and then contrasted these findings with a cohort exposed to early life stress (ELS, N=40).
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