The blood-brain barrier (BBB) is a unique set of properties of the brain vasculature which severely restrict its permeability to proteins and small molecules. Classic chick-quail chimera studies have shown that these properties are not intrinsic to the brain vasculature but rather are induced by surrounding neural tissue. Here, we identify Spock1 as a candidate neuronal signal for regulating BBB permeability in zebrafish and mice. Mosaic genetic analysis shows that neuronally expressed Spock1 is cell non-autonomously required for a functional BBB. Leakage in spock1 mutants is associated with altered extracellular matrix (ECM), increased endothelial transcytosis, and altered pericyte-endothelial interactions. Furthermore, a single dose of recombinant SPOCK1 partially restores BBB function in spock1 mutants by quenching gelatinase activity and restoring vascular expression of BBB genes including mcamb. These analyses support a model in which neuronally secreted Spock1 initiates BBB properties by altering the ECM, thereby regulating pericyte-endothelial interactions and downstream vascular gene expression.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525910 | PMC |
| http://dx.doi.org/10.1016/j.devcel.2023.06.005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The transcriptional response of cortical neurons to concussion reveals divergent fates after injury.
Nat Commun
January 2025
Unit on the Development of Neurodegeneration, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Traumatic brain injury (TBI) is a risk factor for neurodegeneration, however little is known about how this kind of injury alters neuron subtypes. In this study, we follow neuronal populations over time after a single mild TBI (mTBI) to assess long ranging consequences of injury at the level of single, transcriptionally defined neuronal classes. We find that the stress-responsive Activating Transcription Factor 3 (ATF3) defines a population of cortical neurons after mTBI.
View Article and Find Full Text PDFGlutamate-mediated antidepressant effects of Jieyu I Formula via modulation of PFC-LHb circuitry in lipopolysaccharide-induced depression model.
J Ethnopharmacol
January 2025
State Key Laboratory of Traditional Chinese Medicine Syndrome, International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, 519031, China. Electronic address:
Ethnopharmacological Relevance: Jieyu I Formula (JY-I) is an improved version of the classic formula "Sini San" documented in the books Shanghan Lun, which is known for regulating the liver and treating depression. However, the disturbance of neuronal signal transmission in the neural circuit of the brain is closely related to the occurrence of depression, yet its neural mechanism is still unclear.
Aim Of The Study: This study aimed to observe the antidepressant effect of JY-I on depressed mice induced by lipopolysaccharide and its underlying central nervous system mechanisms, focusing on the prefrontal cortex (PFC) to lateral habenular nucleus (LHb) neural circuit in the depressed mice model.
Liposomes-Loaded miR-9-5p Alleviated Hypoxia-Ischemia-Induced Mitochondrial Oxidative Stress by Targeting ZBTB20 to Inhibiting Nrf2/Keap1 Interaction in Neonatal Mice.
Antioxid Redox Signal
January 2025
Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.
Hypoxia ischemia (HI) is a leading cause of cerebral palsy and long-term neurological sequelae in infants. Given that mitochondrial dysfunction in neurons contributes to HI brain damage, this study aimed to investigate the regulatory role of miR-9-5p in mitochondrial function following HI injury. Overexpression of miR-9-5p in HI mice or HO-exposed PC12 cells suppressed neuronal injury, associated with increased mitochondrial copy number, normalizing mitochondrial membrane potential, improved nuclear factor-erythroid factor 2-related factor 2 (Nrf2) activation, and downregulation of Keap1.
View Article and Find Full Text PDFRecording and manipulating neuronal ensembles that underlie cognition and behavior is challenging. FLARE is a light- and calcium-gated transcriptional reporting system for labeling activated neurons on the order of minutes. However, FLARE is limited by its sensitivity to prolonged neuronal activities.
View Article and Find Full Text PDFBackground: Tau protein accumulation is closely linked to synaptic and neuronal loss in Alzheimer's disease (AD), resulting in progressive cognitive decline. Although tau-PET imaging is a direct biomarker of tau pathology, it is costly, carries radiation risks, and is not widely accessible. Resting-state functional MRI (rs-fMRI) complexity-an entropy-based measure of BOLD signal variation-has been proposed as a non-invasive surrogate biomarker of early neuronal dysfunction associated with tau pathology.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!