Bone morphogenetic protein (BMP) signaling has been shown to be intimately associated with adult neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ). Adult neurogenesis declines in aging rodents and primates. However, the role of BMP signaling in the age-related neurogenesis decline remains elusive and the effect of BMP4 on adult SVZ neurogenesis remains controversial. Here, the expression of BMP4 and its canonical effector phosphorylated-Smad1/5/8 (p-Smad1/5/8) in the murine SVZ and SGZ were found to be increased markedly with age. We identified Id3 as a major target of BMP4 in neuronal stem cells (NSCs) of both neurogenic regions, which exhibited a similar increase during aging. Intracerebroventricular infusion of BMP4 activated Smad1/5/8 phosphorylation and upregulated Id3 expression, which further restrained NeuroD1, leading to attenuated neurogenesis in both neurogenic regions and defective differentiation in the SGZ. Conversely, noggin, a potent inhibitor of BMP4, demonstrated opposing effects. In support of this, BMP4 treatment or lentiviral overexpression of Id3 resulted in decreased NeuroD1 protein levels in NSCs of both neurogenic regions and significantly inhibited neurogenesis. Thus, our findings revealed that the increased BMP4 signaling with age inhibited adult neurogenesis in both SVZ and SGZ, which may be attributed at least in part, to the changes in the Id3-NeuroD1 axis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138880 | PMC |
| http://dx.doi.org/10.3390/biomedicines10051147 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
LONG-LASTING EFFECTS OF EARLY POSTNATAL DYSFUNCTION OF THE BRAIN MUSCARINIC CHOLINERGIC SYSTEM ON LEARNING AND MEMORY AND ADULT HIPPOCAMPAL NEUROGENESIS.
Georgian Med News
November 2024
Lab. Neurobiology of Sleep-Wakefulness Cycle, Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia.
Aim: The present investigation aimed to explore in rats the early postnatal dysfunction of the brain muscarinic cholinergic system (EPDMChS) during the most vulnerable period of postnatal development, as the possible main factor for changes in adult hippocampal neurogenesis and disorders in hippocampus-dependent spatial learning and memory.
Methods: White inbred rats (n=15 in each group) were used. EPDMCHS was produced by a new method, which includes early postnatal blocking of M1-M5 muscarinic acetylcholine receptors in the rat pups, using subcutaneous injection of Scopolamine during postnatal days 7-28.
Traumatic Brain Injury Promotes Neurogenesis and Oligodendrogenesis in Subcortical Brain Regions of Mice.
Cells
January 2025
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Science, Moscow 117485, Russia.
Traumatic brain injury (TBI) is one of the major causes of severe neurological disorders and long-term dysfunction in the nervous system. Besides inducing neurodegeneration, TBI alters stem cell activity and neurogenesis within primary neurogenic niches. However, the fate of dividing cells in other brain regions remains unclear despite offering potential targets for therapeutic intervention.
View Article and Find Full Text PDFTranscriptomic and Functional Landscape of Adult Human Spinal Cord NSPCs Compared to iPSC-Derived Neural Progenitor Cells.
Cells
January 2025
Department of Neurosciences, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
The adult human spinal cord harbors diverse populations of neural stem/progenitor cells (NSPCs) essential for neuroregeneration and central nervous system repair. While induced pluripotent stem cell (iPSC)-derived NSPCs offer significant therapeutic potential, understanding their molecular and functional alignment with bona fide spinal cord NSPCs is crucial for developing autologous cell therapies that enhance spinal cord regeneration and minimize immune rejection. In this study, we present the first direct transcriptomic and functional comparison of syngeneic adult human NSPC populations, including bona fide spinal cord NSPCs and iPSC-derived NSPCs regionalized to the spinal cord (iPSC-SC) and forebrain (iPSC-Br).
View Article and Find Full Text PDFNatural variations of adolescent neurogenesis and anxiety predict the hierarchical status of adult inbred mice.
EMBO Rep
January 2025
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Prilly, Switzerland.
Hierarchy provides a survival advantage to social animals in challenging circumstances. In mice, social dominance is associated with trait anxiety which is regulated by adult hippocampal neurogenesis. Here, we test whether adolescent hippocampal neurogenesis may regulate social dominance behavior in adulthood.
View Article and Find Full Text PDFPharmacological Enhancement of Adult Hippocampal Neurogenesis Improves Behavioral Pattern Separation in Young and Aged Male Mice.
Biol Psychiatry Glob Open Sci
March 2025
Department of Psychiatry, Division of Systems Neuroscience, Columbia University, New York State Psychiatric Institute, New York, New York.
Background: Impairments in behavioral pattern separation (BPS)-the ability to distinguish between similar contexts or experiences-contribute to memory interference and overgeneralization seen in many neuropsychiatric conditions, including depression, anxiety, posttraumatic stress disorder, dementia, and age-related cognitive decline. Although BPS relies on the dentate gyrus and is sensitive to changes in adult hippocampal neurogenesis, its significance as a pharmacological target has not been tested.
Methods: In this study, we applied a human neural stem cell high-throughput screening cascade to identify compounds that increase human neurogenesis.
Want 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!