ArticleGeroScience2019
Dysregulation of the SNARE-binding protein Munc18-1 impairs BDNF secretion and synaptic neurotransmission: a novel interventional target to protect the aging brain.
Article in GeroScience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Neural Excitatory/Inhibitory Imbalance in Motor Aging: From Genetic Mechanisms to Therapeutic Challenges.Biology · 2025Review
- Memory Decline and Aberration of Synaptic Proteins in X-Linked Moesin Knockout Male Mice.Psychiatry investigation · 2025Article
- Mechanisms Controlling the Expression and Secretion of BDNF.Biomolecules · 2023Review
- Whole patient knowledge modeling of COVID-19 symptomatology reveals common molecular mechanisms.Frontiers in molecular medicine · 2022Article
- Identification of the protective effect ofPharmaceutical biology · 2021Article
- Dynamic Foot Stimulations During Short-Term Hindlimb Unloading Prevent Dysregulation of the Neurotransmission in the Hippocampus of Rats.Cellular and molecular neurobiology · 2021Article
- Article
- Role of Munc18-1 in the biological functions and pathogenesis of neurological disorders (Review).Molecular medicine reports · 2021Review
- Entacapone Treatment Modulates Hippocampal Proteins Related to Synaptic Vehicle Trafficking.Cells · 2020Article
- The physiology of regulated BDNF release.Cell and tissue research · 2020Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Brain-derived neurotrophic factor (BDNF) has a central role in maintaining and strengthening neuronal connections and to stimulate neurogenesis in the adult brain. Decreased levels of BDNF in the aging brain are thought to usher cognitive impairment. BDNF is stored in dense core vesicles and released through exocytosis from the neurites. The exact mechanism for the regulation of BDNF secretion is not well understood. Munc18-1 (STXBP1) was found to be essential for the exocytosis of synaptic vesicles, but its involvement in BDNF secretion is not known. Interestingly, neurons lacking munc18-1 undergo severe degeneration in knock-out mice. Here, we report the effects of BDNF treatment on the presynaptic terminal using munc18-1-deficient neurons. Reduced expression of munc18-1 in heterozygous (+/-) neurons diminishes synaptic transmitter release, as tested here on individual synaptic connections with FM1-43 fluorescence imaging. Transduction of cultured neurons with BDNF markedly increased BDNF secretion in wild-type but was less effective in munc18-1 +/- cells. In turn, BDNF enhanced synaptic functions and restored the severe synaptic dysfunction induced by munc18-1 deficiency. The role of munc18-1 in the synaptic effect of BDNF is highlighted by the finding that BDNF upregulated the expression of munc18-1 in neurons, consistent with enhanced synaptic functions. Accordingly, this is the first evidence showing the functional effect of BDNF in munc18-1 deficient synapses and about the direct role of munc18-1 in the regulation of BDNF secretion. We propose a molecular model of BDNF secretion and discuss its potential as therapeutic target to prevent cognitive decline in the elderly.
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