{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Legutko D"],"funding":["NIMH NIH HHS","NINDS NIH HHS"],"pubmed_abstract":["Synaptic plasticity underlies learning and memory processes as well as contributes, in its aberrant form, to neuropsychiatric disorders. One of its major forms is structural long-term potentiation (sLTP), an activity-dependent growth of dendritic spines that harbor excitatory synapses. The process depends on the release of brain-derived neurotrophic factor (BDNF), and activation of its receptor, TrkB. Matrix metalloproteinase-9 (MMP-9), an extracellular protease is essential for many forms of neuronal plasticity engaged in physiological as well as pathological processes. Here, we utilized two-photon microscopy and two-photon glutamate uncaging to demonstrate that MMP-9 activity is essential for sLTP and is rapidly (~seconds) released from dendritic spines in response to synaptic stimulation. Moreover, we show that either chemical or genetic inhibition of MMP-9 impairs TrkB activation, as measured by fluorescence lifetime imaging microscopy of FRET sensor. Furthermore, we provide evidence for a cell-free cleavage of proBDNF into mature BDNF by MMP-9. Our findings point to the autocrine mechanism of action of MMP-9 through BDNF maturation and TrkB activation during sLTP."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2023.12.08.569797"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10723398"],"repository":["biostudies-literature"],"pubmed_title":["BDNF signaling requires Matrix Metalloproteinase-9 during structural synaptic plasticity."],"pmcid":["PMC10723398"],"funding_grant_id":["R35 NS116804","R01 MH080047"],"pubmed_authors":["Legutko D","Michaluk P","Kalita K","Yasuda R","Kuzniewska B","Kaczmarek L"],"additional_accession":[]},"is_claimable":false,"name":"BDNF signaling requires Matrix Metalloproteinase-9 during structural synaptic plasticity.","description":"Synaptic plasticity underlies learning and memory processes as well as contributes, in its aberrant form, to neuropsychiatric disorders. One of its major forms is structural long-term potentiation (sLTP), an activity-dependent growth of dendritic spines that harbor excitatory synapses. The process depends on the release of brain-derived neurotrophic factor (BDNF), and activation of its receptor, TrkB. Matrix metalloproteinase-9 (MMP-9), an extracellular protease is essential for many forms of neuronal plasticity engaged in physiological as well as pathological processes. Here, we utilized two-photon microscopy and two-photon glutamate uncaging to demonstrate that MMP-9 activity is essential for sLTP and is rapidly (~seconds) released from dendritic spines in response to synaptic stimulation. Moreover, we show that either chemical or genetic inhibition of MMP-9 impairs TrkB activation, as measured by fluorescence lifetime imaging microscopy of FRET sensor. Furthermore, we provide evidence for a cell-free cleavage of proBDNF into mature BDNF by MMP-9. Our findings point to the autocrine mechanism of action of MMP-9 through BDNF maturation and TrkB activation during sLTP.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jan","modification":"2026-06-05T03:23:35.732Z","creation":"2025-04-04T10:42:28.637Z"},"accession":"S-EPMC10723398","cross_references":{"pubmed":["38106209"],"doi":["10.1101/2023.12.08.569797"]}}