In Vivo Roles for Matrix Metalloproteinase-9 in Mature Hippocampal Synaptic Physiology and Plasticity

Bozdagi, Ozlem; Nagy, Vanja; Kwei, Kimberly T.; Huntley, George W.

doi:10.1152/jn.00202.2007

Cited by 159 publications

(189 citation statements)

References 92 publications

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“…This has led to the idea that ECM remodeling has an important role in synaptic plasticity. Indeed, evidence suggests that MMP-9 expression is upregulated and the protein becomes proteolytically active during the maintenance phase of LTP at CA3-CA1 synapses in the hippocampus (Nagy et al, 2006;Bozdagi et al, 2007). Similar findings have been recently reported for the rat prefrontal cortex (Okulski et al, 2007).…”

Section: Discussionsupporting

confidence: 85%

Matrix Metalloproteinase-9 Contributes to Kindled Seizure Development in Pentylenetetrazole-Treated Mice by Converting Pro-BDNF to Mature BDNF in the Hippocampus

Mizoguchi¹,

Nakade²,

Terabe³

et al. 2011

J. Neurosci.

174

149

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(Ϫ/Ϫ) mice compared with wild-type mice, an observation that was accompanied by decreased hippocampal levels of mature brain-derived neurotrophic factor. Microinjecting the BDNF scavenger TrkB-Fc into the right ventricle before each PTZ treatment significantly suppressed the development of kindling in wild-type mice, whereas no effect was observed in MMP-9 (Ϫ/Ϫ) mice. On the other hand, bilateral injections of pro-BDNF into the hippocampal dentate gyrus significantly enhanced kindling in wild-type mice but not MMP-9 (Ϫ/Ϫ) mice. These findings suggest that MMP-9 is involved in the progression of behavioral phenotypes in kindled mice because of conversion of pro-BDNF to mature BDNF in the hippocampus.

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Section: Discussionsupporting

confidence: 85%

Matrix Metalloproteinase-9 Contributes to Kindled Seizure Development in Pentylenetetrazole-Treated Mice by Converting Pro-BDNF to Mature BDNF in the Hippocampus

Mizoguchi¹,

Nakade²,

Terabe³

et al. 2011

J. Neurosci.

174

149

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“…S1]. Control experiments verified that the MMP inhibitors had no effects on either basal synaptic transmission, as expected (10,11), or spine volume (Fig. S2).…”

Section: Resultssupporting

confidence: 58%

“…The MMP blockers had no effect on the immediate, TBP-triggered changes in spine size and potentiation, indicating that such rapid plasticity is mechanistically independent of MMP proteolysis. Proteolysis is probably maximally active later than the immediate forms of TBP-triggered plasticity, because increases in MMP-9 levels and proteolysis are detectable by 15-30 min after LTP induction (10,11). NMDA receptors are required for such activation, but the downstream steps that then lead to MMP activation remain unknown and presumably account for some delay.…”

Section: Discussionmentioning

confidence: 99%

“…In brain, they are secreted by neurons and glia in an inactive (pro) form, and they become proteolytically active when several regulatory steps that result in removal of the propeptide are triggered in response to specific stimuli (9). For example, studies have shown that in response to LTP induction, MMP-9 rapidly becomes proteolytically active at perisynaptic sites and essential for maintenance of LTP (10)(11)(12)(13). Thus, perisynaptic MMP-9 proteolysis in response to LTP induction may be critical for local remodeling of dendritic spine structure and function necessary to support long-term synaptic plasticity.…”

mentioning

confidence: 99%

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Extracellular proteolysis by matrix metalloproteinase-9 drives dendritic spine enlargement and long-term potentiation coordinately

Wang

Bozdagi

Nikitczuk

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

295

323

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Persistent dendritic spine enlargement is associated with stable long-term potentiation (LTP), and the latter is thought to underlie long-lasting memories. Extracellular proteolytic remodeling of the synaptic microenvironment could be important for such plasticity, but whether or how proteolytic remodeling contributes to persistent modifications in synapse structure and function is unknown. Matrix metalloproteinase-9 (MMP-9) is an extracellular protease that is activated perisynaptically after LTP induction and required for LTP maintenance. Here, by monitoring spine size and excitatory postsynaptic potentials (EPSPs) simultaneously with combined 2-photon time-lapse imaging and whole-cell recordings from hippocampal neurons, we find that MMP-9 is both necessary and sufficient to drive spine enlargement and synaptic potentiation concomitantly. Both structural and functional MMP-driven forms of plasticity are mediated through ␤1-containing integrin receptors, are associated with integrin-dependent cofilin inactivation within spines, and require actin polymerization. In contrast, postsynaptic exocytosis and protein synthesis are both required for MMP-9-induced potentiation, but not for initial MMP-9-induced spine expansion. However, spine expansion becomes unstable when postsynaptic exocytosis or protein synthesis is blocked, indicating that the 2 forms of plasticity are expressed independently but require interactions between them for persistence. When MMP activity is eliminated during theta-stimulation-induced LTP, both spine enlargement and synaptic potentiation are transient. Thus, MMP-mediated extracellular remodeling during LTP has an instructive role in establishing persistent modifications in both synapse structure and function of the kind critical for learning and memory.actin ͉ cofilin ͉ integrin ͉ synaptic plasticity ͉ protein synthesis L ong-lasting memory is based on long-term modifications of synapse structure and function. In hippocampal area CA1, naturalistic patterns of theta-stimulation readily induce long-term potentiation (LTP) of the excitatory, glutamatergic Schaffer collateral afferent inputs that target dendritic spines (1), which are small, actin-rich dendritic protrusions that harbor the majority of the excitatory synapses (2). Studies show that dendritic spines undergo significant morphological remodeling in association with long-lasting plasticity (3). Spine growth, for example, is associated with the induction of LTP and is thought to be important for supporting persistent changes in synaptic strength (4-6). However, little is known about signals that instruct and coordinate persistent modifications in synapse structure and function during LTP.Dendritic spine morphology and synaptic potentiation can both be dynamically modulated by proteins of the extracellular matrix (ECM) and the cell-surface proteins with which they interact, which has long fueled the idea that regulated ECM remodeling has an important role in synaptic plasticity (7). How precisely such remodeling could occur is not u...

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“…All the alkaloids used in this study significantly reduced MMP -9 activity as well as the expression level. MMP-9 activity is related to many neurodegeneration diseases, for example, MS (Cossins et al, 1997), AD (Deb and Gottschall, 1996), PD (Safciuc et al, 2007), and stroke (Bozdagi et al, 2007).…”

Section: Disscussionmentioning

confidence: 99%

Inhibitory Effects of Coptis japonica Alkaloids on the LPS-Induced Activation of BV2 Microglial Cells

Jeon¹,

Kwon²,

Shin³

et al. 2009

Biomolecules and Therapeutics

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-Coptis japonica (C. japonica) is a perennial medicinal plant that has anti-inflammatory activity. C. japonica contains numerous biologically active alkaloids including berberine, palmatine, epi-berberine, and coptisine. The most well-known anti-inflammatory principal in C. japonica is berberine. For example, berberine has been implicated in the inhibition of iNOS induction by cytokines in microglial cells. However, the efficacies of other alkaloids components on microglial activation were not investigated yet. In this study, we investigated the effects of three alkaloids (palmatine, epi-berberine and coptisine) from C. japonica on lipopolysaccharide (LPS)-induced microglial activation. BV2 microglial cells were immunostimulated with LPS and then the production of several inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS) and matrix metalloproteinase-9 (MMP-9) were examined as well as the phosphorylation status of Erk1/2 mitogen activated protein kinase (MAPK). Palmatine and to a lesser extent epi-berberine and coptisine, significantly reduced the release of NO, which was mediated by the inhibition of LPS-stimulated mRNA and protein induction of inducible nitric oxide synthase (iNOS) from BV2 microglia. In addition to NO, palmatine inhibited MMP-9 enzymatic activity and mRNA induction by LPS. Palmatine also inhibited the increase in the LPS-induced MMP-9 promoter activity determined by MMP-9 promoter luciferase reporter assay. LPS stimulation increased Erk1/2 phosphorylation in BV2 cells and these alkaloids inhibited the LPS-induced phosphorylation of Erk1/2. The anti-inflammatory effect of palmatine in LPS-stimulated microglia may suggest the potential use of the alkaloids in the modulation of neuroinflammatory responses, which might be important in the pathophysiological events of several neurological diseases including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD) and stroke.

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In Vivo Roles for Matrix Metalloproteinase-9 in Mature Hippocampal Synaptic Physiology and Plasticity

Cited by 159 publications

References 92 publications

Matrix Metalloproteinase-9 Contributes to Kindled Seizure Development in Pentylenetetrazole-Treated Mice by Converting Pro-BDNF to Mature BDNF in the Hippocampus

Matrix Metalloproteinase-9 Contributes to Kindled Seizure Development in Pentylenetetrazole-Treated Mice by Converting Pro-BDNF to Mature BDNF in the Hippocampus

Extracellular proteolysis by matrix metalloproteinase-9 drives dendritic spine enlargement and long-term potentiation coordinately

Inhibitory Effects of Coptis japonica Alkaloids on the LPS-Induced Activation of BV2 Microglial Cells

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