Matrix Metalloproteinase (MMP) 9 Transcription in Mouse Brain Induced by Fear Learning

Ganguly, Krishnendu; Rejmak, Emilia; Mikosz, Marta; Nikolaev, Evgeni; Knapska, Ewelina; Kaczmarek, Leszek

doi:10.1074/jbc.m113.457903

Cited by 84 publications

(69 citation statements)

References 50 publications

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“…4A). NFκB is a known regulator of mmp9 expression in other systems (Eberhardt et al, 2002;Ganguly et al, 2013). Using a previously published NFκB reporter line, Tg(NFκB:gfp), we observed an increase in NFκB activity after tail transection by 6 hpw ( Fig.…”

Section: Mmp9 Influences Early Leukocyte Recruitment During Caudal Fimentioning

confidence: 70%

Matrix metalloproteinase 9 modulates collagen matrices and wound repair

et al. 2015

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Acute and chronic injuries are characterized by leukocyte infiltration into tissues. Although matrix metalloproteinase 9 (Mmp9) has been implicated in both conditions, its role in wound repair remains unclear. We previously reported a zebrafish chronic inflammation mutant caused by an insertion in the hepatocyte growth factor activator inhibitor gene 1 (hai1; also known as spint1) that is characterized by epithelial extrusions and neutrophil infiltration into the fin. Here, we performed a microarray analysis and found increased inflammatory gene expression in the mutant larvae, including a marked increase in mmp9 expression. Depletion of mmp9 partially rescued the chronic inflammation and epithelial phenotypes, in addition to restoring collagen fiber organization, as detected by second-harmonic generation imaging. Additionally, we found that acute wounding induces epithelial cell mmp9 expression and is associated with a thickening of collagen fibers. Interestingly, depletion of mmp9 impaired this collagen fiber reorganization. Moreover, mmp9 depletion impaired tissue regeneration after tail transection, implicating Mmp9 in acute wound repair. Thus, Mmp9 regulates both acute and chronic tissue damage and plays an essential role in collagen reorganization during wound repair.

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Section: Mmp9 Influences Early Leukocyte Recruitment During Caudal Fimentioning

confidence: 70%

Matrix metalloproteinase 9 modulates collagen matrices and wound repair

et al. 2015

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“…MMP-9 basal activity was not affected in either of the GSK-3β-modified mice, possibly because of the low levels of constitutive MMP-9 or because its activity is affected in specific subfields of the hippocampus [41, 42, 64, 65]. …”

Section: Discussionmentioning

confidence: 99%

GSK-3β and MMP-9 Cooperate in the Control of Dendritic Spine Morphology

et al. 2016

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Changes in the morphology of dendritic spines are prominent during learning and in different neurological and neuropsychiatric diseases, including those in which glycogen synthase kinase-3β (GSK-3β) has been implicated. Despite much evidence of the involvement of GSK-3β in functional synaptic plasticity, it is unclear how GSK-3β controls structural synaptic plasticity (i.e., the number and shape of dendritic spines). In the present study, we used two mouse models overexpressing and lacking GSK-3β in neurons to investigate how GSK-3β affects the structural plasticity of dendritic spines. Following visualization of dendritic spines with DiI dye, we found that increasing GSK-3β activity increased the number of thin spines, whereas lacking GSK-3β increased the number of stubby spines in the dentate gyrus. Under conditions of neuronal excitation, increasing GSK-3β activity caused higher activity of extracellularly acting matrix metalloproteinase-9 (MMP-9), and MMP inhibition normalized thin spines in GSK-3β overexpressing mice. Administration of the nonspecific GSK-3β inhibitor lithium in animals with active MMP-9 and animals lacking MMP-9 revealed that GSK-3β and MMP-9 act in concert to control dendritic spine morphology. Altogether, our data demonstrate that the dysregulation of GSK-3β activity has dramatic consequences on dendritic spine morphology, implicating MMP-9 as a mediator of GSK-3β-induced synaptic alterations.

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“…Meanwhile, MMP‐9 gene expression is activated through a pathway that involves extracellular signal‐regulated kinases to activate serum response factor to stimulate the expression of the c‐ fos gene and then trigger MMP‐9 gene expression with the aid of AP‐1 transcription factor (Ganguly et al . ; Kuzniewska et al . ).…”

Section: Expression In the Brain And Physiological Rolesmentioning

confidence: 99%

MMP‐9 in translation: from molecule to brain physiology, pathology, and therapy

Vafadari

Salamian

Kaczmarek

2016

Journal of Neurochemistry

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301

257

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Matrix metalloproteinase-9 (MMP-9) is a member of the metzincin family of mostly extracellularly operating proteases. Despite the fact that all of these enzymes might be target promiscuous, with largely overlapping catalogs of potential substrates, MMP-9 has recently emerged as a major and apparently unique player in brain physiology and pathology. The specificity of MMP-9 may arise from its very local and time-restricted actions, even when released in the brain from cells of various types, including neurons, glia, and leukocytes. In fact, the quantity of MMP-9 is very low in the naive brain, but it is markedly activated at the levels of enzymatic activity, protein abundance, and gene expression following various physiological stimuli and pathological insults. Neuronal MMP-9 participates in synaptic plasticity by controlling the shape of dendritic spines and function of excitatory synapses, thus playing a pivotal role in learning, memory, and cortical plasticity. When improperly unleashed, MMP-9 contributes to a large variety of brain disorders, including epilepsy, schizophrenia, autism spectrum disorder, brain injury, stroke, neurodegeneration, pain, brain tumors, etc. The foremost mechanism of action of MMP-9 in brain disorders appears to be its involvement in immune/inflammation responses that are related to the enzyme's ability to process and activate various cytokines and chemokines, as well as its contribution to bloodbrain barrier disruption, facilitating the extravasation of leukocytes into brain parenchyma. However, another emerging possibility (i.e., the control of MMP-9 over synaptic plasticity) should not be neglected. The translational potential of MMP-9 has already been recognized in both the diagnosis and treatment domains. The most striking translational aspect may be the discovery of MMP-9 up-regulation in a mouse model of Fragile X syndrome, quickly followed by human studies and promising clinical trials that have sought to inhibit MMP-9. With regard to diagnosis, suggestions have been made to use MMP-9 alone or combined with tissue inhibitor of matrix metalloproteinase-1 or brain-derived neurotrophic factor as disease biomarkers.

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Matrix Metalloproteinase (MMP) 9 Transcription in Mouse Brain Induced by Fear Learning

Cited by 84 publications

References 50 publications

Matrix metalloproteinase 9 modulates collagen matrices and wound repair

Matrix metalloproteinase 9 modulates collagen matrices and wound repair

GSK-3β and MMP-9 Cooperate in the Control of Dendritic Spine Morphology

MMP‐9 in translation: from molecule to brain physiology, pathology, and therapy

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