Early postnatal expression and localization of matrix metalloproteinases‐2 and ‐9 during establishment of rat hippocampal synaptic circuitry

Aujla, Paven K.; Huntley, George W.

doi:10.1002/cne.23468

Cited by 34 publications

(39 citation statements)

References 80 publications

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“…MMP-9 expression is highest during the period of cell death (first postnatal week) and declines thereafter (Murase & McKay, 2012; Aujla & Huntley, 2014). Critical survival signals for hippocampal neurons during early neonatal development include the cell adhesion molecule integrin β1, which is required for sustained activation of the serine/threonine kinase, Akt (Murase et al , 2011).…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase-9 Regulates Neuronal Circuit Development and Excitability

et al. 2015

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In early postnatal development, naturally occurring cell death, dendritic outgrowth and synaptogenesis sculpt neuronal ensembles into functional neuronal circuits. Here we demonstrate that deletion of the extracellular proteinase MMP-9 affects each of these processes, resulting in maladapted neuronal circuitry. MMP-9 deletion increases the number of CA1 pyramidal neurons, but decreases dendritic length and complexity while dendritic spine density is unchanged. Parallel changes in neuronal morphology are observed in primary visual cortex, and persist into adulthood. Individual CA1 neurons in MMP-9 −/− mice have enhanced input resistance and a significant increase in the frequency, but not amplitude, of miniature excitatory postsynaptic currents (mEPSCs). Additionally, deletion of MMP-9 significant increases spontaneous neuronal activity in awake MMP-9 −/− mice and enhances response to acute challenge by the excitotoxin kainate. Thus MMP-9-dependent proteolysis regulates several aspects of circuit maturation to constrain excitability throughout life.

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Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase-9 Regulates Neuronal Circuit Development and Excitability

et al. 2015

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“…Aujla and Huntley () investigated the hippocampus and found that levels of MMP‐9 transcripts peaked in all hippocampal subfields by PND4 and then declined to adult levels by PND12. The genetic deletion of MMP‐9 was shown to accelerate dendritic spine maturation, showing an early increase in the number of mature mushroom‐shaped spines on PND8.…”

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

311

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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“…Laminin can be targeted and proteolytically cleaved to regulate neuronal function by active matrix metalloproteinases (MMPs), which widely exist in the early developmental period. [25][26][27] A previous study demonstrated that MMP9 can regulate neuronal survival by degrading laminin and modulating the laminin-integrin β1 signaling pathway. 16,28 Moreover, as a zinc-dependent endopeptidase, the activity of MMP9 is closely related to the concentration of free zinc ions.…”

Section: Introductionmentioning

confidence: 99%

Laminin degradation by matrix metalloproteinase 9 promotes ketamine‐induced neuronal apoptosis in the early developing rat retina

Zhang

Sun

et al. 2020

CNS Neurosci Ther

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Aims During early development, laminin degradation contributes to the death of neurons. This study aims to investigate the role and regulation of laminin in ketamine‐induced apoptosis. Methods We performed terminal deoxynucleotidyl transferase biotin‐dUTP nick end labeling (TUNEL) and immunohistochemical assays to investigate the roles of the non‐integrin laminin receptor, matrix metalloproteinase 9 (MMP9) in ketamine‐induced neuronal apoptosis. In situ zymography, Western blot, and immunofluorescence were used to explore the relationships between laminin, MMP9 activity, and Zn2+. Experiments were performed using whole‐mount retinas dissected from Sprague Dawley rats. Results The TUNEL and immunohistochemical assays indicated that ketamine‐induced neuronal apoptosis in early developing rat retina. Blockade of non‐integrin laminin receptor promoted ketamine‐induced apoptosis, while non‐integrin laminin receptor activation attenuated ketamine‐induced apoptosis. Ketamine‐induced laminin degradation, possibly by enhancing the activity of MMP9. MMP9 inhibition reduced ketamine‐induced apoptosis by reducing laminin degradation. Downregulation of Zn2+ attenuated the increased MMP9 activity, laminin degradation caused by ketamine and significantly reduced ketamine‐induced neuronal apoptosis. Conclusion Laminin degradation by MMP9 promoted ketamine‐induced neuronal apoptosis in early developing rat retina. The non‐integrin laminin receptor may be a pathway involved in ketamine‐induced apoptosis. Zn2+ downregulation may play a protective role against ketamine‐induced neuronal apoptosis through inhibiting MMP9 activity.

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Early postnatal expression and localization of matrix metalloproteinases‐2 and ‐9 during establishment of rat hippocampal synaptic circuitry

Cited by 34 publications

References 80 publications

Matrix Metalloproteinase-9 Regulates Neuronal Circuit Development and Excitability

Matrix Metalloproteinase-9 Regulates Neuronal Circuit Development and Excitability

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

Laminin degradation by matrix metalloproteinase 9 promotes ketamine‐induced neuronal apoptosis in the early developing rat retina

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