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MMP AND synapse

Alexander C W Smith, Michael D Scofield, Jasper A Heinsbroek, Cassandra D Gipson, Daniela Neuhofer, Doug J Roberts-Wolfe, Sade Spencer, Neringa M Stankeviciute, Rachel Smith, Nicholas P Allen, Melissa R Lorang, William C Griffin, Heather A Boger, Peter W Kalivas
: Relapse to drug use can be initiated by drug-associated cues. The intensity of cue-induced relapse is correlated with the induction of transient synaptic potentiation (t-SP) at glutamatergic synapses on medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore), and requires spillover of glutamate from prefrontal cortical afferents. We used a rodent self-administration/reinstatement model of relapse to show that cue-induced t-SP and reinstated cocaine-seeking result from glutamate spillover initiating a metabotropic glutamate receptor 5 (mGluR5)-dependent increase in nitric oxide (NO) production...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Behnam Vafadari, Ahmad Salamian, Leszek Kaczmarek
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...
October 2016: Journal of Neurochemistry
Kim Lemmens, Ilse Bollaerts, Stitipragyan Bhumika, Lies de Groef, Jessie Van Houcke, Veerle M Darras, Inge Van Hove, Lieve Moons
Overcoming the failure of axon regeneration in the mammalian central nervous system (CNS) after injury remains a major challenge, which makes the search for proregenerative molecules essential. Matrix metalloproteinases (MMPs) have been implicated in axonal outgrowth during CNS development and show increased expression levels during vertebrate CNS repair. In mammals, MMPs are believed to alter the suppressive extracellular matrix to become more permissive for axon regrowth. We investigated the role of MMPs in axonal regeneration following optic nerve crush (ONC) in adult zebrafish, which fully recover from such injuries due to a high intrinsic axon growth capacity and a less inhibitory environment...
May 1, 2016: Journal of Comparative Neurology
Sarah M Reinhard, Khaleel Razak, Iryna M Ethell
The extracellular matrix (ECM) is a critical regulator of neural network development and plasticity. As neuronal circuits develop, the ECM stabilizes synaptic contacts, while its cleavage has both permissive and active roles in the regulation of plasticity. Matrix metalloproteinase 9 (MMP-9) is a member of a large family of zinc-dependent endopeptidases that can cleave ECM and several cell surface receptors allowing for synaptic and circuit level reorganization. It is becoming increasingly clear that the regulated activity of MMP-9 is critical for central nervous system (CNS) development...
2015: Frontiers in Cellular Neuroscience
Cheng Fu, Dong Chen, Ruijie Chen, Qingsong Hu, Guanghui Wang
Dystrobrevin-binding protein 1 (DTNBP1), a gene encoding dysbindin-1, has been identified as a susceptibility gene for schizophrenia. Functioning with partners in synapses or the cytoplasm, this gene regulates neurite outgrowth and neurotransmitter release. Loss of dysbindin-1 affects schizophrenia pathology. Dysbindin-1 is also found in the nucleus, however, the characteristics of dysbindin in the nucleus are not fully understood. Here, we found that dysbindin-1A is degraded in the nucleus via the ubiquitin-proteasome system and that amino acids 2-41 at the N-terminus are required for this process...
2015: PloS One
Pradip Kumar Kamat, Anuradha Kalani, Naira Metreveli, Suresh C Tyagi, Neetu Tyagi
Ischemic brain stroke is a leading cause of disability and includes hearing loss. Clinical reports have also suggested that there is hearing loss in stroke patients but the mechanism was not determined. Therefore, we hypothesized that hearing loss after cerebral ischemia may be associated with changes to the synapse, gap junction, and sodium channel (NaC) proteins. Ischemia-reperfusion injury was induced in wild-type mice (I/R group). The lesion volume was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining of the brain sections...
July 2015: Canadian Journal of Physiology and Pharmacology
Pradip K Kamat, Philip Kyles, Anuradha Kalani, Neetu Tyagi
Elevated plasma total homocysteine (Hcy) level is associated with an increased risk of Alzheimer's disease (AD). During transsulfuration pathways, Hcy is metabolized into hydrogen sulfide (H2S), which is a synaptic modulator, as well as a neuro-protective agent. However, the role of hydrogen sulfide, as well as N-methyl-D-aspartate receptor (NMDAR) activation, in hyperhomocysteinemia (HHcy) induced blood-brain barrier (BBB) disruption and synaptic dysfunction, leading to AD pathology is not clear. Therefore, we hypothesized that the inhibition of neuronal NMDA-R by H2S and MK801 mitigate the Hcy-induced BBB disruption and synapse dysfunction, in part by decreasing neuronal matrix degradation...
May 2016: Molecular Neurobiology
Katarzyna Lepeta, Leszek Kaczmarek
Recent findings implicate alterations in glutamate signaling, leading to aberrant synaptic plasticity, in schizophrenia. Matrix metalloproteinase-9 (MMP-9) has been shown to regulate glutamate receptors, be regulated by glutamate at excitatory synapses, and modulate physiological and morphological synaptic plasticity. By means of functional gene polymorphism, gene responsiveness to antipsychotics and blood plasma levels MMP-9 has recently been implicated in schizophrenia. This commentary critically reviews these findings based on the hypothesis that MMP-9 contributes to pathological synaptic plasticity in schizophrenia...
September 2015: Schizophrenia Bulletin
Inge Van Hove, Mieke Verslegers, Tjing-Tjing Hu, Martin Carden, Lutgarde Arckens, Lieve Moons
Matrix metalloproteinase-3 (MMP-3) deficiency in mice was previously reported to result in a transiently retarded granule cell migration at postnatal day 8 (P8) and a sustained disturbed arborization of Purkinje cell dendrites from P8 on, concomitant with a delayed synapse formation between granule cells and Purkinje cells and resulting in mild deficits in motor performance in adult animals. However, the molecular mechanisms by which MMP-3 contributes to proper development of the cerebellar cortex during the first postnatal weeks remains unknown...
September 2015: Developmental Neurobiology
Pradip K Kamat, Supriya Swarnkar, Shivika Rai, Vijay Kumar, Neetu Tyagi
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that occurs due to spasms of the neurons, resulting in loss of memory and behavioral changes. In particular, synaptic loss has been described as an early event in the pathogenesis of AD. The increasing evidences have suggested the role of many matrix metalloproteinase (MMPs) in central nervous system (CNS) pathology. Many studies showed that MMPs enzymes are important for the pathophysiological process during Alzheimer's disease (AD). It is usually believed that the synaptic dysfunction and synapse loss contribute to the cognitive deficits of patients with AD...
2014: Therapeutic Targets for Neurological Diseases
Lin Ning, Sonja Paetau, Henrietta Nyman-Huttunen, Li Tian, Carl G Gahmberg
ICAM-5 is a negative regulator of dendritic spine maturation and facilitates the formation of filopodia. Its absence results in improved memory functions, but the mechanisms have remained poorly understood. Activation of NMDA receptors induces ICAM-5 ectodomain cleavage through a matrix metalloproteinase (MMP)-dependent pathway, which promotes spine maturation and synapse formation. Here, we report a novel, ICAM-5-dependent mechanism underlying spine maturation by regulating the dynamics and synaptic distribution of α-actinin...
2015: Biology Open
Alexander C W Smith, Yonatan M Kupchik, Michael D Scofield, Cassandra D Gipson, Armina Wiggins, Charles A Thomas, Peter W Kalivas
Relapse to cocaine use necessitates remodeling excitatory synapses in the nucleus accumbens and synaptic reorganization requires matrix metalloproteinase (MMP) degradation of the extracellular matrix proteins. We found enduring increases in MMP-2 activity in rats after withdrawal from self-administered cocaine and transient increases in MMP-9 during cue-induced cocaine relapse. Cue-induced heroin and nicotine relapse increased MMP activity, and increased MMP activity was required for both cocaine relapse and relapse-associated synaptic plasticity...
December 2014: Nature Neuroscience
Jae-Young Koh, Joon Seo Lim, Hyae-Ran Byun, Min-Heui Yoo
Whereas aberrant brain connectivity is likely the core pathology of autism-spectrum disorder (ASD), studies do not agree as to whether hypo- or hyper-connectivity is the main underlying problem. Recent functional imaging studies have shown that, in most young ASD patients, cerebral cortical regions appear hyperconnected, and cortical thickness/brain size is increased. Collectively, these findings indicate that developing ASD brains may exist in an altered neurotrophic milieu. Consistently, some ASD patients, as well as some animal models of ASD, show increased levels of brain-derived neurotrophic factor (BDNF)...
2014: Molecular Brain
Julie L Chan, Thomas M Reeves, Linda L Phillips
Traumatic brain injury (TBI) produces axotomy, deafferentation and reactive synaptogenesis. Inflammation influences synaptic repair, and the novel brain cytokine osteopontin (OPN) has potential to support axon regeneration through exposure of its integrin receptor binding sites. This study explored whether OPN secretion and proteolysis by matrix metalloproteinases (MMPs) mediate the initial degenerative phase of synaptogenesis, targeting reactive neuroglia to affect successful repair. Adult rats received unilateral entorhinal cortex lesion (UEC) modeling adaptive synaptic plasticity...
November 2014: Experimental Neurology
Emily Pollock, Michelle Everest, Arthur Brown, Michael O Poulter
The integrity and stability of interneurons in a cortical network are essential for proper network function. Loss of interneuron synaptic stability and precise organization can lead to disruptions in the excitation/inhibition balance, a characteristic of epilepsy. This study aimed to identify alterations to the GABAergic interneuron network in the piriform cortex (PC: a cortical area believed to be involved in the development of seizures) after kindling-induced seizures. Immunohistochemistry was used to mark perineuronal nets (PNNs: structures in the extracellular matrix that provide synaptic stability and restrict reorganization of inhibitory interneurons) and interneuron nerve terminals in control and kindled tissues...
October 2014: Neurobiology of Disease
Zsuzsanna Szepesi, Eric Hosy, Blazej Ruszczycki, Monika Bijata, Marta Pyskaty, Arthur Bikbaev, Martin Heine, Daniel Choquet, Leszek Kaczmarek, Jakub Wlodarczyk
Synapses are particularly prone to dynamic alterations and thus play a major role in neuronal plasticity. Dynamic excitatory synapses are located at the membranous neuronal protrusions called dendritic spines. The ability to change synaptic connections involves both alterations at the morphological level and changes in postsynaptic receptor composition. We report that endogenous matrix metalloproteinase (MMP) activity promotes the structural and functional plasticity of local synapses by its effect on glutamate receptor mobility and content...
2014: PloS One
Wenyu Cao, Juan Duan, Xueqin Wang, Xiaolin Zhong, Zhaolan Hu, Fulian Huang, Hongtao Wang, Juan Zhang, Fang Li, Jianyi Zhang, Xuegang Luo, Chang-Qi Li
An enriched environment has been shown to influence brain plasticity and function by involving the action of brain-derived neurotrophic factor (BDNF). BDNF, which is synthesized as a precursor molecule (proBDNF) that undergoes proteolytic cleavage, plays an important role in synaptic plasticity and contributes to several brain functions such as memory, learning, and behavior. The neurotrophins and proneurotrophins often play opposite roles in the brain, suggesting that proteolytic cleavage of proneurotrophins controls the action of neurotrophins...
May 15, 2014: Behavioural Brain Research
Aleksandra Janusz, Jacek Milek, Malgorzata Perycz, Laura Pacini, Claudia Bagni, Leszek Kaczmarek, Magdalena Dziembowska
Activity-dependent protein synthesis at synapses is dysregulated in the Fragile X syndrome (FXS). This process contributes to dendritic spine dysmorphogenesis and synaptic dysfunction in FXS. Matrix Metalloproteinase 9 (MMP-9) is an enzyme involved in activity-dependent reorganization of dendritic spine architecture and was shown to regulate spine morphology in a mouse model of FXS, the Fmr1 knock-out mice. Here we show that MMP-9 mRNA is part of the FMRP complex and colocalizes in dendrites. In the absence of FMRP MMP-9 mRNA translation is increased at synapses, suggesting that this mechanism contributes to the increased metalloproteinase level at synapses of Fmr1 knock-out mice...
November 13, 2013: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Tomasz Wójtowicz, Jerzy W Mozrzymas
Matrix metalloproteases (MMP) play a pivotal role in long-term synaptic plasticity, learning, and memory. The roles of different MMP subtypes are emerging, but the proteolytic activity of certain MMPs was shown to support these processes through the structural and functional modification of hippocampal Schaeffer collateral and mossy fiber (MF) synapses. However, certain patterns of synaptic activity are additionally associated with non-synaptic changes, such as the scaling of neuronal excitability. However, the extent to which MMPs affect this process remains unknown...
February 2014: Hippocampus
Paven K Aujla, George W Huntley
Matrix metalloproteinases (MMPs) are extracellular proteolytic enzymes that contribute to pericellular remodeling in a variety of tissues, including brain, where they function in adult hippocampal synaptic structural and functional plasticity. Synaptic plasticity and remodeling are also important for development of connectivity, but it is unclear whether MMPs--particularly MMP-2 and -9, the major MMPs operative in brain--contribute at these stages. Here, we use a combination of biochemical and anatomical methods to characterize expression and localization of MMP-2 and MMP-9 in early postnatal and adult rat hippocampus...
April 15, 2014: Journal of Comparative Neurology
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