Ethanol-induced impairment of spatial memory and brain matrix metalloproteinases

Wright, John W.; Masino, Alex J; Reichert, Jennifer R; Turner, Gary D; Meighan, Starla E.; Meighan, Peter C.; Harding, Joseph W.

doi:10.1016/s0006-8993(02)04036-2

Cited by 81 publications

(62 citation statements)

References 63 publications

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“…Thus, the gelatinase MMP-9 protein is highly expressed, predominantly in neurons of the hippocampus and cerebral cortex, where in line with our observation, it is suspected of playing a role in synaptic plasticity (24) and spatial learning (25). Its inhibitor, TIMP-1, also is present in cortical (26) and hippocampal neurons (27).…”

Section: Discussionsupporting

confidence: 84%

Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade

Bruno

Cuello

2006

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

309

279

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In this report, we provide direct demonstration that the neurotrophin nerve growth factor (NGF) is released in the extracellular space in an activity-dependent manner in its precursor form (proNGF) and that it is in this compartment that its maturation and degradation takes place because of the coordinated release and the action of proenzymes and enzyme regulators. This converting protease cascade and its endogenous regulators (including tissue plasminogen activator, plasminogen, neuroserpin, precursor matrix metalloproteinase 9, and tissue inhibitor metalloproteinase 1) are colocalized in neurons of the cerebral cortex and released upon neuronal stimulation. We also provide evidence that this mechanism operates in in vivo conditions, as the CNS application of inhibitors of converting and degrading enzymes lead to dramatic alterations in the tissue levels of either precursor NGF or mature NGF. Pathological alterations of this cascade in the CNS might cause or contribute to a lack of proper neuronal trophic support in conditions such as cerebral ischemia, seizure and Alzheimer's disease or, conversely, to excessive local production of neurotrophins as reported in inflammatory arthritis pain. matrix metalloproteinase 9 ͉ neuroserpin ͉ plasminogen ͉ tissue plasminogen activator ͉ plasmin T he neurotrophin family of growth factors plays a critical role in neuronal survival and differentiation (1, 2). They are produced and liberated in an activity-dependent manner (3) and are responsible for maintaining neuronal phenotype in the adult CNS (4), including the regulation of the steady-state number of synapses (5). These actions are normally attributed to mature neurotrophins, although recently, a biological role for precursor neurotrophin molecules also has been proposed (6, 7). Despite this wealth of knowledge, it is not clear whether these neurotrophins convert to their mature and biologically active form intracellularly or extracellularly, nor is it clear whether, upon their activity-dependent release into the CNS, they are in their mature or precursor form. For example, nerve growth factor (NGF) has been proposed to be released in its mature form (8-10), whereas in the case of BDNF, recent experimental data suggests that the precursor form of BDNF was released and then was processed extracellularly to elicit longterm potentiation (11).These issues are of functional significance because recent in vitro studies with cells transfected with furin-resistant mutated forms of precursor NGF (proNGF) have shown that unprocessed proNGF interacts preferentially with p75 neurotrophin receptor instead of the high-affinity NGF receptor, TrkA, facilitating an apoptotic mechanism in embryonic cells of the peripheral nervous system (7). Moreover, it has been proposed that, in the adult CNS, proNGF expression is up-regulated after CNS lesions, probably contributing to cell death through p75 neurotrophin receptor and sortilin (12, 13). However, other authors have provided evidence suggesting a neurotrophic role for proNGF, albeit to a...

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Section: Discussionsupporting

confidence: 84%

Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade

Bruno

Cuello

2006

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

309

279

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“…Hence, MMP-9 is the first YY1-dependent gene identified in the adult neurons. It codes for an enzyme engaged in the regulation of neuronal plasticity (52)(53)(54) and can also contribute to neuronal cell death in pathological conditions (55). Thus, our data suggest that YY1 can also be implicated in neuronal plasticity as well as in neurodegeneration.…”

Section: Discussionmentioning

confidence: 73%

Yin Yang 1 Is a Critical Repressor of Matrix Metalloproteinase-9 Expression in Brain Neurons

Rylski

Amborska

Zybura

et al. 2008

Journal of Biological Chemistry

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Membrane depolarization controls long lasting adaptive neuronal changes in brain physiology and pathology. Such responses are believed to be gene expression-dependent. Notably, however, only a couple of gene repressors active in nondepolarized neurons have been described. In this study, we show that in the unstimulated rat hippocampus in vivo, as well as in the nondepolarized brain neurons in primary culture, the transcriptional regulator Yin Yang 1 (YY1) is bound to the proximal Mmp-9 promoter and strongly represses Mmp-9 transcription. Furthermore, we demonstrate that monoubiquitinated and CtBP1 (C-terminal binding protein 1)-bound YY1 regulates Mmp-9 mRNA synthesis in rat brain neurons controlling its transcription apparently via HDAC3-dependent histone deacetylation. In conclusion, our data suggest that YY1 exerts, via epigenetic mechanisms, a control over neuronal expression of MMP-9. Because MMP-9 has recently been shown to play a pivotal role in physiological and pathological neuronal plasticity, YY1 may be implicated in these phenomena as well.Neuronal depolarization is important not only for a transmission of information throughout the nervous system but also for an initiation of adaptive neuronal responses to incoming stimuli. Examples of the adaptive changes are long term potentiation and kindling-evoked epileptogenesis believed to underlie physiological (such as learning and memory) and pathological neuronal plasticity, respectively. These long lasting adaptive changes have been linked to an activation of gene expression. Indeed, a number of depolarization-driven gene responses were described over the last 20 years, and in almost all cases inducible transcription factors, like cAMP-response element-binding protein, Elk-1, AP-1, Egrs, etc. (for review see Ref. 1), were found to be responsible for the increased gene expression. However, it is also conceivable to consider a repression of transcription, in addition to its activation, as a means to drive depolarization-evoked gene expression. So far only a very limited number of such repressive molecules has been discovered (2-4).In this study we set out to search for these transcriptional repressors. We focused on a regulation of Mmp-9 that codes for an extracellular matrix protease involved in physiological and pathological extracellular matrix remodeling. Aberrant, and usually excessive, Mmp-9 expression has been linked to numerous disorders of the central nervous system (5-7) as well as other devastating diseases such as tumors (8, 9). Hence, detailed knowledge of its transcriptional repression is of great importance for an understanding of those pathologies and for a potential development of novel therapeutic approaches.Our previous reports have shown that in the nondepolarized rat brain MMP-9 3 is predominantly expressed in neurons (10 -12). However, its expression levels in those cells are very low, which points toward a presence of an efficient mechanism(s) repressing its transcription in unstimulated neurons (10).Molecular mechanisms directly con...

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“…MMP-9 expression is increased in the mouse hippocampus during learning and memory acquisition (Wright et al, 2003) and is regulated in the hippocampus by synaptic activity during dendritic remodeling (Zhang et al, 1998;Szklarczyk et al, 2002). MMP inhibitors also protect hippocampal neurons against kainate-induced excitotoxicity and affects LTP, sprouting and synaptogenesis (Reeves et al, 2003), whereas recombinant MMP-9 induces neuronal death (Jourquin et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Membrane Localization of Membrane Type 5 Matrix Metalloproteinase by AMPA Receptor Binding Protein and Cleavage of Cadherins

et al. 2006

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Ethanol-induced impairment of spatial memory and brain matrix metalloproteinases

Cited by 81 publications

References 63 publications

Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade

Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade

Yin Yang 1 Is a Critical Repressor of Matrix Metalloproteinase-9 Expression in Brain Neurons

Membrane Localization of Membrane Type 5 Matrix Metalloproteinase by AMPA Receptor Binding Protein and Cleavage of Cadherins

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