Neural Functions of Matrix Metalloproteinases: Plasticity, Neurogenesis, and Disease

I wish I was smart enough to be able to match this with all the other neurogenesis and neuroplasticity posts I've done.
http://www.hindawi.com/journals/bcri/2012/789083/
AbstractThe brain changes in response to experience and altered environment. To do that, the nervous system often remodels the structures of neuronal circuits. This structural plasticity of the neuronal circuits appears to be controlled not only by intrinsic factors, but also by extrinsic mechanisms including modification of the extracellular matrix. Recent studies employing a range of animal models implicate that matrix metalloproteinases regulate multiple aspects of the neuronal development and remodeling in the brain. This paper aims to summarize recent advances of our knowledge on the neuronal functions of matrix metalloproteinases and discuss how they might relate in neuronal disease.1. IntroductionIn higher vertebrates, the space between neural cells in the brain is filled with material of the extracellular matrix (ECM). Both neurons and glial cells contribute to the production of the ECM components, and the ECM in turn mediates various structural and functional interactions between these cells [1, 2]. During early development, the ECM plays crucial roles in proliferation, migration and differentiation of neural cells. In the mature brain, the ECM undergoes a slow turnover and supports multiple physiological processes. In general, the mature ECM environment seems inhibitory for structural plasticity of neuronal circuits. For example, chondroitin sulfate proteoglycans appear to be one of inhibitory components in the ECM because their degradation by chondroitinase can reactivate ocular dominance plasticity [3]. It is thus likely that regulated proteolytic alteration of the ECM microenvironment should be required for the structural plasticity of neuronal circuits.The ECM modifications in the nervous system are likely achieved by the concerted actions of several different proteases that are secreted by neurons and glial cells [4–6]. Among these proteinases, the matrix metalloproteinases (MMPs) family stands out as likely regulators of the neural plasticity. The mammalian central nervous system (CNS) contains over 10 different MMPs with detectable levels of transcripts or proteins [7, 8]. Studies of the temporal and spatial expression patterns of MMPs in the developing nervous system suggest that MMPs play important roles in neuronal development. In addition, expression of many MMPs has shown to change in response to injury or neurological disease [9]. Knockouts of particular MMPs significantly affect the injury and pathology, indicating that MMPs function as the crucial mediators of neuronal disease [10–12]. Interestingly, several MMP knockouts show deficits in learning and memory [10, 11]. Consistent with these notions, MMPs likely mediate the structural changes of dendritic spines as well as axon/dendrite structures in response to neuronal activity and in mental diseases [10, 11]. This paper considers potential roles for MMPs in neuronal development and plasticity, and discusses its alteration in injury and disease states.