Matrix metalloproteinase-9 regulates survival of neurons in newborn hippocampus.

The Journal of Biological Chemistry
Sachiko Murase, Ronald D McKay

Abstract

The number of neurons in the adult rodent brain is strongly influenced by events in early postnatal life that eliminate approximately half of the neurons. Recently, we reported that neurotrophins induced survival of neonatal rat hippocampal neurons by promoting neural activity and activation of the Ser/Thr kinase, Akt. The survival of neurons also depended on integrin signaling, but a role for the extracellular matrix (ECM) in this mechanism was yet to be explored. Here, we show that levels of the matrix metalloproteinase-9 (MMP9) decrease, and the level of the ECM protein laminin increases in rat hippocampus during the period of neuronal death. Hippocampi from MMP9 null mice showed higher levels of laminin expression than wild type at P1 and no further increase at P10. In vitro, the matrix metalloproteinase inhibitor FN-439 promoted survival of neurons in a laminin-integrin β1-dependent manner. Blocking laminin signaling attenuated activation of Akt by depolarization. In vivo, injecting FN-439 into the neonatal hippocampus increased the level of laminin and promoted neuronal survival through an integrin-dependent mechanism. These results show signals from the ECM are not simply permissive but rather actively regulated, and the...Continue Reading

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Citations

Oct 11, 2012·Nature Reviews. Neuroscience·George W Huntley
Jul 18, 2015·International Journal of Molecular Sciences·Sachiko Murase
Aug 19, 2015·Frontiers in Cellular Neuroscience·Sarah M ReinhardIryna M Ethell
Jun 22, 2015·Molecular Neurobiology·Sachiko MuraseElizabeth M Quinlan
Apr 17, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sandeep K RaghuwanshiRicardo M Richardson
Jun 1, 2018·Scientific Reports·Steffen VoglerGerd Kempermann
Apr 14, 2017·Cellular and Molecular Neurobiology·Petr NovakPeter Filipcik
Jul 17, 2018·Frontiers in Physiology·Sophie KoszinowskiMelanie Boerries
Oct 2, 2020·Current Opinion in Obstetrics & Gynecology·Ilaha IsaliSherif El-Nashar
Apr 10, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Johanna Seitz-HollandMarek Kubicki

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