title: The hippocampal laminin matrix is dynamic and critical for neuronal survival.
abstract: Laminins are extracellular matrix proteins that participate in neuronal development, survival, and regeneration. During excitotoxin challenge in the mouse hippocampus, neuron interaction with laminin-10 (alpha5,beta1,gamma1) protects against neuronal death. To investigate how laminin is involved in neuronal viability, we infused laminin-1 (alpha1,beta1,gamma1) into the mouse hippocampus. This infusion specifically disrupted the endogenous laminin layer. This disruption was at least partially due to the interaction of the laminin-1 gamma1 chain with endogenous laminin-10, because infusion of anti-laminin gamma1 antibody had the same effect. The disruption of the laminin layer by laminin-1 1) did not require the intact protein because infusion of plasmin-digested laminin-1 gave similar results; 2) was posttranscriptional, because there was no effect on laminin mRNA expression; and 3) occurred in both tPA(-/-) and plasminogen(-/-) mice, indicating that increased plasmin activity was not responsible. Finally, although tPA(-/-) mice are normally resistant to excitotoxin-induced neurodegeneration, disruption of the endogenous laminin layer by laminin-1 or anti-laminin gamma1 antibody renders the tPA(-/-) hippocampal neurons sensitive to kainate. These results demonstrate that neuron interactions with the deposited matrix are not necessarily recapitulated by interactions with soluble components and that the laminin matrix is a dynamic structure amenable to modification by exogenous molecules.
authors.affiliation: Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, New York 10021, USA.
authors.forename: Zu-Lin
authors.initials: ZL
authors.lastname: Chen
authors.forename: Justin A
authors.initials: JA
authors.lastname: Indyk
authors.forename: Sidney
authors.initials: S
authors.lastname: Strickland
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002448:Cell Adhesion; D002470:Cell Survival; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005341:Fibrinolysin / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity; D007797:Laminin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010958:Plasminogen / Q000378:metabolism; D011485:Protein Binding
chemical_list: D007797:Laminin; C121346:laminin 1; C119013:laminin 10; D010958:Plasminogen; D005341:Fibrinolysin; D007608:Kainic Acid