The Extracellular Protease Matrix Metalloproteinase-9 Is Activated by Inhibitory Avoidance Learning and Required for Long-Term Memory

Autor/inn/en	Nagy, Vanja; Bozdagi, Ozlem; Huntley, George W.
Titel	The Extracellular Protease Matrix Metalloproteinase-9 Is Activated by Inhibitory Avoidance Learning and Required for Long-Term Memory
Quelle	In: Learning & Memory, 14 (2007) 10, S.655-664 (10 Seiten) PDF als Volltext Verfügbarkeit
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	1072-0502
DOI	10.1101/lm.678307
Schlagwörter	Long Term Memory; Brain; Biochemistry; Learning Processes; Animals; Brain Hemisphere Functions; Task Analysis; Neurological Impairments; Inhibition + Suchen Sie Ihr Suchwort? Langzeitgedächtnis; Gehirn; Biochemie; Learning process; Lernprozess; Animal; Tier; Tiere; Aufgabenanalyse; Neurodegenerative Erkrankung; Hemmung
Abstract	Matrix metalloproteinases (MMPs) are a family of extracellularly acting proteolytic enzymes with well-recognized roles in plasticity and remodeling of synaptic circuits during brain development and following brain injury. However, it is now becoming increasingly apparent that MMPs also function in normal, nonpathological synaptic plasticity of the kind that may underlie learning and memory. Here, we extend this idea by investigating the role and regulation of MMP-9 in an inhibitory avoidance (IA) learning and memory task. We demonstrate that following IA training, protein levels and proteolytic activity of MMP-9 become elevated in hippocampus by 6 h, peak at 12-24 h, then decline to baseline values by [similar to]72 h. When MMP function is abrogated by intrahippocampal infusion of a potent gelatinase (MMP-2 and MMP-9) inhibitor 3.5 h following IA training, a time prior to the onset of training-induced elevation in levels, IA memory retention is significantly diminished when tested 1-3 d later. Animals impaired at 3 d exhibit robust IA memory when retrained, suggesting that such impairment is not likely attributed to toxic or other deleterious effects that permanently disrupt hippocampal function. In anesthetized adult rats, the effective distance over which synaptic plasticity is impaired by a single intrahippocampal infusion of the MMP inhibitor of the kind that blocks IA memory is [similar to]1200 [mu]m. Taken together, these data suggest that IA training induces a slowly emerging, but subsequently protracted period of MMP-mediated proteolysis critical for enabling long-lasting synaptic modification that underlies long-term memory consolidation. (Contains 6 figures.) (Author).
Anmerkungen	Cold Spring Harbor Laboratory Press. 500 Sunnyside Blvd, Woodbury, NY 11797-2924. Tel: 800-843-4388; Tel: 516-367-8800; Fax: 516-422-4097; e-mail: cshpres@cshl.edu; Web site: http://www.learnmem.org/
Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2017/4/10