title: Enhanced neuronal plasticity and elevated endogenous sAPPα levels in mice over-expressing MMP9.
abstract: Evidence accumulating during the past few years points to a significant role of matrix metalloproteinase 9 (MMP9) enzymatic activity in synaptic plasticity and cognitive processes. We have previously demonstrated that MMP9 is involved in receptor-mediated α-secretase-like cleavage of APP in vitro, resulting in increased secretion of sAPPα, the soluble N-terminal product of the non-amyloidogenic pathway known to be involved in neuronal plasticity and memory formation. To study the in vivo role of MMP9, we have generated transgenic mice over-expressing MMP9 in the brain. Herein, we demonstrate that MMP9 transgenic animals display enhanced performance in the non-spatial novel object recognition and the spatial water-maze task and that their enhanced performance was accompanied by increased dendritic spine density in the hippocampus and cortex following behavioural testing. Consistent with the above observations, the electrophysiological analysis revealed prolonged maintenance of long-term synaptic potentiation in hippocampal slices from MMP9 transgenic mice. Moreover, elevated sAPPα levels in the hippocampus and cortex of MPP9 transgenic animals were also observed. Overall, our results extend previous findings on the physiological role of MMP9 in neuronal plasticity and furthermore reveal that, APP may be one of the physiological proteolytic targets of MMP9 in vivo.
authors.affiliation: Laboratory of Cell & Matrix Pathobiology, Institute of Biology, NCSR Demokritos, Athens, Greece. apostoliafragkouli@gmail.com
authors.forename: Apostolia
authors.initials: A
authors.lastname: Fragkouli
authors.forename: Costas
authors.initials: C
authors.lastname: Papatheodoropoulos
authors.forename: Spiros
authors.initials: S
authors.lastname: Georgopoulos
authors.forename: Antonios
authors.initials: A
authors.lastname: Stamatakis
authors.forename: Fotini
authors.initials: F
authors.lastname: Stylianopoulou
authors.forename: Effie C
authors.initials: EC
authors.lastname: Tsilibary
authors.forename: Athina K
authors.initials: AK
authors.lastname: Tzinia
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D003071:Cognition / Q000502:physiology; D004247:DNA / Q000235:genetics; D049229:Dendritic Spines / Q000502:physiology; D055724:Electrophysiological Phenomena; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D006801:Humans; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000235:genetics* / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism*; D011597:Psychomotor Performance / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics; D021641:Recognition, Psychology / Q000502:physiology
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D004247:DNA; D020797:Receptor, Platelet-Derived Growth Factor beta; D020780:Matrix Metalloproteinase 9