title: Lack of synaptic vesicle protein SV2B protects against amyloid-β₂₅₋₃₅-induced oxidative stress, cholinergic deficit and cognitive impairment in mice.
abstract: SV2B is a synaptic protein widely distributed throughout the brain, which is part of the complex vesicle protein machinery involved in the regulation of synaptic vesicle endocytosis and exocytosis, and therefore in neurotransmitters release. The aims of the present work were twofold: (1) phenotype SV2B knockout mice (SV2B KO) in a battery of cognitive tests; and (2) examine their vulnerability to amyloid-β25-35 (Aβ25-35) peptide-induced toxicity. SV2B KO mice showed normal learning and memory abilities in absence of Aβ25-35 injection. SV2B KO mice were protected against the learning deficits induced after icv injection of an oligomeric preparation of amyloid-β25-35 peptide, as compared to wild-type littermates (SV2B WT). These mice failed to show Aβ25-35-induced impairments in a number of cognitive domains: working memory measured by a spontaneous alternation procedure, recognition memory measured by a novel object recognition task, spatial reference memory assessed in a Morris water-maze, and long-term contextual memory assessed in a inhibitory avoidance task. In addition, SV2B KO mice were protected against Aβ25-35-induced oxidative stress and decrease in ChAT activity in the hippocampus. These data suggest that SV2B could be a key modulator of amyloid toxicity at the synaptic site.
authors.affiliation: UCB Biopharma, Neuroscience Therapeutic Area, Chemin du Foriest, B-1420 Braine-l'Alleud, Belgium. Electronic address: eric.detrait@ucb.com.
authors.forename: Eric
authors.initials: E
authors.lastname: Detrait
authors.affiliation: Amylgen, Parc Scientifique Agropolis 2, 2196, Boulevard de la Lironde, 34980 Montferrier-sur-Lez, France; INSERM U. 710, Université de Montpellier 2, cc 105, Place Eugène Bataillon, 34095 Montpellier cedex 5, France.
authors.forename: Tangui
authors.initials: T
authors.lastname: Maurice
authors.affiliation: UCB Biopharma, Neuroscience Therapeutic Area, Chemin du Foriest, B-1420 Braine-l'Alleud, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Hanon
authors.affiliation: UCB Biopharma, Neuroscience Therapeutic Area, Chemin du Foriest, B-1420 Braine-l'Alleud, Belgium.
authors.forename: Karine
authors.initials: K
authors.lastname: Leclercq
authors.affiliation: UCB Biopharma, Neuroscience Therapeutic Area, Chemin du Foriest, B-1420 Braine-l'Alleud, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Lamberty
mesh_terms: D000109:Acetylcholine / Q000172:deficiency*; D000544:Alzheimer Disease / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000378:metabolism; D008568:Memory / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000633:toxicity*; D021641:Recognition, Psychology / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects; D013572:Synaptic Vesicles / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C489615:Sv2b protein, mouse; C074636:amyloid beta-protein (25-35); D002795:Choline O-Acetyltransferase; D000109:Acetylcholine
keywords: Amyloid; Learning and memory; Oxidative stress; SV2B; Synaptic vesicle