title: Bidirectional changes in water-maze learning following recombinant adenovirus-associated viral vector (rAAV)-mediated brain-derived neurotrophic factor expression in the rat hippocampus.
abstract: Alterations in hippocampal brain-derived neurotrophic factor (BDNF) expression have been implicated in the pathogenesis of emotional and cognitive dysfunction. Here, we induced BDNF overexpression in the rat hippocampus using recombinant adenovirus-associated viral (rAAV) vectors, and studied its long-term (2 months postinduction) effects on anxiety-related behaviour, exploration in the open field, and spatial learning in the water maze. Although the treatment successfully led to substantial elevation of hippocampal BDNF levels, its effect on spatial learning was bidirectional: a subset of rAAV-induced BDNF-overexpressing rats performed well above control level, whereas the rest were clearly impaired. This behavioural distinction corresponded to two markedly different levels of BDNF overexpression. The increase in dorsal hippocampal BDNF content achieved in the 'water-maze-impaired' subgroup was twice that attained in the 'water-maze-improved' rats. Although neither subgroup of rAAV-induced BDNF-overexpressing rats differed from controls in the open field, the 'water-maze-impaired' subgroup also showed a significant anxiolytic effect. Our results suggest that hippocampal BDNF elevation significantly affects cognitive and emotional behaviours, but the direction and magnitude of the effects critically depend on the precise levels of overexpression. This factor must be taken into account in future studies examining the functional consequences of hippocampal BDNF overexpression.
authors.affiliation: Laboratory of Behavioural Neurobiology, ETH Zurich, Switzerland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Pietropaolo
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Paterna
authors.forename: Hansruedi
authors.initials: H
authors.lastname: Büeler
authors.forename: Joram
authors.initials: J
authors.lastname: Feldon
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Yee
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003072:Cognition Disorders / Q000503:physiopathology*; D004644:Emotions / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor