Bidirectional changes in water-maze learning following recombinant adenovirus-associated viral vector (rAAV)-mediated brain-derived neurotrophic factor expression in the rat hippocampus.
Behavioural Pharmacology. 2007-09-01; 18(5-6): 533-547
DOI: 10.1097/fbp.0b013e3282da0bf6
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Pietropaolo S(1), Paterna JC, Büeler H, Feldon J, Yee BK.
Author information:
(1)Laboratory of Behavioural Neurobiology, ETH Zurich, Switzerland.
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.