EURON and THEME joint PhD meeting

43
EURON and THEME joint meeting 2011
BDNF signaling in hippocampal learning and memory:
The effects of 7,8-dihydroxyflavone on object memory
E. Bollen 1 , J. De Vry 1 , T. Vanmierlo 1 , H.M.W. Steinbusch 1 , J. Prickaerts 1
1 Dept of Psychiatry and Neuropsychology, Maastricht University, The Netherlands.
Brain derived neurotrophic factor (BDNF) has emerged as an important regulator
of synaptic plasticity in the central nervous system. Binding of BDNF to its main
receptor TrkB activates several intracellular signaling cascades, including the
PLCγ-Ca 2+ pathway, the Ras-mitogen-activated protein kinase (MAPK) pathway
and the phosphatidylinositol 3-kinase (PI3K)-Akt pathways, all of which have
been implicated in neuronal growth and/or plasticity. In hippocampal long-term
potentiation (LTP), one of the most commonly studied forms of plasticity which
is generally considered as the cellular correlate of memory formation, BDNF
has been attributed a critical role. In addition, in previous studies we found that
the cAMP- and cGMP-mediated intracellular signaling cascades are exerting
their specific effects on object memory consolidation via BDNF. Therefore, we
studied the role of TrkB signaling pathways in synaptic plasticity and memory
formation by injecting rats with 7,8-dihydroxyflavone (7,8-DHF; 0.3, 1 and 3
mg/kg), a recently identified TrkB agonist during different consolidation phases
after learning in an object recognition paradigm. Our results show that 7,8-DHF
improves memory when injected both during the early and the late phase of
object memory consolidation at 1 and 3 mg/kg. The lowest dose (0.3 mg/kg)
resulted in a significant memory improvement only when injected at the late
consolidation phase, which may suggest a stronger involvement of BDNF signaling
in late memory consolidation. Taken together, these results show the potential of
7,8-DHF as a cognition enhancer.