Enhancement of LTP in aged rats is dependent on endogenous BDNF

Maria José Diógenes (1) , Ana Rita Costenla (1) , Luísa Vaqueiro Lopes (1) , André Jerónimo-Santos (1) , Vasco C. Sousa (1) , Bruno Miguel Fontinha (1) , Joaquim Alexandre Ribeiro (1) , Ana Maria Sebastião (1)

1 Institute of Pharmacology and Neurosciences, Faculty of Medicine, and Unit of Neurosciences, Institute of Molecular Medicine

Long-term potentiation (LTP), considered the neurophysiological basis for learning and memory, is facilitated by brain-derived neurotrophic factor (BDNF), an action more evident when LTP is evoked by weak θ-burst stimuli and dependent upon co-activation of adenosine A2A receptors (A2AR), which are more expressed in aged rats. Since θ-burst stimuli also favour LTP in aged animals, we hypothesised that enhanced LTP in ageing could be related to changes in neuromodulation by BDNF. The magnitude of CA1 LTP induced by a weak theta burst stimuli delivered to the Schaffer collaterals was significantly higher in hippocampal slices taken from 36-38 and from 70-80 week old rats, when compared to LTP magnitude in slices from 4 or 10-15 week old rats; this enhancement does not impact in cognitive improvement since aged rats revealed an impairment on hippocampal dependent learning and memory performance, as assessed by the Morris water maze tests. The scavenger for BDNF, TrkB-Fc, and the inhibitor of Trk phosphorylation, K252a, attenuated LTP in slices from 70-80 week old rats, but not from 10-15 week old rats. When exogenously added, BDNF significantly increased LTP in slices from 4 and 10-15 week old rats but did not further increased LTP in 36-38 or 70-80 week old rats. The effects of exogenous BDNF on LTP were prevented by the A2AR antagonist, SCH58261. These results indicate that the higher LTP magnitude observed upon ageing, which does not translate into improved spatial memory performance, is a consequence of an increase in the tonic action of endogenous BDNF.

Mots clés: Cognition; Plasticity; adenosine; neurotrophins; A2A receptors; TrkB receptors; BDNF; Aging; Geriatrics; Neurodegeneration; Neuroprotection

Maria José Diógenes, Ana Rita Costenla, Luísa Vaqueiro Lopes, André Jerónimo-Santos, Vasco C. Sousa, et al.. Enhancement of LTP in aged rats is dependent on endogenous BDNF. Neuropsychopharmacology, 2011, ⟨10.1038/npp.2011.64⟩. ⟨hal-00636192⟩