title: Enhancement of LTP in aged rats is dependent on endogenous BDNF.
abstract: 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 on co-activation of adenosine A(2A) receptors (A(2A)R), which are more expressed in aged rats. As θ-burst stimuli also favor LTP in aged animals, we hypothesized that enhanced LTP in aging could be related to changes in neuromodulation by BDNF. The magnitude of CA1 LTP induced by a weak θ-burst stimuli delivered to the Schaffer collaterals was significantly higher in hippocampal slices taken from 36 to 38 and from 70 to 80-week-old rats, when compared with LTP magnitude in slices from 4 or 10 to 15-week-old rats; this enhancement does not impact in cognitive improvement as 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 to 80-week-old rats, but not from 10 to 15-week-old rats. When exogenously added, BDNF significantly increased LTP in slices from 4 and 10 to 15-week-old rats, but did not further increased LTP in 36 to 38 or 70 to 80-week-old rats. The effects of exogenous BDNF on LTP were prevented by the A(2A)R antagonist, SCH58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine). These results indicate that the higher LTP magnitude observed upon aging, which does not translate into improved spatial memory performance, is a consequence of an increase in the tonic action of endogenous BDNF.
authors.affiliation: Institute of Pharmacology and Neurosciences, Faculty of Medicine and Unit of Neurosciences, Institute of Molecular Medicine, University of Lisbon, Lisbon, Portugal. diogenes@fm.ul.pt
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Diógenes
authors.forename: Ana R
authors.initials: AR
authors.lastname: Costenla
authors.forename: Luísa V
authors.initials: LV
authors.lastname: Lopes
authors.forename: André
authors.initials: A
authors.lastname: Jerónimo-Santos
authors.forename: Vasco C
authors.initials: VC
authors.lastname: Sousa
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Fontinha
authors.forename: Joaquim A
authors.initials: JA
authors.lastname: Ribeiro
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sebastião
mesh_terms: D000241:Adenosine / Q000502:physiology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology / Q000502:physiology*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism / Q000503:physiopathology*; D009924:Organ Culture Techniques; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D019208:Brain-Derived Neurotrophic Factor; D000241:Adenosine