Enhanced role of adenosine A2A receptors on LTP in the rat hippocampus upon aging
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1
Instituto de Medicina Molecular, University of Lisbon, Institute of Pharmacology and Neurosciences, Faculty of Medicine and Unit of Neurosciences, Portugal
We have recently provided evidence for a particular role of A2A receptor antagonists in the prevention of memory dysfunction after different brain insults known to cause an up-regulation of cortical A2A receptors. Moreover, during aging the density of hippocampal A2A receptors is enhanced and caffeine or A2A receptor antagonists prevent the age-induced memory dysfunction. We also reported that A2A receptors modulate hippocampal synaptic plasticity phenomena such as long-term potentiation (LTP), a neurophysiological correlate of learning and memory. However, it is not known if the impact of A2A receptors in the control of hippocampal LTP also augments on aging.
This was investigated using male Wistar rat hippocampal slices from 3 age groups (young adults: 10-15; middle-age older adults: 36-38; aged: 70-80 weeks old). Two separate sets of the Schaffer afferent pathway were alternately stimulated and the field-excitatory post-synaptic potentials (fEPSP) were extracellularly recorded in the stratum radiatum of the CA1 area. LTP was induced by a high frequency stimulation train (HFS, 100 Hz, 1 s).
An attenuation on the magnitude of the LTP was observed in the presence of the selective A2A receptor antagonist, SCH 58261 (50 nM), in the all age groups, with a larger effect in aged (LTP reduction from 81±7% in the absence to 28±4% in the presence of SCH 58261 (n=5, P<0.05), than in middle-age adults (LTP reduction from 73±5% to 45±6%, n=6, P<0.05). In contrast, the selective A1 receptor antagonist DPCPX (50 nM) increased LTP magnitude in young adult rats (50±10%, n=5 P<0.05) and failed to affect LTP magnitude in the other age groups. This shows that the impact of A2A receptors on LTP is larger in aged rats in accordance with the age- associate increased A2A receptors density and with the ability of A2A receptors to prevent memory dysfunction in aged animals.
Supported by FCT and Pfizer
Conference:
11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009.
Presentation Type:
Poster Presentation
Topic:
Neuronal Communication
Citation:
Costenla
AR,
Diogenes
MJ,
Ribeiro
JA,
Cunha
RA and
De-Mendonca
A
(2009). Enhanced role of adenosine A2A receptors on LTP in the rat hippocampus upon aging.
Front. Neurosci.
Conference Abstract:
11th Meeting of the Portuguese Society for Neuroscience.
doi: 10.3389/conf.neuro.01.2009.11.141
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Received:
11 Aug 2009;
Published Online:
11 Aug 2009.
*
Correspondence:
A. R Costenla, Instituto de Medicina Molecular, University of Lisbon, Institute of Pharmacology and Neurosciences, Faculty of Medicine and Unit of Neurosciences, Lisbon, Portugal, arcostenla@gmail.com