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Advisor(s)
Abstract(s)
Adenosine neuromodulation depends on a balanced activation of inhibitory A1 (A1R) and facilitatory A2A receptors (A2AR). Both A1R
and A2AR modulate hippocampal glutamate release and NMDA-dependent long-term potentiation (LTP) but ageing affects the
density of both A1R and A2AR. We tested the effects of selective A1R and A2AR antagonists in the modulation of synaptic
transmission and plasticity in rat hippocampal slices from three age groups (young adults, 2–3 month; middle-aged adults,
6–8 months; aged, 18–20 months). The selective A2AR antagonist SCH58261 (50 nm) attenuated LTP in all age groups, with a larger
effect in aged ()63 ± 7%) than in middle-aged adults ()36 ± 9%) or young adult rats ()36 ± 9%). In contrast, the selective A1R
antagonist DPCPX (50 nm) increased LTP magnitude in young adult rats (+42 ± 6%), but failed to affect LTP magnitude in the other
age groups. Finally, in the continuous presence of DPCPX, SCH58261 caused a significantly larger inhibition of LTP amplitude in
aged ()71 ± 45%) than middle-aged ()28 ± 9%) or young rats ()11 ± 2%). Accordingly, aged rats displayed an increased
expression of A2AR mRNA in the hippocampus and a higher number of glutamatergic nerve terminals equipped with A2AR in aged
(67 ± 6%) compared with middle-aged (34 ± 7%) and young rats (25 ± 5%). The results show an enhanced A2AR-mediated
modulation of LTP in aged rats, in accordance with the age-associated increased expression and density of A2AR in glutamatergic
terminals. This age-associated gain of function of A2AR modulating synaptic plasticity may underlie the ability of A2AR antagonists to
prevent memory dysfunction in aged animals.
Description
Keywords
A1 receptors A2A receptors Adenosine Ageing Hippocampus Synaptic plasticity
Citation
European Journal of Neuroscience, 34 (1), 12-21