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VOL. 74 (3), 387-408, 2008 FINE TUNING NEUROMODULATION BY ADENOSINE...

true in ageing (10) where neuroprotection is hardly needed. There is
a relationship between age-related changes in the density of TrkB
receptors and adenosine A2A receptors on what concerns BDNF-
induced enhancement of synaptic transmission in the hippocampus
(10). This should be taken into consideration whenever evaluating
BDNF actions in nerve cells, and may prove relevant in the design
of BDNF-based therapeutic strategies.

FIGURE 1. Mechanisms involved in the activation adenosine A2A-receptors.
It is proposed an intracellular cascade involving the cyclic AMP/PKA and its
potential relationship with the BDNF enhancement of synaptic transmission.

Also GDNF (14) in striatum promotes release of dopamine. GDNF
has been pointed out as a potential therapeutic approach in the
management of Parkinson’s disease (25). So, the prevention of GDNF
effect by A2A receptor antagonism point towards the need of further
studies on the consequences of long-term therapy with A2A receptor
blockers in neurodegenerative diseases where neurotrophic factors
may play a beneficial role. One issue that should be explored in the
future is the optimal time window for combined beneficial effects
for GDNF and A2A receptor agonists/antagonists. If, in the late stages

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