Age-dependent changes in adenosine A1 receptor and uptake site binding in the mouse brain: An autoradiographic study

Ageing is a multifactorial, inevitable event of life span, which affects ne urotransmission in the CNS.:Since adenosine is a major neuromodulator of th e synaptic activity, it was of interest to investigate the possible modific ation of the adenosinergic system in the brain during ageing. Using "in vit ro" quantitative autoradiography and the radioactive ligands [H-3]Cyclohexy ladenosine and [H-3]Nitrobenzylthioinosine, we have studied the distributio n of Al adenosine receptors and adenosine uptake sites in the aged mice (26 months) compared to the young ones (3 months). Our results showed a widesp read reduction in Al receptor binding in the aged animals, which was brain area-specific, occurring in areas where adenosine plays a significant neuro modulatory role such as the hippocampus, cortex, basal ganglia, and thalamu s. Interestingly, the significant reduction in NBI-sensitive adenosine upta ke sites was restricted to few areas of the aged brain, mainly in thalamic nuclei. Since the alterations in the density of Al receptors and adenosine uptake sites showed no regional correlation and since no significant change s in either neuronal or glial cell number ave observed, at least in hippoca mpus and cortex in this mouse strain during ageing, our findings could be e xplained by a selective age-dependent reduction of these adenosinergic comp onents rather than by a general neuronal cell degeneration. As adenosine de presses electrical activity in hippocampus, a downregulation of adenosinerg ic function could probably be related to enhanced excitability seen in hipp ocampal neurons of the CAI subregion and dentate gyrus of aged animals. (C) 2000 Wiley-Liss, Inc.