Age-related decline in cognitive and motor functions could be related to impaired nitric oxide signalling in the striatum, where it is involved in the dynamic regulation of synaptic transmission. Gene array and PCR analyses of striatal tissue showed significant differences between young (2-3-months) and old (18-20 months) mice in transcripts encoding for endothelial nitric oxide synthase, inflammatory and oxidative stress markers and NMDA receptors. The number of GFAP-expressing cells was increased together with higher transcript levels for some glial markers. Field potential recordings from striatal slices prepared from the brains of young and old mice revealed robust age-related differences in synaptic plasticity induced by high-frequency stimulation of the cortical input (HFS) and pharmacological activation of type 1 metabotropic glutamate receptors with (S)-3,5-dihydroxyphenylglycine (DHPG), where nitric oxide plays a permissive role for long-term depression (LTD). Reduced expression of LTD-DHPG in old mice was accompanied by a decreased sensitivity to zaprinast, an inhibitor of cyclic guanosine monophosphate -selective phosphodiesterase. An increased expression of HFS-induced long-term potentiation in the old striatum was not associated with changes in the sensitivity to bath application of NMDA and rolipram, an inhibitor of cyclic adenosine monophosphate-selective phosphodiesterase. Thus impaired nitric oxide signalling observed with aging in different tissues contributes to the change in striatal plasticity.

Supported by Stiftung für Altersforschung, Düsseldorf