Aging potentiates Aβ-induced depletion of SNAP-25 in mouse hippocampus

Previously we showed that in Tg2576 mouse hippocampus, synaptosomal-associated protein 25 (SNAP-25) immunoreactivity (IR) is Greatly reduced and intracerebroventricular injection of anti-Abeta reverses this depletion. 3- and 24-month-old wild-type mice received juxta-amygdala injection of Abeta42 and hippocampal sections were analyzed for glial fibrillary acidic protein (GFAP)- and SNAP-25-IR at intervals after injections. In young mice, SNAP-IR declined >95% at 1 week in DG-Smi and remained low until 8 weeks, while decreasing in SR, SL and hilum by 8-27% at 1 week and returning to baseline by 2 weeks. There was no change in DG-SMm. In old mice, DG-Smi was specifically depleted in SNAP-IR by >95% even before injection. At 2 weeks, SNAP-IR had declined in all layers by 30-39% of baseline values and by 8 weeks had returned to control values, except the DG-SMm which showed only a 10% reduction at 2 weeks. Baseline GFAP-IR was 10-fold higher in old than in young mice in the fimbria/IC but not appreciably changed in hippocampus. In young mice, the injections of Abeta caused 20-fold increases in GFAP-IR in the fimbria/IC and 2-fold increases in the hippocampal neuropil at 1 week. all of which values returned to baseline by 8 weeks. In old mice, Abeta injections caused relatively much larger increases in GFAP-IR in the hippocampal neuropil than in the fimbria/IC and the GFAP-IR remained greatly increased at 8 weeks. Conclusions: the Abeta effect on presynaptic SNAP-25 depletion is increased with age. DG-SMi shows the most severe changes and therefore may represent the most critical site in hippocampus for Abeta neurotoxicity. Published by Elsevier B.V.