The abnormal accumulation of amyloid-β peptides (Aβ) is one of the main characteristics of Alzheimer’s disease (AD). Cerebro- and cardiovascular diseases may be the risk factors for developing AD. The effect of Aβ on central sympathetic control of cardiovascular function remains unclear. The present study examines the acute effects of Aβ oligomers on the function of NMDA receptors, a subtype of ionotropic glutamate receptors, in rat sympathetic preganglionic neurons (SPNs). In the in vitro electrophysiological study, Aβ1-40 but not Aβ1-42 applied by superfusion for 5 min significantly potentiated NMDA-induced depolarizations in SPNs of neonatal rat spinal cord slice preparation. Application of Aβ1-40 had little effects on AMPA-induced depolarizations or GABA-induced hyperpolarizations. Treatment with a selective protein kinase C (PKC) inhibitor applied together with Aβ1-40 blocked the augmentation by Aβ1-40 of NMDA-induced depolarizations. Western blot analysis showed an increase in the levels of phosphoserine 896, selectively regulated by PKC, without significant changes in phosphoserine 897 on GluN1 subunits in lateral horn areas of spinal cord slices following treatment with Aβ1-40. In the in vivo study, intrathecal injection of Aβ1-40 (0.2 nmol) potentiated the pressor effects induced by NMDA (2 nmol) injected intrathecally in urethane-anesthetized rats. These results suggest that different fragments of Aβ may have differential effects on the NMDA receptor function and the selective augmentation of NMDA receptor function by Aβ1-40 may involve PKC-dependent mechanisms in sympathetic preganglionic neurons.
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