| Summary: | 碩士 === 慈濟大學 === 生理暨解剖醫學研究所 === 97 === Many studies have reported that the serum amyloid β-peptide (Aβ) levels are elevated in several mutations linked to familial Alzheimer’s disease (AD). Additionally, hypertensive individuals had increased amount of senile plagues and neurofibrillary in their brain, and a higher chance for developing AD. It has been proposed that the mechanisms of AD pathogenesis may involve a combination of the vascular and neuronal toxicity of Aβ. Studies have reported the vasoactive effects of Aβ on cerebral and peripheral vessels in vitro and in vivo. The effect of Aβ on central control of cardiovascular function is poorly understood. Several in vitro studies reported recently that Aβ affected the function of NMDA receptors, a subtype of ionotropic glutamatergic receptors. This study investigated the effect of Ab on NMDA receptor function in sympathetic preganglionic neurons (SPNs) located in the lateral horn region of spinal cord.
Consecutive applications of NMDA every 5 min induced reproducible changes in membrane potential in SPNs of neonatal rat (7~14 days) spinal cord slice preparation using whole-cell patch recording. Superfusion of Aβ1-40 (0.3 μM) for 5 min caused no change of membrane potentials but significantly potentiated NMDA-induced depolarizations. In contrast, perfusion of Aβ1-42 (0.3
μM) did not influence NMDA-induced depolarizations. Interestingly, perfusion of Aβ25-35 (0.3 μM) significantly inhibited NMDA-induced depolarizations. Western blot analysis showed that incubation of Aβ1-40, but not Aβ1-42 or Aβ25-35, for 30 min onto spinal cord slices increased the levels of phosphoserine 896 on NMDA receptor NR1 subunit in lateral horn regions. In vivo
results showed that intrathecal Ab1-40 (0.2 nmole) potentiated spinal NMDA-induced responses in most of rats tested, but inhibited spinal NMDA-induced responses in few rats examined. Aβ25-35 (0.2 and 0.6 nmole) did not influence spinal NMDA-induced responses. These results suggest that different fragments of Aβ may regulate differentially the NMDA receptor function in rat
sympathetic preganglionic neurons. Whether Aβ plays a role in cardiovascular dysfunction needs to be further examined.
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