LAUSR

Alzheimer’s disease (AD) is a well-known neurodegenerative disease. Deposition of β-amyloid protein (Aβ) oligomers plays a crucial role in the disease progression. Previous studies showed that toxicity induced by Aβ oligomers in cultured neurons and adult rat brain was partially mediated by activation of glutamatergic N-methyl-d-aspartate receptors (NMDAR). Additionally, memantine, a noncompetitive NMDAR antagonist, can significantly improve cognitive functions in some AD patients. However, little is currently known about the potential role of NMDAR antagonist on the regulation of P-MARCKS protein to Aβ1−42 oligomers induced neurotoxicity. The protective effect and mechanism of NMDAR antagonist on primary neurons exposed to Aβ1−42 oligomers were investigated in the study. We have defined that the Aβ1−42 treatment decreased cell viability and increased apoptosis. Moreover, Aβ1−42 oligomers exposure increased P-MARCKS and PIP2 expressions, while decreased SYP expression. However, NMDAR antagonist pretreatment ameliorates Aβ1−42 oligomers induced neuronal apoptosis and partially reverses the expression of P-MARCKS, PIP2 and SYP. In conclusion, NMDAR antagonist may ameliorate neurotoxicity induced by Aβ1−42 oligomers through reducing neuronal apoptosis and protecting synaptic plasticity in rat primary neurons. The mechanism involved may be mediated by the variation of protein P-MARCKS.