title: The preventive effect of NR2B and NR2D-containing NMDAR antagonists on Aβ-induced LTP disruption in the dentate gyrus of rats.
abstract: Amyloid β-protein (Aβ) in the brain of Alzheimer's disease (AD) potently inhibits the synaptic plasticity subsequently causing the cognitive deficits. Long-term potentiation (LTP) of synaptic transmission is thought to be an important cellular mechanism underlying memory formation. Different NR2 subunits are involved in NMDA receptor-dependent LTP. In the present study, we investigated the roles of NR2B and NR2D-containing NMDAR on Aβ(1-42)-induced LTP deficits in the hippocampal slices of rats by using selective NMDAR antagonists. First, we found that Aβ(1-42) significantly inhibited the LTP in the dentate gyrus of slices as reported before. Following that the Aβ(1-42)-induced LTP inhibition was prevented by the pre-perfusion of the specific NR2B-containing NMDAR antagonists ifenprodil (approximately >200-fold selectivity for NR2B) and Ro25-6981 (>3,000-fold selectivity for NR2B), as well as PPDA, a specific NR2D receptor antagonist. Meanwhile, the antagonists on their own had no or only partial effects on the normal LTP in the same dose condition. These findings not only support the effects of NR2B and NR2D subunits on Aβ(1-42)-induced LTP deficits, but also imply that preferentially targeting NR2B- and NR2D-containing NMDARs may provide an effective means to prevent cognitive deficits in the early AD.
authors: Zhejiang Provincial Key Laboratory of Pathophysiology, Department of Physiology and Pharmacology, School of Medicine, Ningbo University, No.818 Fenghua Road, Ningbo, Zhejiang, China, 315211.
authors: Junfang
authors: J
authors: Zhang
authors: Chuang
authors: C
authors: Wang
authors: Tianxiang
authors: T
authors: Deng
authors: Zhancheng
authors: Z
authors: Xue
authors: Xiaowei
authors: X
authors: Chen
authors: Lan
authors: L
authors: Chang
authors: Qinwen
authors: Q
authors: Wang
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects*; D003979:Diazonium Compounds / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D016229:Amyloid beta-Peptides; D003979:Diazonium Compounds; D018691:Excitatory Amino Acid Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D011725:Pyridines; D016194:Receptors, N-Methyl-D-Aspartate; C075222:amyloid beta-protein (1-42); C056729:4-(2'-pyridyldithio)benzyldiazoacetate; C010739:ifenprodil
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