TheCa2+ channel inhibitor 2-APB reverses β-amyloid-induced LTP deficit in hippocampus by blocking BAX and caspase-3 hyperactivation

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At the early stage of Alzheimer's disease (AD), the accumulation of β-amyloid (Aβ) oligomers disturbs intracellular Ca2+ homeostasis and disrupts synaptic plasticity of brain neurons. Prevention of Aβ-induced synaptic failure remains an unsolved problem for the treatment of AD. Here, the effects of 2-aminoethoxydiphenyl borate (2-APB), a non-specific, but moderately potent Ca2+ channel inhibitor, on Aβ-induced deficit of synaptic long-term potentiation (LTP) and the underlying molecular mechanisms were explored.


We used hippocampal slices and primary cultures of hippocampal neurons from C57BL/6 mice. Methods applied in our study included electrophysiological recording, membrane protein extraction, Western blot assay and Ca2+ imaging.


2-APB at 10 μM effectively reversed suppression by oligomeric Aβ1–42 (500 nM) of LTP in hippocampal slices. 2-APB also restored phosphorylation and trafficking of the glutamate receptor subunit GluA1 in Aβ-treated hippocampal slices, supporting its protective action on synaptic function. Aβ-mediated abnormal neuronal [Ca2+]i elevation and hyperactivation of the mitochondrial apoptotic proteins BAX, caspase-3, and glycogen synthase kinase-3β, were blocked by 2-APB pretreatment. Moreover, the defict in long term potentiation deficit in hippocampal slices from APPswe/PS1ΔE9 gene mutant mice was rescued by 2-APB at 10 μM.


These data demonstrate that 2-APB is a potentially useful chemical to protect synaptic plasticity against neurotoxic effects of Aβ in AD.

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