PT  - JOURNAL ARTICLE
AU  - Hui Wang
AU  - Lihua Song
AU  - Angela Lee
AU  - Fiona Laird
AU  - Philip C. Wong
AU  - Hey-Kyoung Lee
TI  - Mossy Fiber Long-Term Potentiation Deficits in BACE1 Knock-Outs Can Be Rescued by Activation of α7 Nicotinic Acetylcholine Receptors
AID  - 10.1523/JNEUROSCI.1070-10.2010
DP  - 2010 Oct 13
TA  - The Journal of Neuroscience
PG  - 13808--13813
VI  - 30
IP  - 41
4099  - http://www.jneurosci.org/content/30/41/13808.short
4100  - http://www.jneurosci.org/content/30/41/13808.full
SO  - J. Neurosci.2010 Oct 13; 30
AB  - β-Site amyloid precursor protein-cleaving enzyme 1 (BACE1)—the neuronal β-secretase responsible for producing β-amyloid (Aβ) peptides—emerged as one of the key therapeutic targets of Alzheimer's disease (AD). Although complete ablation of the BACE1 gene prevents Aβ formation, we reported that BACE1 knock-out mice display severe presynaptic deficits at mossy fiber (MF)-to-CA3 synapses in the hippocampus, a major locus of BACE1 expression. We also found that the deficits are likely due to abnormal presynaptic Ca2+ regulation. Cholinergic system has been implicated in AD, in some cases involving Ca2+-permeable α7-nicotinic acetylcholine receptors (nAChRs). Here we report that brief application of nicotine, via α7-nAChRs, can restore MF long-term potentiation in BACE1 knock-outs. Our data suggest that activating α7-nAChRs can recover the presynaptic deficits in BACE1 knock-outs.