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P1‐123: Brief swimming rescues amyloid‐beta protein inhibition of long‐term potentiation
Author(s) -
Hartley Dean M.,
Li Shaomin
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.710
Subject(s) - long term potentiation , hippocampal formation , excitatory postsynaptic potential , hippocampus , neuroscience , adenylyl cyclase , amyloid beta , forskolin , chemistry , biology , stimulation , medicine , inhibitory postsynaptic potential , disease , receptor
Background: Alzheimer’s disease (AD) starts as an almost imperceptible malady, first observed clinically as a mild memory problem. Accumulating genetic and biochemical data has suggested that amyloid beta-protein (A ) plays an important role in this memory loss and A has been shown to suppress long-term potentiation (LTP), a cellular model for memory and learning. Methods: Mice were placed in a tank for swimming either 2 4 min or 8 12 min with no repetition or twice a day for 2 4 min, each for a total of 14 days. After the swimming protocols, acute hippocampal brain slices were generated to measure field excitatory postsynaptic potentials in the CA1 region before and after theta burst stimulation (TBS) to induce long-term potentiation (LTP), a cellular model of learning and memory. Preparations of A 40 containing the Arctic mutation or A 42 was used to inhibit long-term potentiation. The effect of swimming on A ’s inhibition of LTP was assessed. Results: A very brief (3 min) swimming, twice daily for two weeks, rescues LTP inhibition in the CA1 region of hippocampal slices caused by A 42 or A 40 carrying the Arctic mutation using a TBS protocol. Whereas the input-output curve was not affected, the paired-pulse ratio was reduced in mice receiving our repeated swimming protocol, suggesting a possible involvement of presynaptic facilitation. Similar to swimming, A ’s inhibition of LTP could be rescued with the adenylyl cyclase, forskolin. Interestingly, this swimming protocol produced conditions in which a weak TBS could invoke LTP not observed in naı̈ve mice, which again was mimicked by forskolin. In contrast, the PKA inhibitor, H89, blocked both the forskolin and swimming potentiation of LTP; these data implicate cAMP/PKA signaling in the protective effect of swimming and mediating A detrimental effects. Conclusions: Our data adds a new simple behavior paradigm that shows the importance of an environmental factor in reversing the pathophysiologic effects of A and suggests new therapeutic avenues.