A brief, but repeated, swimming protocol is sufficient to overcome amyloid β-protein inhibition of hippocampal long-term potentiation

摘要: Alzheimer's disease starts as an almost imperceptible malady, first observed clinically a mild memory problem. Accumulating genetic and biochemical data have suggested that amyloid beta-protein (Abeta) plays important role in this loss, Abeta has been shown to suppress long-term potentiation (LTP), cellular model for learning. Here we show very brief (3 min) swimming, twice daily 2 weeks, rescues LTP inhibition the CA1 region of hippocampal slices caused by Abeta(42) or Abeta(40) carrying Arctic mutation using theta burst stimulation (TBS) protocol. Whereas input-output curve was not affected, paired-pulse ratio reduced mice receiving our repeated swimming protocol, suggesting possible involvement presynaptic facilitation. Similar Abeta's could be rescued with adenylyl cyclase, forskolin. Interestingly, protocol produced conditions which weak-TBS invoke naive mice, again mimicked In contrast, protein kinase A (PKA) inhibitor, H89, blocked both forskolin LTP; these implicate cAMP/PKA signaling protective effect mediating Abeta' detrimental effects. Our add new simple behavior paradigm shows importance environmental factor reversing pathophysiological effects Abeta, suggest therapeutic avenues.