Abstract
Soluble amyloid β1-42 (Aβ1-42) inhibits cholinergic synaptic transmission by reducing ACh release from rat superior cervical ganglion neurons in long-term culture, whereas ACh synthesis and the uptake into synaptic vesicles (SVs) are not affected in the presence of Aβ1-42. To further examine possible mechanisms for Aβ1-42 inhibition of ACh release, effects of Aβ1-42 on SV use and refilling of vesicles pools in the presynaptic terminals were analyzed. The inhibition of neurotransmitter release by Aβ1-42 at 1 μM in the bath occurred in a neural activity-dependent fashion. When SVs were cycled in presynaptic nerve terminals by repetitive stimulation with action potentials (0.2 Hz), Aβ1-42 decreased the size of the readily-releasable pool (RRP) of SVs measured by focal application of a hypertonic solution (0.5 M sucrose), however, the refilling rate of the RRP was not affected after depletion of this pool. After depletion of both the RRP and the reserved pool (RP) of SVs by train of action potentials (5 Hz for 3 min), the refilling rate of the RRP was not affected, but the rate of vesicle entry into the RP was significantly reduced by Aβ1-42. To examine the Aβ1-42 on the classical endocytic vesicle trafficking, a dynamin peptide, the interacting site with amphiphisin, at 1 mM in the pipette, was microinjected into presynaptic neurons along with Aβ1-42. The decrease in EPSP amplitudes was comparable with the dynamin peptide alone. Together, these results suggest that soluble Aβ1-42reduces ACh release by affecting the classical endocytic site in the cholinergic presynaptic terminal. [Jpn J Physiol 55 Suppl:S141 (2005)]
