Short-term effects of beta-amyloid25-35 peptide aggregates on transmitter release in neuromuscular synapses

Area of Science:

• Neuroscience
• Molecular Biology
• Muscle Physiology

Background:

• The beta-amyloid (Aβ) peptide25-35 is a functional domain of the Aβ precursor protein.
• This domain mediates neurotrophic effects in healthy tissues and neurotoxic effects in Alzheimer disease.
• The presence and role of Aβ in peripheral neuromuscular systems are not fully understood.

Purpose of the Study:

• To investigate the presence of Aβ precursor protein/Aβ peptide in rat intramuscular nerves.
• To examine the short-term functional effects of the Aβ peptide25-35 fragment on acetylcholine release at motor end plates.
• To determine if aggregated Aβ peptide25-35 affects neurotransmission.

Main Methods:

• Immunocytochemistry was used to detect Aβ precursor protein/Aβ peptide in rat Levator auris longus muscles.
• Intracellular recordings were performed on adult and newborn rat motor end plates.
• Acetylcholine release was measured under basal conditions and during electrical stimulation, with and without pharmacological manipulations.

Main Results:

• Aβ precursor protein/Aβ peptide was detected in intramuscular axons, motor nerve terminals, Schwann cells, and the neuromuscular junction.
• Neither monomeric nor aggregated Aβ peptide25-35 (0.1-10 μmol/L) altered evoked or spontaneous acetylcholine release or muscle membrane potential in basal conditions.
• Aggregated Aβ peptide25-35 acutely reduced acetylcholine release (quantal content) during sustained electrical stimulation.

Conclusions:

• The Aβ precursor protein/Aβ peptide is present in the peripheral neuromuscular system.
• Aβ peptide25-35 does not affect basal neurotransmission but can acutely inhibit acetylcholine release when synaptic activity is high.
• The implications of this Aβ-induced inhibition of neurotransmission for Alzheimer disease pathogenesis require further investigation.