薬理学講座の鈴木です。
10月15日のNCでは、下記の論文を紹介いたします。
Ageing-induced weakness of mouse NMJs is associated with reduced active
zone density, synaptic event kinetics and presynaptic calcium entry.
Yizhi Li, Elinor H. Case, Christopher Blanchard, Anna Monteleone, Meera
Gandhi, Anousha Jaie, Yomna Badawi, Stephen D. Meriney
Journal of Physiology, 2025
Abstract
Ageing has been shown to affect both the structure and function of the
neuromuscular junction (NMJ). In our previous study, we documented a
biphasic change (first an increase followed by a decrease) in
neurotransmission over the ageing time course at male mouse NMJs. Here,
we explored several potential mechanisms behind the reduction in
presynaptic neurotransmitter release in the later stages of ageing. We
found that the active zone (AZ) density significantly decreased in NMJs
at 30 months, compared to 4- and 26-month-old mice. Furthermore, the
decreased end plate potential (EPP) amplitude in these 30-month-old mice
was associated with a significantly longer rise and decay time, and,
although miniature end plate potential (mEPPs) amplitude and frequency
were unchanged, these events also had a longer rise and decay time.
Thirty-month-old NMJs also showed a significant reduction in the vesicle
replenishment rate (VRR). Additionally, 30–33-month-old NMJs had reduced
presynaptic calcium entry following a single presynaptic action
potential. Taken together, these transmitter release site changes may
explain age-induced reductions in neuromuscular neurotransmission in
aged mice and may also lead to the identification of novel therapeutic
targets or potential biomarkers for future research in this area.