Abstract
TLR9 is abundant in the central as well as the peripheral nervous systems. Although, motor and sensory abnormalities are reported for TLR9 knock‐out (KO) mice, a physiological role of TLR9 in the nervous system is largely unknown. Since altered synaptic transmission can contribute to sensory and motor abnormalities, we evaluated neuromuscular junction (NMJ) function and morphology of TLR9 KO mice. Triangularis sterni nerve‐muscle preparations were dissected from TLR9 KO and age‐matched control mice. Two electrode voltage clamp of the motor endplate revealed that the amplitude (nAmp) and frequency (sec‐1) of miniature end plate currents (mEPCs) for TLR9 KO NMJs (N=22) increased (p<0.001) to 4.7 ± 0.21 (mean ± SEM) and 52.7 ± 15.04 from the control (N=31) values of 3.5 ± 0.12 and 10.4 ± 1.03. In contrast, mean endplate current (EPC, 1Hz) amplitude was equivalent to control. The ratio of mean EPC to mean mEPC amplitude indicated a decline (p<0.006) of quantal content (m) from the control value (N=14) of 104 ± 5.9 to 80 ± 5.3 for TLR9 KO NMJs (N=13); furthermore, m declined quicker during 50 Hz stimulus trains. A rightward shift of the mEPC amplitude distribution (6240 mEPCs from 22 NMJs of both groups) suggested formation of vesicles containing larger amounts of acetylcholine (ACh). Staining with rhodamine α‐bungarotoxin revealed a decline of endplate volume from 2201 ± 116.0 µm3 (N=36) in control to 1751 ± 89.6 µm3 (N=44) in TLR9 KO mice. This decline of AChRs may result from ACh‐induced decline of AChR expression resulting from increased frequency and amplitude of mEPCs at TLR9 NMJs. At the same time, excessive ACh may induce retrograde suppression of the exocytosis process. Overall, these data suggest a novel role of TLR9 in the maintenance of motor nerve terminal and endplate properties. Supported by The Kirby Foundation
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call