Sepsis induced denervation-like changes at the neuromuscular junction.
BACKGROUND
The aim of this study was to determine the functional and biochemical changes at the neuromuscular junction (NMJ) induced by sepsis.


METHODS
Male Sprague-Dawley rats were divided into three groups as follows: control, denervation, and sepsis. The rats were subjected to cecal ligation and puncture (CLP) or tibias nerve transection. NMJ function and the area of end plates were assessed, and the protein level of acetylcholine receptors and axonal neuregulin-1 was evaluated on postoperative days 1, 7, and 14.


RESULTS
In the control group, the amplitude of compound muscle action potential (CMAP) was 16.51 ± 2.53 mV. In the sepsis group, the amplitude of CMAP decreased, and duration was prolonged on postoperative days 7 and 14 (P < 0.01). Meanwhile, motor conduction velocity decreased significantly (P < 0.01). CMAP was lost in the denervation group. The twitch tension magnitude gradually declined (P < 0.05) in the sepsis group, although it could not be recorded after lesion. Sepsis and denervation upregulated the expression of γ-nicotinic acetylcholine receptor (nAChR) and α7-nAChR in muscle membrane, compared with those in normal NMJ (261.4 ± 26.5 μm(2)). The NMJ area decreased from 254.6 ± 23.8 μm(2) (1 d after CLP) to 275.4 ± 22.6 μm(2) (7 d after CLP) to 322.7 ± 34.4 μm(2) (14 d after CLP). The postsynaptic NMJ had more discrete fragments (3.84 ± 0.6) compared with the control group (2.13 ± 0.4; P < 0.01). After denervation, NMJ underwent fragmentation and the number of discrete fragments increased (5.57 ± 1.2; P < 0.01). NMJ area increased from 254.6 ± 23.8 μm(2) (1 d after CLP) to 275.4 ± 22.6 μm(2) (7 d after CLP) to 322.7 ± 34.4 μm(2) (14 d after CLP). Sepsis induced neuregulin-1 to decrease from 1 d up to 2 wk compared with the control group (P < 0.05).


CONCLUSIONS
Chronic sepsis has a denervation-like effect on the NMJ, which was indicated by upregulation of heterogeneous nAChRs, the increased area of end plates, and demyelination of the motoneuron axon.
Department of Anesthesiology, The First Affiliated Hospital of Sichuan Medical University, Luzhou, China.
Li
L
Liu
Department of Anesthesiology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Fei
F
Xie
Department of Anesthesiology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Ke
K
Wei
Department of Anesthesiology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xue-Chao
XC
Hao
Department of Anesthesiology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Ping
P
Li
Department of Anesthesiology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Jun
J
Cao
Department of Anesthesiology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: mz89011068@163.com.
Su
S
Min
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003711:Demyelinating Diseases / Q000378:metabolism / Q000503:physiopathology; D003714:Denervation; D004576:Electromyography; D008297:Male; D009469:Neuromuscular Junction / Q000378:metabolism / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology*; D013979:Tibial Nerve / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*
D015415:Biomarkers
Electromyography; Muscle denervation; Neuromuscular junction; Nicotinic; Receptors; Sepsis