Abstract
BackgroundPeripheral neuromuscular dysfunctions were found in elderly individuals, and spinal microglia/monocyte plays an important role on this process. This study aims to test whether the glial cell line-derived neurotrophic factor (GDNF) could attenuate age-related neuromuscular dysfunction by inhibiting the activation of spinal microglia/monocyte.MethodsMale Sprague-Dawley rats were divided into an adult group and an aged group. The aged rats were intrathecally injected with normal saline (NS) and GDNF. All the rats were harvested 5 days after each injection. The muscular function was tested by compound muscle action potential, and the activation of microglia/monocyte was detected by immunofluorescence staining; cytokines were assayed by enzyme-linked immunosorbent assay; the expression level of GDNF and its known receptor GFR-α in the spinal cord, the expression level of neuregulin-1 (NRG-1) in the sciatic nerve, and the expression level of γ- and α7- ε-nicotinic acetylcholine receptors in the tibialis anterior muscle were measured by western blotting.ResultsThe activated microglia/monocyte was found in the aged rats compared to the adult rats. The aged rats showed a significant neuromuscular dysfunction and cytokine release as well as increased expression of γ- and α7-nAChR. The protein expression of GDNF, GFR-α, and NRG-1 in the aged rats were significantly lower than that in the adult rats. However, the exogenous injection of GDNF could alleviate the neuromuscular dysfunction but not inhibit the activation of spinal microglia/monocyte. Furthermore, the levels of GFR-α and NRG-1 also increased after GDNF treatment.ConclusionThe GDNF could attenuate the age-related peripheral neuromuscular dysfunction without inhibiting the activation of microglia/monocyte in the spinal cord.
Highlights
Peripheral neuromuscular dysfunctions were found in elderly individuals, and spinal microglia/ monocyte plays an important role on this process
The peripheral motor nerve plays an important role in muscular function, the central nervous system contributes to muscular function in the elderly individuals
In this study, we showed that the glial cell line-derived neurotrophic factor (GDNF) attenuates the age-related neuromuscular dysfunction without inhibiting the activation of spinal microglia/monocyte
Summary
Peripheral neuromuscular dysfunctions were found in elderly individuals, and spinal microglia/ monocyte plays an important role on this process. The peripheral motor nerve plays an important role in muscular function, the central nervous system contributes to muscular function in the elderly individuals. Other studies suggest that the aged microglia/monocyte cell becomes activated and leads to a status of “para-inflammation” [10,11,12], which is between basal homeostatic conditions and true inflammation. Even if this para-inflammation is slight, it is still detrimental to the CNS [13], and eventually aggravates peripheral motor nerve injury [14]. This indicates that peripheral nerve demyelination and muscular dysfunction may be a result of spinal cord inflammation [15]
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