Role of Noradrenergic Inputs From Locus Coeruleus on Changes Induced on Axotomized Motoneurons by Physical Exercise

Front. Cell. Neurosci., 2019 · DOI: 10.3389/fncel.2019.00065 · Published: February 26, 2019

Regenerative Medicine Neurology Rehabilitation

Simple Explanation

This study investigates the role of the locus coeruleus (LC), a noradrenergic center in the brainstem, in the effects of exercise on nerve regeneration after peripheral nerve injury. The LC is activated during stressful situations like intensive exercise. The researchers selectively destroyed the LC in rats before injuring their sciatic nerve. They then subjected the rats to treadmill running and observed the effects on the spinal cord and muscle reinnervation. The study found that the noradrenergic projections from the LC are important for some, but not all, of the effects that exercise induces on the spinal cord after peripheral nerve injury. Specifically, the LC plays a role in preventing synaptic stripping and maintaining perineuronal nets around motoneurons.

Study Duration

75 days

Participants

Adult female Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
Destruction of the LC blocked the ability of treadmill running to prevent synaptic stripping and the reduction in the thickness of perineuronal nets (PNN) on axotomized motoneurons.
2
Treadmill running was still able to attenuate microglia reactivity in animals with a destroyed LC, indicating that this effect is independent of noradrenergic projections from the LC.
3
Animals subjected to treadmill training showed delayed muscle reinnervation, which was more evident in those treated with DSP-4 to destroy the LC.

Research Summary

This study aimed to determine the role of the locus coeruleus (LC) in the effects of treadmill running (TR) on spinal changes after peripheral nerve injury (PNI). The LC was chemically destroyed using DSP-4 prior to sciatic nerve injury in rats. The results showed that LC noradrenergic projections are crucial for the ability of exercise to prevent synaptic stripping and PNN loss around axotomized motoneurons, but not for the attenuation of microglia reactivity. Furthermore, the study indicated that while exercise delays muscle reinnervation, the absence of LC noradrenergic pathways exacerbates this delay. The study concludes that the LC plays a complex role in mediating the effects of exercise on injured motoneurons.

Practical Implications

Rehabilitation Strategies

The study suggests that rehabilitation strategies for peripheral nerve injuries should consider the role of the locus coeruleus and its noradrenergic projections in mediating the benefits of exercise.

Intensity of Exercise

The findings suggest that moderate-intensity exercise protocols may be more beneficial than high-intensity protocols in promoting nerve regeneration and functional recovery after peripheral nerve injury.

Combined Therapies

The study highlights the potential for combining therapeutic approaches to compensate for the limitations of single treatments and optimize outcomes after peripheral nerve injury.

Study Limitations

1
The study was conducted on female rats only, which may limit the generalizability of the findings to males.
2
The use of DSP-4 to destroy the LC may have had off-target effects on other brain regions or neurotransmitter systems.
3
The electrophysiological recovery of the H reflex after PNI does not guarantee the functionality of the stretch reflex.

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