Cyclic AMP Stimulates Neurite Outgrowth of Lamprey Reticulospinal Neurons without Substantially Altering Their Biophysical Properties

Neuroscience, 2013 · DOI: 10.1016/j.neuroscience.2013.04.016 · Published: August 15, 2013

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Reticulospinal (RS) neurons are critical for initiation of locomotor behavior, and following spinal cord injury (SCI) in the lamprey, the axons of these neurons regenerate and restore locomotor behavior within a few weeks. Activation of cAMP pathways with forskolin or dbcAMP stimulated neurite outgrowth of RS neurons in culture in a PKA-dependent manner, while activation of cGMP signaling pathways with dbcGMP inhibited outgrowth. Taken together, these results suggest that activation of cAMP signaling by dbcAMP stimulates neurite outgrowth, but does not alter the electrical properties of lamprey RS neurons in such a way that would be expected to induce calcium influx.

Study Duration

Not specified

Participants

Larval sea lampreys

Evidence Level

Not specified

Key Findings

1
Activation of cAMP pathways with forskolin or dbcAMP stimulated neurite outgrowth of RS neurons in culture in a PKA-dependent manner.
2
Activation of cGMP signaling pathways with dbcGMP inhibited outgrowth.
3
Forskolin increased action potential duration, which might have increased calcium influx, but did not significantly affect most other electrical properties.

Research Summary

Reticulospinal (RS) neurons are critical for initiation of locomotor behavior, and following spinal cord injury (SCI) in the lamprey, the axons of these neurons regenerate and restore locomotor behavior within a few weeks. Following SCI, second messengers can promote axonal regeneration, but the mechanisms are poorly understood. In conclusion, our results suggest that activation of cAMP pathways alone, without compensation for possible deleterious effects on electrical properties, is an effective approach for stimulating axonal regeneration of RS neuron following SCI.

Practical Implications

SCI Treatment

Activation of cAMP pathways alone is an effective approach for stimulating axonal regeneration of RS neurons following spinal cord injury.

Drug Selection

DbcAMP is identified as a promising agent for stimulating axonal regeneration due to its ability to promote neurite outgrowth without adverse effects on neuronal electrical properties.

Further Research

Further studies could explore the specific PKA-dependent mechanisms involved in cAMP-mediated neurite stimulation.

Study Limitations

1
The specific state of neurons in culture often is not entirely known.
2
The effects of agents on biophysical properties of RS neurons were best determined using isolated brain-spinal cord preparations, which allowed a comparison of drug effects on both injured lamprey RS neurons and uninjured neurons.
3
It was not possible to compare the effects of cAMP activation on both uninjured and uninjured neurons, because the procedure of dissociating the neurons probably resulted in a certain degree of injury.

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