Prolonged Minocycline Treatment Impairs Motor Neuronal Survival and Glial Function in Organotypic Rat Spinal Cord Cultures

PLoS ONE, 2013 · DOI: 10.1371/journal.pone.0073422 · Published: August 13, 2013

Simple Explanation

This study investigates the effects of minocycline, a drug with reported neuroprotective properties, on spinal cord tissue cultures from newborn rats. The researchers found that prolonged exposure to minocycline, especially at high doses, actually harmed motor neurons and disrupted the function of glial cells, which are important for supporting and protecting neurons. These findings suggest that using high doses of minocycline to treat spinal cord injuries might have unintended negative consequences.

Study Duration

1 week

Participants

Neonatal rats

Evidence Level

In vitro study

Key Findings

1
Prolonged minocycline administration decreased the survival of motor neurons in the organotypic cultures.
2
High concentrations of minocycline reduced the number of DAPI-positive cell nuclei in organotypic cultures and simultaneously inhibited microglial activation.
3
Minocycline reduced cell viability, delayed wound closure in a scratch migration assay and increased connexin 43 protein levels in these cultures.

Research Summary

The administration of high doses of minocycline was deleterious for motor neuron survival. In addition, it inhibited microglial activation and impaired glial viability and migration. These data suggest that especially high doses of minocycline might have undesired affects in treatment of spinal cord injury.

Practical Implications

Clinical implications

Early minocycline administration in vivo after spinal cord injury should be reconsidered because of the inhibition of beneficial glia functions during the acute phase of the injury.

Treatment Strategies

Administration during the chronic phase with a fully established glia scar may be more promising since minocycline reduced the glia cover in our cultures even after glial formation.

Molecular Target

Cx43 might be a possible molecular target of minocycline. During the early phase of CNS injury, reactive astroglia, which are the major component of the glia scar, appear to have a beneficial effect in regulating the immune response and glutamate balance.

Study Limitations

1
Organotypic cultures are unable to completely model in vivo situations and diseases.
2
Conflicting effects demonstrated in several cell culture studies with minocycline concentrations varying between 10 and 100 µM.
3
Comparison between concentrations used in vitro and in vivo is difficult because of the distinct features of the systems.

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