title: Prolonged minocycline treatment impairs motor neuronal survival and glial function in organotypic rat spinal cord cultures.
abstract: BACKGROUND
  Minocycline, a second-generation tetracycline antibiotic, exhibits anti-inflammatory and neuroprotective effects in various experimental models of neurological diseases, such as stroke, Alzheimer's disease, amyotrophic lateral sclerosis and spinal cord injury. However, conflicting results have prompted a debate regarding the beneficial effects of minocycline.
  
  
  METHODS
  In this study, we analyzed minocycline treatment in organotypic spinal cord cultures of neonatal rats as a model of motor neuron survival and regeneration after injury. Minocycline was administered in 2 different concentrations (10 and 100 µM) at various time points in culture and fixed after 1 week.
  
  
  RESULTS
  Prolonged minocycline administration decreased the survival of motor neurons in the organotypic cultures. This effect was strongly enhanced with higher concentrations of minocycline. High concentrations of minocycline reduced the number of DAPI-positive cell nuclei in organotypic cultures and simultaneously inhibited microglial activation. Astrocytes, which covered the surface of the control organotypic cultures, revealed a peripheral distribution after early minocycline treatment. Thus, we further analyzed the effects of 100 µM minocycline on the viability and migration ability of dispersed primary glial cell cultures. We found that minocycline reduced cell viability, delayed wound closure in a scratch migration assay and increased connexin 43 protein levels in these cultures.
  
  
  CONCLUSIONS
  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. Further experiments are required to determine the conditions for the safe clinical administration of minocycline in spinal cord injured patients.
authors: Institute of Biochemistry and Cell Biology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany. josephine.pinkernelle@med.ovgu.de
authors: Josephine
authors: J
authors: Pinkernelle
authors: Hisham
authors: H
authors: Fansa
authors: Uwe
authors: U
authors: Ebmeyer
authors: Gerburg
authors: G
authors: Keilhoff
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000633:toxicity; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D008911:Minocycline / Q000494:pharmacology* / Q000633:toxicity; D009046:Motor Neurons / Q000187:drug effects*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D008911:Minocycline
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