Beyond the lesion site: minocycline augments inflammation and anxiety-like behavior following SCI in rats through action on the gut microbiota

Journal of Neuroinflammation

Abel Torres-Espin¹  Pamela J. F. Raposo²  Emma K. A. Schmidt³  Keith K. Fenrich⁴  Karim Fouad⁵ 

[1]Department of Neurological Surgery, University of California San Francisco, Brain and Spinal Injury Center, San Francisco, CA, USA

[2]Faculty of Rehabilitation Medicine, University of Alberta, 3-48 Corbett Hall, T6G 2G4, Edmonton, Alberta, Canada

[3]Department of Physical Therapy, University of Alberta, Edmonton, Alberta, Canada

[4]Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada

[5]Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada

[6]Faculty of Rehabilitation Medicine, University of Alberta, 3-48 Corbett Hall, T6G 2G4, Edmonton, Alberta, Canada

[7]Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada

[8]Faculty of Rehabilitation Medicine, University of Alberta, 3-48 Corbett Hall, T6G 2G4, Edmonton, Alberta, Canada

[9]Department of Physical Therapy, University of Alberta, Edmonton, Alberta, Canada

关键词: Spinal cord injury;    Minocycline;    Inflammation;    Microbiota;   

DOI  :  10.1186/s12974-021-02123-0

来源: Springer

【 摘 要 】

BackgroundMinocycline is a clinically available synthetic tetracycline derivative with anti-inflammatory and antibiotic properties. The majority of studies show that minocycline can reduce tissue damage and improve functional recovery following central nervous system injuries, mainly attributed to the drug’s direct anti-inflammatory, anti-oxidative, and neuroprotective properties. Surprisingly the consequences of minocycline’s antibiotic (i.e., antibacterial) effects on the gut microbiota and systemic immune response after spinal cord injury have largely been ignored despite their links to changes in mental health and immune suppression.MethodsHere, we sought to determine minocycline’s effect on spinal cord injury-induced changes in the microbiota-immune axis using a cervical contusion injury in female Lewis rats. We investigated a group that received minocycline following spinal cord injury (immediately after injury for 7 days), an untreated spinal cord injury group, an untreated uninjured group, and an uninjured group that received minocycline. Plasma levels of cytokines/chemokines and fecal microbiota composition (using 16s rRNA sequencing) were monitored for 4 weeks following spinal cord injury as measures of the microbiota-immune axis. Additionally, motor recovery and anxiety-like behavior were assessed throughout the study, and microglial activation was analyzed immediately rostral to, caudal to, and at the lesion epicenter.ResultsWe found that minocycline had a profound acute effect on the microbiota diversity and composition, which was paralleled by the subsequent normalization of spinal cord injury-induced suppression of cytokines/chemokines. Importantly, gut dysbiosis following spinal cord injury has been linked to the development of anxiety-like behavior, which was also decreased by minocycline. Furthermore, although minocycline attenuated spinal cord injury-induced microglial activation, it did not affect the lesion size or promote measurable motor recovery.ConclusionWe show that minocycline’s microbiota effects precede its long-term effects on systemic cytokines and chemokines following spinal cord injury. These results provide an exciting new target of minocycline as a therapeutic for central nervous system diseases and injuries.

【 授权许可】

CC BY