minocycline and Ataxia

Previous studies have reported that microglia depletion leads to impairment of synapse formation and these cells rapidly repopulate from CNS progenitors. However, the impact of microglia depletion and repopulation in the long-term state of the CNS environment has not been characterized. Here, we report that acute and synchronous microglia depletion and subsequent repopulation induces gray matter microgliosis, neuronal death in the somatosensory cortex and ataxia-like behavior. We find a type 1 interferon inflammatory signature in degenerating somatosensory cortex from microglia-depleted mice. Transcriptomic and mass cytometry analysis of repopulated microglia demonstrates an interferon regulatory factor 7-driven activation state. Minocycline and anti-IFNAR1 antibody treatment attenuate the CNS type 1 interferon-driven inflammation, restore microglia homeostasis and reduce ataxic behavior. Neither microglia depletion nor repopulation impact neuropathology or T-cell responses during experimental autoimmune encephalomyelitis. Together, we found that acute microglia ablation induces a type 1 interferon activation state of gray matter microglia associated with acute neurodegeneration.

Topics: Animals; Anti-Bacterial Agents; Ataxia; Cell Death; Encephalomyelitis, Autoimmune, Experimental; Flow Cytometry; Gene Expression Profiling; Gray Matter; Homeostasis; Immunohistochemistry; Interferon Regulatory Factor-7; Interferon Type I; Mice; Microglia; Microscopy, Confocal; Minocycline; Neurons; Receptor, Interferon alpha-beta; Rotarod Performance Test; Somatosensory Cortex

Epileptic seizures cause pathological changes such as sclerosis and pyramidal neuronal loss in the hippocampus. Experimentally, epilepsy can be induced by application of various chemicals directly to the cerebral cortex. In this study, epilepsy was induced in rats by intracortical application of 500 IU penicillin G, and the effect of minocycline and doxycycline on the resulting motor incoordination (rotarod) and hippocampal neuronal loss in CA1, CA2 and CA3 fields (optical fractionator method) were investigated. The rotarod performance was reduced in the epilepsy group to 285.1+/-6.9 s (P<0.05 vs. sham-300 s). Minocycline and doxycycline increased this performance to 297.4+/-1.0 s and 296.9+/-1.2 s respectively. No significant difference was detected between minocycline and doxycycline. The present results also showed that the number of neurons (x10(3)) in the sham group was 150+/-9. In the penicillin-epileptic rats, the number was decreased to 105+/-7 (P<0.01). Minocycline, but not doxycycline (125+/-8), significantly increased the number to 131+/-3 (P<0.05). In conclusion, the second generation tetracycline minocycline decreased the loss of hippocampal neurons and motor incoordination in penicillin-epileptic rats. Minocycline could protect against a variety of neurological insults including epilepsy.

Topics: Animals; Ataxia; Cell Count; Doxycycline; Epilepsy; Hippocampus; Male; Minocycline; Neurons; Neuroprotective Agents; Penicillin G; Rats; Rotarod Performance Test

Cogan's syndrome is a rare clinical entity defined by the association of a nonsyphilitic interstitial keratitis and vestibuloauditory dysfunction, typically Menière's disease-like; the condition has been reported in association with a variety of cutaneous diseases. We now report a case of pyoderma gangrenosum complicating Cogan's syndrome in a 57-year-old woman, which then healed dramatically, as more interestingly did the associated uveitis with minocycline therapy.

Topics: Ataxia; Deafness; Female; Humans; Keratitis; Meniere Disease; Middle Aged; Minocycline; Nausea; Pyoderma Gangrenosum; Syndrome; Uveitis; Vertigo; Vomiting

Minocycline hydrochloride is a tetracycline derivative that has been advocated as the drug of choice in the treatment of meningococcal carriers. Recently, we studied a group of 30 patients who experienced a large number of side-effects after receiving minocycline for treatment of meningococcal meningitis. Twenty-seven of 30 (90%) suffered from dizziness, vertigo, ataxia, weakness, nausea, and vomiting. These symptoms appeared within the first 72 hours of taking minocycline, and disappeared within 48 hours of stopping the medication.

Topics: Adult; Ataxia; Child; Female; Humans; Male; Meningitis, Meningococcal; Minocycline; Nausea; Tetracyclines; Vertigo; Vomiting