Minocycline Mitigation of Tremor Syndrome and Defect of Cognitive and Balance Induced by Harmaline

Abstract

Introduction: Minocycline has anti-inflammatory, anti-apoptotic, and anti-oxidant effects. Preclinical data suggest that minocycline could be beneficial for treating common neurological disorders, including Parkinson disease and multiple sclerosis. Methods: In this study, the effects of minocycline on harmaline-induced motor and cognitive impairments were studied in male Wistar rats. The rats were divided into four groups of ten animals each. Harmaline was used for the induction of Essential Tremor (ET). Minocycline (90 mg/kg, IP) was administered 30 minutes before the saline or harmaline. Tremor intensity, spontaneous locomotor activity, passive avoidance memory, anxiety-related behaviors, and motor function were assessed in the rats. Results: The results showed that minocycline could recover tremor intensity and step width but failed to recuperate the motor balance. The memory impairments observed in harmaline-treated rats were somewhat reversed by administration of minocycline. The cerebellum and inferior olive nucleus were studied for neuronal degeneration using histochemistry and transmission electron microscopy techniques. Harmaline caused ultrastructural changes and neuronal cell loss in inferior olive and cerebellar Purkinje cells. Minocycline exhibited neuroprotective changes on cerebellar Purkinje cells and inferior olivary neurons. Conclusion: These results open new therapeutic perspectives for motor and memory impairments in ET. However, further studies are needed to clarify the exact mechanisms.

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“…In vitro, minocycline addition to 6-OHDA treated PC12 cells suppresses the release of lactate dehydrogenase, reactive oxygen species (ROS) and caspase 3 while supporting the activity of the antioxidant enzymes SOD and catalase [ 251 , 265 , 266 , 267 ]. Of note, these molecular changes seem to explain the increased striatal dopamine levels as well as the cognitive and locomotor improvements observed in zebrafish, mouse, and rat models [ 259 , 260 , 264 , 268 , 269 , 270 , 271 ]. Another mechanism through which minocycline prevents apoptosis is by limiting mitochondria dysfunction, inhibiting caspase 1 and 3 expression, and preventing the degradation of the antiapoptotic protein ICAD (the inhibitor of the caspase-activated deoxyribonuclease) [ 251 , 272 , 273 , 274 ].…”