Abstract
BackgroundThere is a meaningful necessity for a targeted therapy of essential tremor (ET), as medications have not been developed specifically for ET. For nearly a century, many drugs have been applied in the treatment of tremor but the drug treatment of ET remains still unknown. Some potential therapeutic factors such fingolimod (FTY720) can be effectively used to treat ET in animals. In the present research, the effect of FTY720, the immunomodulatory sphingosine 1-phosphate (S1P) analog, on degeneration of cerebellar and olivary neurons induced by harmaline in male rats was investigated.MethodsThe animals were allotted into control dimethyl sulfoxide (DMSO), saline + harmaline [30 mg/kg, intraperitoneally, (i.p.)], harmaline + FTY720 (1 mg/kg, i.p, 1 h and 24 h before harmaline injection) groups (n = 10). The cerebellum and inferior olive nucleus (ION) were studied for neuronal degeneration using immunohistochemistry (IHC) and ultrastructural study by transmission electron microscopy (TEM) techniques.ResultsHarmaline caused neuronal cell loss, caspase-3 mediated apoptosis, astrocytosis and ultrastructural changes in cerebellar Purkinje cells and inferior olive neurons. FTY720 exhibited neuroprotective effects on cerebellar Purkinje cells and inferior olivary neurons.ConclusionThese results suggest that FTY720 has potential efficacy for prevention of ET neurodegeneration and astrocytosis induced by harmaline in male rats.
Highlights
Essential tremor (ET) is one of the most prevalent neurological disorder in adults [1, 2], characterised by kinetic and postural oscillation involving a body part or more [3]
This study aimed to investigate the effect of FTY720, the Original Article | Protective effects of fingolimod immunomodulatory sphingosine 1-phosphate (S1P) analog, on the harmaline-induced destruction of cerebellar and olivary neurons in male rats
The results indicated that the number of GFAP+ astrocytes was significantly increased in harmaline group compared to dimethyl sulfoxide (DMSO) group in the cerebellum (P < 0.045) (Figure 1, right panel) and inferior olive nucleus (ION) (P < 0.001) (Figure 1, left panel), and the number of these cells was significantly lower in FTY720 group than harmaline group in the cerebellum (P < 0.006) and ION (P < 0.001)
Summary
Essential tremor (ET) is one of the most prevalent neurological disorder in adults [1, 2], characterised by kinetic and postural oscillation involving a body part or more [3]. Its prevalence estimates ranging from 0.4% to 5% [4]. Despite this high prevalence, the pathogenesis and etiology of ET are not completely known [5]. The harmaline as an indole alkaloid, is a plantderived metabolite used to induce tremor in animals [6]. The effect of FTY720, the immunomodulatory sphingosine 1-phosphate (S1P) analog, on degeneration of cerebellar and olivary neurons induced by harmaline in male rats was investigated
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