Neuroprotective effect of thiamine triethylorthoformate conjugate against Parkinson disease in a mouse model

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Purpose: To investigate the effect of thiamine triethylorthoformate conjugate (TTO) on Parkinson disease (PD) in vitro and in vivo in a mice model. Methods: The effect of TTO on behavioural changes in PD mouse model was studied using pole, traction and swimming tests. Astrocyte proliferation after TTO treatment was assessed using 3 (4, 5 dimethyl 2 thi¬azolyl) 2, 5 diphenyl 2 H tetrazolium bromide (MTT) assay. Apoptosis was determined with flow cytometry using Annexin V Fluorescein isothiocyanate kit. Results: Treatment of PD mice with TTO led to a decrease in climbing time, increase in suspension score and enhancement of swimming score, when compared to the untreated group (p < 0.05). Treatment of astrocytes with TTO prior to MPP incubation significantly increased proliferation (p < 0.05). Apoptosis induction in astrocytes by MPP was attenuated by pre-treatment with TTO. Pre-treatment of astrocytes with 10 µM TTO markedly reduced JNK activation, when compared to astrocytes incubated with MPP alone (p < 0.05). Up-regulation of Bax and down-regulation of Bcl 2 by MPP in astrocytes were attenuated by pre-treatment with TTO. MPP-induced up-regulation of cleaved caspase 3 was suppressed in astrocytes by TTO pre-treatment (p < 0.05). Conclusion: Treatment with TTO prevents MPP+ -induced neuronal damage in vitro in astrocytes and in vivo in mice. The neuro-protective effect of TTO involves down-regulation of JNK activation, inhibition of caspase-3 level, decrease in Bax and increase in Bcl-2 expression. Thus, TTO has a potential for use in the treatment of Parkinson’s disease.

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