Abstract
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.
Highlights
Parkinson disease (PD) is the second most commonly detected neurodegenerative disorder with morbidity of 2 % in aged people
Movement defect in PD mice model was attenuated by triethylorthoformate conjugate (TTO) treatment
Pole test showed that the time taken for climbing by the mice in negative control and PD groups was almost equal before and after 2 days of MPTP-administration (Figure 1)
Summary
Parkinson disease (PD) is the second most commonly detected neurodegenerative disorder with morbidity of 2 % in aged people. Administration of MPTP to mice causes neuronal death, and leads to symptoms of PD [8]. The neuroprotective effect of thiamine-triethylorthoformate (TTO) conjugate was investigated in vitro on PD astrocytes, and in vivo in PD mice model. Thiamine-triethylorthoformate conjugate was injected to the mice in the treatment groups only on the first day, 45 min before MPTP administration. The pole test was used for the determination of climbing time of mice [11]. Traction test was used for determination of hang time of the mice [12]. The PD astrocyte model was prepared by incubation in DMEM medium containing 4 mM/L MPP+. After 24 h of incubation in DMEM medium, the cells were transferred to the new medium containing MPTP. FACSCantoTM flow cytometer (BD Biosciences) was used for the analysis of cells and determination of apoptosis
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