EN
INTRODUCTION: Ketogenic diet (KD) changes energy metabolism by decreasing use of carbohydrates and substituting calories with fatty acids. Neuroprotection is attributed probably due to improved cellular energetics. It has been shown to be beneficial in epilepsy and recently also in neurodegenerative disorders as Parkinson’s Disease (PD). AIM(S): We studied effects of KD in an animal model representing early PD stages to see if KD would influence neuronal degeneration process. METHOD(S): We prepared early PD rat model of selective, medium size nigrostriatal dopaminergic system degeneration by stereotaxic injection of 3 µg /3 µl 6-OHDA into medial forebrain bundle. Ketogenic diet (1% carbohydrates, 70% fat, 8% protein) was started 3 weeks before operation and continued to the end of experiment. RESULTS: KD strongly increased ketone levels in plasma, striatum (STR) and substantia nigra (SN) and lesioning enhanced this effect in plasma 4 days and 2 weeks after operation. KD temporarily increased rats locomotor activity but didn’t rescue neurons from 6-OHDA toxicity, as showed stereological neurons counting and dopamine (DA) levels. Although at the time when locomotor activity was enhanced decrease in DA turnover was observed in SN but not in STR. After 4 weeks this effect was reversed, behaviour normalised and DA turnover in SN increased. Interestingly, lesioned animals kept on KD showed increased levels of succinate in SN at all studied time-points. CONCLUSIONS: We did not observe neuroprotective effect against 6-OHDA induced toxicity, although a modulatory effect in dopaminergic metabolism was detected along with some energetic changes. FINANCIAL SUPPORT: The study was supported by the NCN grant 2012/05/B/NZ4/02599 and statutory funds of the Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland.