Octanoic acid prevents reduction of striatal dopamine in the MPTP mouse model of Parkinson’s disease (original) (raw)

Abstract

Background

Parkinson’s disease (PD) is a progressive neurodegenerative process leading to the loss of dopaminergic neurons and their projections. 1-methyl-4-phenol-1,2,5,6-tetrahydropyridine (MPTP) toxicity is a well-recognized animal model of PD. It is suggested that the impairment of mitochondrial function in the substantia nigra plays an important role in both the onset and the progression of PD.

Octanoic acid (C8), a fatty acid that is the main constituent of the medium-chain triglyceride ketogenic diet, increases the metabolic activity of mitochondria; hence, it seemed interesting to investigate whether C8 exhibits neuroprotective effects in the MPTP model of PD and whether it affects mitochondria function in the striatum.

Methods

Therefore, we examined the possible protective effects of C8 in the mouse model of PD induced by MPTP. For this purpose, changes in the concentration of DA and its metabolites were determined. In addition, we investigated whether expression levels of PGC-1α and the PEPCK enzyme, markers of mitochondrial activity, are altered by C8.

Results

In this study, we observed for the first time that acute and, in particular, repeated administrations of C8 significantly reduced the impairment of dopaminergic neurotransmission in the striatum evoked by MPTP administration and resulted in a marked increase in PGC-1α expression and in both forms of PEPCK.

Conclusions

These results indicate that the C8 leads to an inhibition of the neurodegenerative processes seen after MPTP administration. Our results suggest that a probable mechanism of the neuroprotective action of C8 is related to an increase in metabolic activity in striatal mitochondria.

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Authors and Affiliations

  1. Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology (CePT), Warszawa, Poland
    Ilona Joniec-Maciejak, Adriana Wawer, Piotr Maciejak, Janusz Szyndler, Dagmara Mirowska-Guzel & Adam Płaźnik
  2. Department of Neurochemistry, Institute of Psychiatry and Neurology, Warszawa, Poland
    Danuta Turzyńska, Alicja Sobolewska, Piotr Maciejak & Adam Płaźnik

Authors

  1. Ilona Joniec-Maciejak
  2. Adriana Wawer
  3. Danuta Turzyńska
  4. Alicja Sobolewska
  5. Piotr Maciejak
  6. Janusz Szyndler
  7. Dagmara Mirowska-Guzel
  8. Adam Płaźnik

Corresponding author

Correspondence toIlona Joniec-Maciejak.

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Joniec-Maciejak, I., Wawer, A., Turzyńska, D. et al. Octanoic acid prevents reduction of striatal dopamine in the MPTP mouse model of Parkinson’s disease.Pharmacol. Rep 70, 988–992 (2018). https://doi.org/10.1016/j.pharep.2018.04.008

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