2. Academic Validation
  3. Octanoic acid prevents reduction of striatal dopamine in the MPTP mouse model of Parkinson's disease

Octanoic acid prevents reduction of striatal dopamine in the MPTP mouse model of Parkinson's disease

  • Pharmacol Rep. 2018 Oct;70(5):988-992. doi: 10.1016/j.pharep.2018.04.008.
Ilona Joniec-Maciejak 1,  Adriana Wawer 2,  Danuta Turzyńska 3,  Alicja Sobolewska 3,  Piotr Maciejak 4,  Janusz Szyndler 2,  Dagmara Mirowska-Guzel 2,  Adam Płaźnik 4
Affiliations

Affiliations

  • 1 Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology (CePT), Warszawa, Poland. Electronic address: [email protected].
  • 2 Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology (CePT), Warszawa, Poland.
  • 3 Department of Neurochemistry, Institute of Psychiatry and Neurology, Warszawa, Poland.
  • 4 Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology (CePT), Warszawa, Poland; Department of Neurochemistry, Institute of Psychiatry and Neurology, Warszawa, Poland.
PMID: 30107349 DOI: 10.1016/j.pharep.2018.04.008
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.

Keywords

MPTP; Octanoic acid; PEPCK; PGC-1α; Parkinson’s disease.

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