Palmitic acid-enriched diet increases α-synuclein and tyrosine hydroxylase expression levels in the mouse brain

Jared Schommer, Gurdeep Marwarha, Kumi Nagamoto-Combs, Ghribi Othman

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Accumulation of the α-synuclein (α-syn) protein and depletion of dopaminergic neurons in the substantia nigra are hallmarks of Parkinson's disease (PD). Currently, α-syn is under scrutiny as a potential pathogenic factor that may contribute to dopaminergic neuronal death in PD. However, there is a significant gap in our knowledge on what causes α-syn to accumulate and dopaminergic neurons to die. It is now strongly suggested that the nature of our dietary intake influences both epigenetic changes and disease-related genes and may thus potentially increase or reduce our risk of developing PD. Objective: In this study, we determined the extent to which a 3 month diet enriched in the saturated free fatty acid palmitate (PA) influences levels of α-syn and tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis in mice brains. Methods: We fed the m-Thy1-aSyn (m-Thy1) mouse model for PD and its matched control, the B6D2F1/J (B6D2) mouse a PA-enriched diet or a normal diet for 3 months. Levels of α-syn, tyrosine hydroxylase, and the biogenic amines dopamine and dopamine metabolites, serotonin and noradrenaline were determined. Results: We found that the PA-enriched diet induces an increase in α-syn and TH protein and mRNA expression levels in m-Thy1 transgenic mice. We also show that, while it didn't affect levels of biogenic amine content in the B6D2 mice, the PA-enriched diet significantly reduces dopamine metabolites and increases the level of serotonin in m-Thy1 mice. Conclusion: Altogether, our results demonstrate that a diet rich in the saturated fatty acid palmitate can modulate levels of α-syn, TH, dopamine, and serotonin which all are proteins and neurochemicals that play key roles in increasing or reducing the risk for many neurodegenerative diseases including PD.

Original languageEnglish (US)
Article number552
JournalFrontiers in Neuroscience
Volume12
Issue numberAUG
DOIs
StatePublished - Aug 6 2018
Externally publishedYes

Fingerprint

Synucleins
Palmitic Acid
Tyrosine 3-Monooxygenase
Palmitates
Parkinson Disease
Dopamine
Diet
Brain
Serotonin
Biogenic Amines
Dopaminergic Neurons
Fatty Acids
Proteins
Substantia Nigra
Nonesterified Fatty Acids
Epigenomics
Neurodegenerative Diseases
Transgenic Mice
Norepinephrine
Messenger RNA

Keywords

  • A-synuclein
  • Dopamine
  • Palmitic acid
  • Parkinson's disease
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Palmitic acid-enriched diet increases α-synuclein and tyrosine hydroxylase expression levels in the mouse brain. / Schommer, Jared; Marwarha, Gurdeep; Nagamoto-Combs, Kumi; Othman, Ghribi.

In: Frontiers in Neuroscience, Vol. 12, No. AUG, 552, 06.08.2018.

Research output: Contribution to journalArticle

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AB - Background: Accumulation of the α-synuclein (α-syn) protein and depletion of dopaminergic neurons in the substantia nigra are hallmarks of Parkinson's disease (PD). Currently, α-syn is under scrutiny as a potential pathogenic factor that may contribute to dopaminergic neuronal death in PD. However, there is a significant gap in our knowledge on what causes α-syn to accumulate and dopaminergic neurons to die. It is now strongly suggested that the nature of our dietary intake influences both epigenetic changes and disease-related genes and may thus potentially increase or reduce our risk of developing PD. Objective: In this study, we determined the extent to which a 3 month diet enriched in the saturated free fatty acid palmitate (PA) influences levels of α-syn and tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis in mice brains. Methods: We fed the m-Thy1-aSyn (m-Thy1) mouse model for PD and its matched control, the B6D2F1/J (B6D2) mouse a PA-enriched diet or a normal diet for 3 months. Levels of α-syn, tyrosine hydroxylase, and the biogenic amines dopamine and dopamine metabolites, serotonin and noradrenaline were determined. Results: We found that the PA-enriched diet induces an increase in α-syn and TH protein and mRNA expression levels in m-Thy1 transgenic mice. We also show that, while it didn't affect levels of biogenic amine content in the B6D2 mice, the PA-enriched diet significantly reduces dopamine metabolites and increases the level of serotonin in m-Thy1 mice. Conclusion: Altogether, our results demonstrate that a diet rich in the saturated fatty acid palmitate can modulate levels of α-syn, TH, dopamine, and serotonin which all are proteins and neurochemicals that play key roles in increasing or reducing the risk for many neurodegenerative diseases including PD.

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