N-3 PUFA-Deficiency in Early Life Exhibits Aggravated MPTP-Induced Neurotoxicity in Old Age while Supplementation with DHA/EPA-Enriched Phospholipids Exerts a Neuroprotective Effect

Mol Nutr Food Res. 2021 Oct;65(20):e2100339. doi: 10.1002/mnfr.202100339. Epub 2021 Aug 22.

Abstract

Introduction: Malnutrition in early life affects the growth and development of fetus and children, which has a long-term impact on adult health. Previous studies reveal a relationship between dietary omega-3 polyunsaturated fatty acid (n-3 PUFA) content, brain development, and the prevalence of neurodevelopmental disorders and inflammation. However, it is unclear about the effect of n-3 PUFA-deficiency in early life on the development of Parkinson's disease (PD) in old age, as well as the neuroprotective effect of DHA- and EPA-enriched phospholipids (DHA/EPA-PLs) supplemented in old age in long-term n-3 PUFA-deficient mice.

Methods and results: The PD mice induced by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in n-3 PUFA-adequate (N) and -deficient (DEF) group are supplemented with a DHA/EPA-PLs diet for 2 weeks (N+DPL, DEF+DPL). DHA/EPA-PLs supplementation significantly protects against MPTP-induced impairments. The DEF+DPL group shows poorer motor performance, the loss of dopaminergic neurons, mitochondrial dysfunction, and neurodevelopment delay than the N+DPL group, and still did not recover to the Control level.

Conclusions: Dietary n-3 PUFA-deficiency in early life exhibits more aggravated MPTP-induced neurotoxicity in old age, than DHA/EPA-PLs supplementation recovers brain DHA levels and exerts neuroprotective effects in old age in long-term n-3 PUFA-deficient mice, which might provide a potential dietary guidance.

Keywords: DHA- and EPA-enriched phospholipids; MPTP; N-3 PUFA-deficiency; Parkinson's disease; neurotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Brain Chemistry
  • Corpus Striatum / pathology
  • Dietary Supplements
  • Docosahexaenoic Acids / administration & dosage*
  • Eicosapentaenoic Acid / administration & dosage*
  • Fatty Acids / analysis
  • Fatty Acids, Omega-3 / deficiency*
  • Female
  • MPTP Poisoning / prevention & control*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotection*
  • Oxidative Stress
  • Phospholipids / administration & dosage*

Substances

  • Fatty Acids
  • Fatty Acids, Omega-3
  • Phospholipids
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid