Maternal fish-oil supplementation reduces presenilin 1 level and the amyloid-beta burden in adult 5xFAD offspring without major changes in brain fatty acids

Authors

  • Desanka J. Milanović 1Department of Neurobiology, University of Belgrade, Institute for Biological Research “Siniša Stanković” - National Institute of the Republic of Serbia, University of Belgrade, Blvd. Despot Stefan 142, 11108, Belgrade, Serbia https://orcid.org/0000-0001-9799-0335
  • Milka M. Perović 1Department of Neurobiology, University of Belgrade, Institute for Biological Research “Siniša Stanković” - National Institute of the Republic of Serbia, University of Belgrade, Blvd. Despot Stefan 142, 11108, Belgrade, Serbia https://orcid.org/0000-0003-0941-6988
  • Snježana B. Petrović Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia https://orcid.org/0000-0002-1387-9777
  • Smilja T. Todorović 1Department of Neurobiology, University of Belgrade, Institute for Biological Research “Siniša Stanković” - National Institute of the Republic of Serbia, University of Belgrade, Blvd. Despot Stefan 142, 11108, Belgrade, Serbia https://orcid.org/0000-0001-7155-4914
  • Milica R. Prvulović 1Department of Neurobiology, University of Belgrade, Institute for Biological Research “Siniša Stanković” - National Institute of the Republic of Serbia, University of Belgrade, Blvd. Despot Stefan 142, 11108, Belgrade, Serbia https://orcid.org/0000-0003-2769-5212
  • Anđela P. Vukojević 1Department of Neurobiology, University of Belgrade, Institute for Biological Research “Siniša Stanković” - National Institute of the Republic of Serbia, University of Belgrade, Blvd. Despot Stefan 142, 11108, Belgrade, Serbia https://orcid.org/0000-0003-2465-903X
  • Aleksandra N. Mladenović 1Department of Neurobiology, University of Belgrade, Institute for Biological Research “Siniša Stanković” - National Institute of the Republic of Serbia, University of Belgrade, Blvd. Despot Stefan 142, 11108, Belgrade, Serbia https://orcid.org/0000-0001-9011-5634

Keywords:

Fish oil, maternal treatment, brain fatty acids, omega-3, Alzheimer's disease

Abstract

Paper description:

  • Early diagnosis and treatment of Alzheimer’s disease (AD) are critical for delaying its progression.
  • The 5×FAD (familial AD) mice model develops amyloid pathology very early limiting the window for nutritional intervention.
  • Maternal supplementation with omega-3-reach fish oil until weaning reduces amyloid burden in adult offspring.
  • Early and sufficient omega-3 dietary intervention can enhance brain resilience to AD-related pathology.

Abstract: Omega-3 fatty acid interventions show potential benefits in Alzheimer’s disease (AD) when initiated during its early stages. This study investigated whether maternal diet supplemented with omega-3-rich fish oil (FO) could delay or reduce amyloid beta (Aβ) formation, a key feature of AD, in 5xFAD transgenic offspring. Dams received FO during mating, pregnancy, and lactation. Brain tissues from female offspring were collected at 2 and 6 months of age. The findings indicated a shift in amyloid precursor protein processing, evidenced by increased soluble amyloid precursor protein α (sAPPα) levels, suggesting a transition from amyloidogenic to non-amyloidogenic pathway. FO influenced the expression of presenilin 1 and 2 but did not impact Aβ levels in 2-month-old mice. However, FO reduced the Aβ burden in the brains of 6-month-old animals. Lipidomic analysis revealed that 5xFAD mice have unimpaired omega-3 acquisition during gestation and lactation in comparison to non-transgenic littermates. However, a response to FO supplementation was found in non-transgenic offspring, indicating that alterations in brain lipids are not the primary mechanism of FO-induced Ab decline in 5xFAD. In conclusion, FO did not prevent or delay amyloid pathology in genetically predisposed animals but did mitigate its progression, suggesting mechanisms that warrant further investigation.

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2024-04-24

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Milanović DJ, Perović MM, Petrović SB, Todorović ST, Prvulović MR, Vukojević AP, Mladenović AN. Maternal fish-oil supplementation reduces presenilin 1 level and the amyloid-beta burden in adult 5xFAD offspring without major changes in brain fatty acids. Arch Biol Sci [Internet]. 2024Apr.24 [cited 2024May4];76(1):41-53. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/9386

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Copyright (c) 2024 Desanka Milanović, Milka Perović, Snjezana Petrović, Smilja Todorović, Milica Prvulović, Anđela Vukojević, Aleksandra Mladenović

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