June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
N-3 polyunsaturated fatty acids (n-3 PUFA) prevent traumatic brain injury (TBI)-mediated visual and motor deficits in mice by suppressing ceramide biosynthesis
Author Affiliations & Notes
  • Koushik Mondal
    Ophthalmology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Haruka Takahashi
    Animal Science, Iwate Daigaku, Morioka, Iwate, Japan
  • Jerome Cole II
    Ophthalmology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Nobel Del Mar
    Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Chunyan Li
    Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Daniel Stephenson
    Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Florida, United States
  • Charles Chalfant
    Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Florida, United States
  • Jeremy Allegood
    Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, United States
  • Lauren A Cowart
    Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, United States
  • Anton Reiner
    Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Nawajes A Mandal
    Ophthalmology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
    Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Footnotes
    Commercial Relationships   Koushik Mondal, None; Haruka Takahashi, None; Jerome Cole II, None; Nobel Del Mar, None; Chunyan Li, None; Daniel Stephenson, None; Charles Chalfant, None; Jeremy Allegood, None; Lauren Cowart, None; Anton Reiner, None; Nawajes Mandal, None
  • Footnotes
    Support  NH Grant EY031316; DOD W81XWH2010900; RPB
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 3030. doi:
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      Koushik Mondal, Haruka Takahashi, Jerome Cole II, Nobel Del Mar, Chunyan Li, Daniel Stephenson, Charles Chalfant, Jeremy Allegood, Lauren A Cowart, Anton Reiner, Nawajes A Mandal; N-3 polyunsaturated fatty acids (n-3 PUFA) prevent traumatic brain injury (TBI)-mediated visual and motor deficits in mice by suppressing ceramide biosynthesis. Invest. Ophthalmol. Vis. Sci. 2021;62(8):3030.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Traumatic brain injury (TBI) causes neuroinflammation and neurodegeneration leading to various pathological complications such as motor, and sensory (visual) deficits, cognitive deficit, and depression. N-3 polyunsaturated fatty acid (n-3 PUFA) containing lipids are known to be anti-inflammatory, whereas sphingolipid, ceramide (Cer) is an inducer of neuroinflammation and degeneration. The purpose of this study was to understand whether the presence of an elevated systemic level of n-3 PUFA in the Fat1-transgenic mice is associated with the prevention of TBI-mediated sensory-motor deficits by preventing Cer generation.

Methods : We used Fat1-transgenic mice and their WT littermates and subjected them to mild TBI using left side focal cranial air blast (50-psi) or sham blast (0-psi, control). We conducted visual functional tests, histological, and molecular assays in the brain tissue at 30-days post-blast.

Results : Among different heterogeneous complications, visual function is one of the major sensory parameters affected by TBI. By Optokinetic Nystagmus (OKN) recording, we found that visual acuity decreased, whereas contrast sensitivity increased significantly in WT-blast animals compared to their pre-blast values but not in Fat1-blast animals. By rotarod and open-field studies, we also found Fat1-blast mice were resistant to the declining of motor functions from blast injury. Immunohistochemical labeling of oculomotor nucleus motoneurons for choline acetyltransferase (CHAT) showed a significant reduction in the area of the oculomotor nucleus in WT-blast mice, and immunostaining for IBA1 in the optic tract showed significantly higher numbers of activated microglia of WT-blast mice. Further LC-MS/MS analysis confirmed an elevated level of n-3 PUFA, eicosapentaenoic acid (EPA) in the plasma and brain of the Fat1-transgenic animals. TBI increased Cer level in the brain of the WT mice, which was decreased significantly in the brain of Fat1-blast mice. We further demonstrated that expression of Cer biosynthetic and inflammatory genes was significantly lower in the brain of Fat1-blast mice compared to their WT littermates.

Conclusions : Our result demonstrates that suppression of ceramide biosynthesis and inflammatory factors in Fat1-transgenic animals is associated with significant protection of visual and motor deficits caused by mild TBI.

This is a 2021 ARVO Annual Meeting abstract.

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