Omega-3 fatty acids during adolescence prevent schizophrenia-related behavioural deficits: Neurophysiological evidences from the prenatal viral infection with PolyI:C Articles uri icon

authors

  • CASQUERO VEIGA, MARTA
  • Leza, Juan C.
  • Arango, Celso
  • DESCO MENENDEZ, MANUEL
  • SOTO MONTENEGRO, Mª LUISA
  • Romero Miguel, Diego
  • MacDowell, Karina S.
  • Torres Sanchez, Sonia
  • Garcia Partida, Jose Antonio
  • LAMANNA RAMA, NICOLÁS
  • GOMEZ RANGEL, VANESSA
  • ROMERO MIRANDA, ANA
  • Berrocoso, Esther

publication date

  • May 2021

start page

  • 14

end page

  • 27

volume

  • 46

International Standard Serial Number (ISSN)

  • 0924-977X

Electronic International Standard Serial Number (EISSN)

  • 1873-7862

abstract

  • The likely involvement of inflammation and oxidative stress (IOS) in mental disease has led to
    advocate anti-oxidant and anti-inflammatory drugs as therapeutic strategies in the treatment
    of schizophrenia. Since omega-3 fatty acids ( ω-3) show anti-inflammatory/neuroprotective
    properties, we aim to evaluate whether ω-3 treatment during adolescence in the maternal immune
    stimulation (MIS) animal model of schizophrenia could prevent the brain and behavioural
    deficits described in adulthood. At gestational day 15, PolyI:C (4 mg/kg) or saline (VH) were
    injected to pregnant Wistar rats. Male offspring received ω-3 (800 mg/kg) or saline (Sal) daily
    from postnatal day (PND) 35–49, defining 4 groups: MIS- ω-3; MIS-Sal; VH- ω-3 and VH-Sal. At
    PND70, rats were submitted to prepulse inhibition test (PPI). FDG-PET and T2-weighted MRI
    brain studies were performed in adulthood and analyzed by means of SPM12. IOS markers
    were measured in selected brain areas. MIS-offspring showed a PPI deficit compared with VHoffspring
    and ω-3 treatment prevented this deficit. Also, ω-3 reduced the brain metabolism
    in the deep mesencephalic area and prevented the volumetric abnormalities in the hippocampus
    but not in the ventricles in MIS-offspring. Besides, ω-3 reduced the expression of iNOS
    and Keap1 and increased the activity/concentration of HO1, NQO1 and GPX. Our study demonstrates
    that administration of ω-3 during adolescence prevents PPI behavioural deficits and
    hippocampal volumetric abnormalities, and partially counteracts IOS deficits via iNOS and Nrf2–
    ARE pathways in the MIS model. This study highlights the need for novel strategies based on
    anti-inflammatory/anti-oxidant compounds to alter the disease course in high-risk populations
    at early stages.

keywords

  • fdg-pet/resonance; inflammation/oxidative stress; mental health prevention; omega-3 fatty acids; polyi:c model of schizophrenia