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

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 VH-offspring 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.

subjects

  • Biology and Biomedicine
  • Psychology

keywords

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