title: n-3 PUFAs have beneficial effects on anxiety and cognition in female rats: Effects of early life stress.
abstract: Stressful life events, especially those in early life, can exert long-lasting changes in the brain, increasing vulnerability to mental illness especially in females. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a critical role in the development and function of the central nervous system (CNS). Thus, we investigated the influence of an eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) (80% EPA, 20% DHA) n-3 PUFAs mixture on stress-related behavioural and neurobiological responses. Sprague-Dawley female rats were subjected to an early-life stress, maternal separation (MS) procedure from postnatal days 2 to 12. Non-separated (NS) and MS rats were administered saline, EPA/DHA 0.4g/kg/day or EPA/DHA 1g/kg/day, respectively. In adulthood, EPA/DHA treated animals had a dose dependent reduction in anxiety in NS rats. Furthermore, cognitive performance in the novel object recognition task (NOR) was improved by EPA/DHA treatment in NS animals only. EPA/DHA 1g/kg/day decreased behavioural despair in the forced swim test. Notably, EPA/DHA high dose increased the translocation of GRs into the nucleus of NS rat hippocampus. However, the levels of mBDNF remained unchanged in all the experimental groups. The corticosterone response to an acute stress was blunted in MS rats and this was further attenuated by pre-treatment with EPA/DHA. Immune response and monoamine neurotransmission were significantly altered by early-life stress. In conclusion, our study supports the view that n-3 PUFAs are beneficial in neurodevelopmentally normal animals but have little positive benefit in animals exposed to early life stress.
authors.affiliation: Department of Psychiatry, University College Cork, Cork, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. Electronic address: m.pusceddu@ucc.ie.
authors.forename: Matteo M
authors.initials: MM
authors.lastname: Pusceddu
authors.affiliation: Teagasc, Moorepark, Cork, Ireland. Electronic address: phil.kelly@teagasc.ie.
authors.forename: Philip
authors.initials: P
authors.lastname: Kelly
authors.affiliation: Department of Psychiatry, University College Cork, Cork, Ireland. Electronic address: 111123516@umail.ucc.ie.
authors.forename: Nurbazilah
authors.initials: N
authors.lastname: Ariffin
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland. Electronic address: j.cryan@umail.ucc.ie.
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
authors.affiliation: Department of Psychiatry, University College Cork, Cork, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. Electronic address: g.clarke@ucc.ie.
authors.forename: Gerard
authors.initials: G
authors.lastname: Clarke
authors.affiliation: Department of Psychiatry, University College Cork, Cork, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. Electronic address: t.dinan@ucc.ie.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Dinan
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D008426:Maternal Deprivation; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects*; D013315:Stress, Psychological
chemical_list: D015525:Fatty Acids, Omega-3
keywords: Corticosterone; Cytokines; Early life stress; GRs; Monoamine neurotransmitters; n-3 PUFAs