title: Dietary supplementation with n-3 fatty acids from weaning limits brain biochemistry and behavioural changes elicited by prenatal exposure to maternal inflammation in the mouse model.
abstract: Prenatal exposure to maternal immune activation (MIA) increases the risk of schizophrenia and autism in the offspring. The MIA rodent model provides a valuable tool to directly test the postnatal consequences of exposure to an early inflammatory insult; and examine novel preventative strategies. Here we tested the hypotheses that behavioural differences in the MIA mouse model are accompanied by in vivo and ex vivo alterations in brain biochemistry; and that these can be prevented by a post-weaning diet enriched with n-3 polyunsaturated fatty acid (PUFA). The viral analogue PolyI:C (POL) or saline (SAL) was administered to pregnant mice on gestation day 9. Half the resulting male offspring (POL=21; SAL=17) were weaned onto a conventional lab diet (n-6 PUFA); half were weaned onto n-3 PUFA-enriched diet. In vivo magnetic resonance spectroscopy measures were acquired prior to behavioural tests; glutamic acid decarboxylase 67 (GAD67) and tyrosine hydroxylase protein levels were measured ex vivo. The main findings were: (i) Adult MIA-exposed mice fed a standard diet had greater N-acetylaspartate/creatine (Cr) and lower myo-inositol/Cr levels in the cingulate cortex in vivo. (ii) The extent of these metabolite differences was correlated with impairment in prepulse inhibition. (iii) MIA-exposed mice on the control diet also had higher levels of anxiety and altered levels of GAD67 ex vivo. (iv) An n-3 PUFA diet prevented all the in vivo and ex vivo effects of MIA observed. Thus, n-3 PUFA dietary enrichment from early life may offer a relatively safe and non-toxic approach to limit the otherwise persistent behavioural and biochemical consequences of prenatal exposure to inflammation. This result may have translational importance.
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong, China.|State Key Laboratory for Cognitive and Brain Sciences, The University of Hong Kong, Hong Kong, China.|HKU-SIRI, The University of Hong Kong, Hong Kong, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong, China.
authors.forename: Y O
authors.initials: YO
authors.lastname: Leung
authors.affiliation: Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong, China.|Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China.
authors.forename: I
authors.initials: I
authors.lastname: Zhou
authors.affiliation: Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong, China.|Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China.
authors.forename: L C
authors.initials: LC
authors.lastname: Ho
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong, China.
authors.forename: W
authors.initials: W
authors.lastname: Kong
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: P
authors.initials: P
authors.lastname: Basil
authors.affiliation: Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: R
authors.initials: R
authors.lastname: Wei
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong, China.
authors.forename: S
authors.initials: S
authors.lastname: Lam
authors.affiliation: Department of Neurology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong, China.
authors.forename: A C K
authors.initials: AC
authors.lastname: Law
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong, China.
authors.forename: S E
authors.initials: SE
authors.lastname: Chua
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong, China.|State Key Laboratory for Cognitive and Brain Sciences, The University of Hong Kong, Hong Kong, China.|Centre for Reproduction, Development and Growth, The University of Hong Kong, Hong Kong, China.|Genome Research Centre, The University of Hong Kong, Hong Kong, China.
authors.forename: P C
authors.initials: PC
authors.lastname: Sham
authors.affiliation: Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong, China.|Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China.
authors.forename: E X
authors.initials: EX
authors.lastname: Wu
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong, China.|Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK.
authors.forename: G M
authors.initials: GM
authors.lastname: McAlonan
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D003401:Creatine / Q000378:metabolism; D059305:Diet, High-Fat / Q000379:methods; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000276:immunology*; D007294:Inositol / Q000378:metabolism; D008297:Male; D051379:Mice; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology / Q000517:prevention & control; D065808:Prepulse Inhibition / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D014886:Weaning
chemical_list: D015525:Fatty Acids, Omega-3; D020011:Protective Agents; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine