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Transl Psychiatry. 2015 Sep 22;5:e641. doi: 10.1038/tp.2015.126.

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.

Li Q1,2,3, Leung YO1, Zhou I4,5, Ho LC4,5, Kong W1, Basil P6, Wei R7, Lam S1, Zhang X8, Law AC1, Chua SE1, Sham PC1,2,9,10, Wu EX4,5, McAlonan GM1,11.

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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.
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.
Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China.
Department of Neurology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 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.
Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK.


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.

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