Role of polyunsaturated fatty acids in murine emotional behavior

Abstracts / Neuroscience Research 71S (2011) e6–e44

been characterizing proteins, peptides and small molecules that recognize specific lipids or specific lipid organization. Recently we have introduced the combination of freeze-fracture replica technique with immunocytochemical labeling. With this method, one can examine lateral and transmembrane lipid distribution in biomembranes under electron microscope. Our recent attempts to visualize lipid domains will be summarized. Research fund: KAKENHI (22390018). doi:10.1016/j.neures.2011.07.122

S3-E-1-2 Role of polyunsaturated fatty acids in murine emotional behavior Toru Moriguchi Department of Food and Life Sci., Azabu University, Sagamihara, Japan The n-3 polyunsaturated fatty acids, which cannot be synthesized in mammals, are the major long-chain polyunsaturated fatty acids. Docosahexaenoic acid (DHA, 22:6n-3) of the n-3 fatty acid family is specifically concentrated in the brain and retina, and are deposited mostly during the perinatal and early postnatal period, which is the brain and retinal development. DHA exists mainly in the form of membrane phospholipids, which are known to be crucial for maintaining normal brain structure and function. These suggest that the n-3 fatty acids assume an extremely important role in the nervous system. Several rodent studies have reported that lower DHA levels in the brain led to poorer performance on a variety of cognitive, learning and memory such as olfactory discrimination and spatial learning tasks. Also, it has recently been well documented that animal model of dietary n-3 fatty acids deprivation exhibit the enhancement of anxiety in the emotional behavior using the elevated plus maze and the novelty suppressed feeding paradigm, compared with the n-3 fatty acid adequate mice. Moreover, epidemiological studies of healthy people and postpartum women indicate a negative correlation between dietary n-3 fatty acids intake and mental illness including serious mood disorders, aggression, depression, and bipolar disorder. These findings suggest that mental illness may be associated with reduced dietary intake of the n-3 fatty acids. In this symposium, I will present the change in the emotional behavior as a brain function in the n-3 polyunsaturated fatty acids deficient mice, and discussed the relation between the fatty acid composition and the sensitivity of the chronic mild stress. doi:10.1016/j.neures.2011.07.123

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Research fund: Grant-in-Aid for Young Scientists (B): 21791156. doi:10.1016/j.neures.2011.07.124

S3-E-1-4 Fish consumption and psychophysiological activities during mental stress Kenta Matsumura 1,2 , Takehiro Yamakoshi 3 , Hiroko Noguchi 1,4 , Yutaka Matsuoka 1,5 1 Department of Adult Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan 2 School of Mechanical Engineering, College of Science and Engineering, Kanazawa University, Kanazawa, Japan 3 Graduate School of Natural Science & Technology, Kanazawa University, Kanazawa, Japan 4 Clinical Psycology Center, Musashino University, Tokyo, Japan 5 Department of Psychiatry and Clinical Research Institute, National Disaster Medical Center, Tokyo, Japan

Objective: Human studies have shown that habitual fish consumption protects against coronary heart disease (CHD). Recent studies on cardiovascular function and hemodynamics have elucidated the mechanisms underlying this cardioprotective effect. However, to our knowledge, no study has examined the effect of frequent fish consumption on acute mental stress responses. Accordingly, we examined whether fish eaters (individuals eating baked fish more than 3–4 times/week) show less cardiovascular responses during mental stress than controls (individuals eating fish less than 1–2 times/week). Methods: Ffish eaters (10 women and 2 men, 21.4 ± 3.7 years) and controls (11 women and 2 men, 21.9 ± 3.1 years) performed mental arithmetic (MA) and mirror-tracing (MT) tasks during which cardiovascular indices, including heart rate (HR), pre-ejection period (PEP), blood pressure (MBP), baroreflex sensitivity (BRS), and pulse wave velocity (PWV), were measured and compared with the baseline (BS) values. Results and discussion: A series of separate 2-way mixed-design ANOVAs revealed that HR, BP, and PWV were significantly lower, and PEP and BRS were significantly higher in the fish eaters than in the controls during rest and while performing MA and MT tasks. No significant interactions were observed. This indicates that the protective effects of eating fish are reflected in cardiovascular activity and not responses. Reduction in cardiovascular activities and arterial stiffness in fish eaters may be a mechanism by which fish eaters show a lower prevalence of CHD. Research fund: KAKENHI22700707 and JST, CREST. doi:10.1016/j.neures.2011.07.125

S3-E-1-3 Lack of long-chain polyunsaturated fatty acids during developmental stage may increase the risk of schizophrenia

S3-E-1-5 Psychiatric disorders and polyunsaturated fatty acids—What have we learnt from epidemiological studies?

Motoko Maekawa 1 , Kei Hamazaki 2 , Takeo Yoshikawa 1

Kei Hamazaki 1 , Hidekuni Inadera 1 , Tomohito Hamazaki 2

1

1 Department of Public Health, Faculty of Medicine, University of Toyama, Toyama, Japan 2 Department of Clinical Sciences, Institute of Natural Medicine, University of Toyama, Toyama, Japan

RIKEN, Brain Science Institute, Laboratory for Molecular Psychiatry 2 Department of Public Health, Faculty of Madicine, University of Toyama In our previous study, we performed a quantitative trait loci analysis using mice, to search for prepulse inhibition (PPI)-regulating genes, whose impairments are reported to be across mental disorders including schizophrenia. Consequently, we identified the fatty acid binding protein 7 (Fabp7) gene. Fabp7 knockout mice displayed decreased PPI and other schizophrenia-like behavioral phenotypes. We also showed that human FABP7 is associated with schizophrenia in males and with bipolar disorder. Fabp genes have the following features: (i) they encode small 14-15 kDa intra-cellular proteins, (ii) they exist across species, from flies to mice and humans with strong phylogenetic conservation, (iii) they are thought to be intracellular lipid chaperons, (iv) their ligands are reported to be polyunsaturated fatty acids (PUFAs). Lipid abnormalities have been reported in patients with mental disorders across diagnostic categories. In addition, we have recently reported that PUFAs improve PPI in rats. In the current study, we firstly showed that Fabp7 is expressed in cortex, hippocampus and nucleus accumbence in adult mice. Moreover, approximately 90% of Fabp7(+) cells are NG2(+) cells, oligodendrocyte progenitors, which receive GABAergic inputs. Secondly, to see the effects of intake of essential fatty acids (arachidonic acid; ARA and docosahexaenoic acid; DHA) during development, in the adult brain, we prepared mice that were raised with deficient or rich those essential fatty acid diet. We observed altered neural activities in the several brain regions between (ARA and DHA)-deficient mice and (ARA and DHA)-rich mice detected by manganese-enhanced MRI. In addition, we found that broad downregulation of genes related to oligodendrocyte and GABAergic systems, which conforms to a current theory of schizophrenia and bipolar disorders. These results proposed that the detailed analyses of NG2(+)/Fabp7(+) cells are warranted to decipher the pathophysiology of mental illnesses.

Background: We have previously investigated n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in the postmortem hippocampus from subjects with schizophrenia and bipolar disorder, and controls; however, we found no significant differences except for small ones in n-6 LCPUFAs (Hamazaki et al., J. Psychiatr. Res., 2010). Other studies with postmortem orbitofrontal cortex showed abnormalities in n-3 LCPUFAs in individuals with schizophrenia and major depression. In the present study we investigated whether there were any abnormalities in LCPUFAs in the amygdala of schizophrenia, bipolar disorder and major depression compared to unaffected controls. Methods: We obtained from the Stanley Medical Research Institute 15 amygdala samples each for schizophrenia, bipolar disorder, major depression and controls matched for age and sex. Amygdala tissues were scraped off from 3 consecutive frozen sections for microscopic slides (14 ␮m each) and homogenized. Total lipids were extracted and total phospholipid fractions were separated by thin-layer chromatography. The fatty acid composition was analyzed by gas chromatography. Results: Unlike the previous studies with the orbitofrontal cortex and hippocampus, we found no significant differences in major LCPUFAs. The amounts of docosahexaenoic acid (%), the major n-3 LCPUFA, were 10.0 ± 0.3, 10.0 ± 0.3, 9.3 ± 0.3 and 9.7 ± 0.3 in schizophrenia, bipolar disorder, major depression and unaffected controls, respectively. The composition of arachidonic acid (%), the major n-6 LCPUFA, was 9.0 ± 0.2, 9.2 ± 0.1, 9.4 ± 0.2 and 9.4 ± 0.2 respectively. Conclusions: Changes in LCPUFAs in these psychiatric disorders may be specific to certain brain regions. LCPUFAs in the amygdala may not be the etiology of these diseases. Research fund: Polyene Project Corp. doi:10.1016/j.neures.2011.07.126