Effects of diet on behavioural domains relevant to schizophrenia- a preclinical perspective
Schizophrenia is a psychiatric disorder where onset occurs during adolescence or young adulthood. Poor diet choices may impact on the mental state of schizophrenia patients. For example, a diet high in sugar and polyunsaturated fatty acids can have negative consequences for disease symptoms and outcomes in schizophrenia patients. However, particular diets can have beneficial, therapeutic-like properties for human brain disorders. Finally, dietary choices of mothers have been found to have long-term behavioural and cognitive effects in their offspring. In this thesis, I examined the effect of high fat diet (HFD) in two mutant mouse models for the genetic risk factor neuregulin 1 (NRG1), the transmembrane domain Nrg1 (Nrg1 TM HET) and the Nrg1 type III (Nrg1 III tg) models, and how HFD in a maternal obesity model in C57BL/6J mice can modify schizophrenia-relevant behaviours. HFD increased body weight over time in all mice. Nrg1 TM HET mice exhibited hyper-locomotion and an anxiolytic-like phenotype across sex. Nrg1 TM HET female mice had a less pronounced increase in HFD-induced cue freezing and HFD modulated the response to the cue in a complex genotype-dependent manner. In Nrg1 III tg mice, HFD suppressed locomotion, exploration, and anxiety-related behaviours in a sex-dependent manner. HFD augmented PPI response to increasing prepulse intensities in male mice and decreased pleasure-like seeking behaviour (i.e. sucrose preference) in both female and male mice. HFD had a sex-dependent impact on fear-associated memory with HFD-induced cognitive impairments being most prominent in Nrg1 transgenic females. Finally, offspring of HFD mothers had significantly improved sensorimotor gating compared to offspring of control mothers but showed no altered behavioural response in tests for cognition, sociability, locomotion or exploration. In conclusion, HFD appears to affect behaviours and particular schizophrenia-relevant mutations may play a role in this. The detrimental effects of HFD on particular cognitive domains can be intensified by mutant Nrg1 III in a sex-specific manner. Our data indicate that maternal HFD consumption prior to and during pregnancy and lactation may be beneficial to sensorimotor gating. This indicates the importance to research further the role of diets in the context of populations at risk to develop schizophrenia.
High fat diet, Schizophrenia, Animal models, Neuregulin 1
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