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Deficient diet linked to schizophrenia symptoms in mice

11 September 2017
Appeared in BioNews 917

Mice deprived of two essential fatty acids during pregnancy gave birth to pups with schizophrenia-like symptoms, shows a new study.

The pups showed altered expression of genes involved in brain development. The scientists were also able to reverse these epigenetic changes and reduce symptoms using a drug.

'Our work is the first in the field of psychiatry to identify a molecular [mechanism] that links nutritional environment to disease risk,' said first author Dr Motoko Maekawa of the RIKEN Brain Science Institute in Tokyo, Japan.

Schizophrenia is a highly complex disorder that arises from a combination of genetic and environmental factors.  Previous studies have linked two essential fatty acids, omega-3 (DHA) and omega-6 (AA), to schizophrenia. These fatty acids, which can only be obtained from food, are concentrated in the brain and affect its development.

The scientists discovered pregnant mice deprived of DHA and AA produced offspring with schizophrenia-like symptoms, including depression, lower motivation, and impaired memory. When they examined the prefrontal cortex of the schizophrenia-like adult mice, they found reduced expression of genes which code for nuclear receptors, a class of protein important for triggering protein-building in cells. The scientists also discovered reduced expression in genes linked to the GABA (gamma-Aminobutyric acid [γ-Aminobutyric acid]) neurotransmitter, a chemical involved in brain signalling, and in genes linked to oligodendrocyte cells, which help facilitate neuron communication.

When they gave the mice a drug to upregulate the nuclear receptor genes, the oligodendrocyte and GABA genes were also upregulated, and some behaviours were reduced.

'This was evidence that drugs acting on nuclear receptors can be a new therapy for schizophrenia,' said Dr Maekawa.

The researchers also examined hair follicles from two groups of schizophrenia patients, and found reduced expression of the same nuclear receptor genes.

'The next step is to test the effectiveness of drugs that target these nuclear receptors in patients with schizophrenia, and to investigate how nuclear receptors regulate the function of oligodendrocytes and GABAergic neurons to prevent the development of schizophrenic pathophysiology,' said Dr Maekawa.

The study was published in Translational Psychiatry.

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