Maternal diet causes excess of endocannabinoids impacting foetal brain

Maternal diet causes excess endocannabinoids impacting foetal brain
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A new study has shown that high-fat maternal diets can cause life-long changes in the brain of unborn offspring.

A team from MedUni Vienna’s Center for Brain Research has found that maternal diets high in polyunsaturated omega-6 fatty acids leads to the production of excess endocannabinoids.

This overloads the foetus and can impair the development of healthy brain networks which is said by the researchers to be relevant to pathologies such as ADHD, schizophrenia and anxiety disorders.

The study, which has been published in the journal Molecular Psychiatry, examined in cell- and mouse models, how intake of high-fat diets throughout pregnancy impacts foetal brain development.

Excess endocannabinoids

When the mother consumes a high-fat diet during pregnancy, both mother and child produce excess endocannabinoids, which can even be transferred from the mother to the foetus.

Endocannabinoids can then overload the corresponding cannabinoid receptors in the foetal brain and limit their ability to signal. As a result, nerve cells will no longer be able to correctly integrate into the brain to fulfil their prospective functions.

The study also shows that these impairments persist throughout life of the affected offspring and can serve as critical triggers to developing psychiatric disorders later in life.

What are endocannabinoids?

Endocannabinoids are substances produced by the body itself. They are part of the endocannabinoid system (ECS), which serves as a fundamental communication system in the brain as well as other organs.

In the adult brain, endocannabinoids limit communication (‘chemical neurotransmission’) between neurons by binding to cannabinoid receptors. In the developing brain, endocannabinoids determine when and where neurons are positioned and if they form connections with each other. This means that any substance that influences either endocannabinoid levels or directly affects cannabinoid receptor function will inevitably impinge upon brain development.

Principal investigator Tibor Harkany, Head of the Department of Molecular Neurobiology at MedUni Vienna’s Center for Brain Research, said:  “By acting like a ‘stop signal’, a prolonged overload of endocannabinoids impairs the developmental programme of many neurons in the foetal brain.

“Persistently muting cannabinoid receptors, we believe, alters the epigenetic programs of affected nerve cells. Epigenetic mechanisms determine the pattern of gene expression in any cell. If damaged, the cells are no longer able to carry out their functions adequately.

“This will limit their ability to adapt their proper shape or select communication partners because of a shortage of proteins required as cellular building blocks or signalling molecules.”

On a large scale, an inhibition to the creation of connections between brain cells will impair the formation of important neuronal networks, the functional building blocks of the brain. This can result in said psychiatric disorders such as ADHD, schizophrenia and anxiety disorders.

Irreversible damage

Harkany said: “As far as we can tell, the pathological changes of nerve cells we have found are irreversible.

“It is of limited use, changing to a healthy, low-fat diet after birth when the damage has already been done.”

Although the study is based on animal models, Harkany stresses that other studies already indicate harmful effects in humans, while this report identifies the very molecular mechanisms that can also apply to humans.

Lead author, Valentina Cinquina, said: “In order to find effective treatments, we will need active agents that directly intervene in the epigenetic regulation of gene expression.

“We have not yet trialled any such drugs but it is an exciting prospect to work on such interventions, which can perhaps be used safely and effectively in the future.”

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