Doesn’t an Excessive Intake of Simple Sugar Affect Higher Brain Function?

Summary: A new study in mice found excessive sugar intake during puberty could be an environmental risk factor for the development of psychiatric disorders in those with genetic predispositions.

Source: TMIMS

There has been a remarkable increase in intake of simple sugar (sucrose, isomerized sugar (corn syrup) from beverages and diets in modern society. The intake of simple sugars in adolescents, in whom mental disorders frequently occur, is higher than any other generations. Moreover, patients with mental disorders consume approximately 2-fold more sugar than age-matched healthy individuals, and patients with schizophrenia who consume more sucrose exhibit more severe symptoms.

Despite accumulating evidence, it is still unproven that excessive sugar intake contributes to the pathogenesis of psychiatric disorders among susceptible individuals. Doesn’t an excessive intake of simple sugar affect higher brain function? Researchers have attempted to elucidate this causal relationship.

As a susceptibility gene for psychiatric disorder, the researchers selected Glyoxylase-1 and Disrupted-in-schizophrenia-1. By combining the heterozygous mice with environmental factors of excessive sugar intake at the age of puberty, they successfully created a novel mouse model exhibiting various mental disorder-like symptoms, including decreased sensorimotor gating function, decreased working memory, hyperactivity, abnormal gamma-band component in EEG.

In other words, this demonstrates a possibility that the excessive intake of simple sugar at the age of puberty could be an environmental risk factor of psychiatric disorders.

Furthermore, by analyzing this model mouse, the team aimed to identify the new phenotypes and mechanisms of developing mental disorders. They found “cerebral microvascular angiopathy.”

This is a diagram from the study
Excessive sucrose intake during adolescence cause cellular damage in non-neuronal cell groups, inhibiting the uptake of glucose from the blood into the brain parenchyma, leading to dysfunctions of certain neurons that cause the major symptoms of psychiatric disorders. Credit: TMIMS

In order to verify the generality of this finding, they used a post-mortem brain from patients with schizophrenia and bipolar disorder and identified angiopathy similar to the one seen in the model mice. They also found that the angiopathy was accompanied by impaired glucose incorporation to brain parenchyma in their mice model.

These phenotypes were prevented by continuous administration of non-steroidal anti-inflammatory drugs (NSAIDs) before the onset of the disease, and some psychiatric-like symptoms were also suppressed. Notably, the patients used in this study did not necessarily have a record of excessive sucrose intake.

They developed psychiatric disorders under various stress circumstances, suggesting that psychiatric disorders are associated with angiopathy in the brain caused by various environmental stresses, including metabolic stress.

About this neuroscience research news

Author: Press Office
Source: TMIMS
Contact: Press Office – TMIMS
Image: The image is credited to TMIMS

Original Research: Open access.
High-sucrose diets contribute to brain angiopathy with impaired glucose uptake and psychosis-related higher brain dysfunctions in mice” by Shinobu Hirai et al. Science Advances


Abstract

High-sucrose diets contribute to brain angiopathy with impaired glucose uptake and psychosis-related higher brain dysfunctions in mice

Metabolic dysfunction is thought to contribute to the severity of psychiatric disorders; however, it has been unclear whether current high–simple sugar diets contribute to pathogenesis of these diseases.

Here, we demonstrate that a high-sucrose diet during adolescence induces psychosis-related behavioral endophenotypes, including hyperactivity, poor working memory, impaired sensory gating, and disrupted interneuron function in mice deficient for glyoxalase-1 (GLO1), an enzyme involved in detoxification of sucrose metabolites.

Furthermore, the high-sucrose diet induced microcapillary impairments and reduced brain glucose uptake in brains of Glo1-deficient mice. Aspirin protected against this angiopathy, enhancing brain glucose uptake and preventing abnormal behavioral phenotypes.

Similar vascular damage to our model mice was found in the brains of randomly collected schizophrenia and bipolar disorder patients, suggesting that psychiatric disorders are associated with angiopathy in the brain caused by various environmental stresses, including metabolic stress.

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