The Causes of Autism

Who are the spectacular authors, what is the full title of the study, and what year was it published?

Authors: Hongmei Wu, Gang Zhao, Sijin Liu, Quanzhi Zhang, Peng Wang, Yonggang Cao, Lijie Wu.

Title: Supplementation with selenium attenuates autism-like behaviors and improves oxidative stress, inflammation and related gene expression in an autism disease model. Journal of Nutritional Biochemistry 107 (2022) 109034

Year: 2022

What is the study about?

This study explores the potential therapeutic effects of selenium supplementation on autism-like behaviors, oxidative stress, inflammation, and gene expression in a mouse model of autism. The research used BTBR and C57BL/6 (B6) mice as an autism disease model to examine the impacts of sodium selenite treatment on cognitive function, social behavior, repetitive stereotyped behavior, inflammation, oxidative stress, and gene expression in the hippocampus.

What previous research is there on this topic?

Sufficient selenium (Se) levels are crucial for maintaining the cellular redox environment. Increased oxidative stress has been linked to various psychiatric and neurodegenerative disorders, including schizophrenia, depression, Alzheimer’s disease, Parkinson’s disease, and autism, often involving alterations in Se levels. Research suggests that Se supplementation can improve health conditions by reducing inflammation.

In some studies, sodium selenite treatment has been shown to enhance cognitive function in triple transgenic Alzheimer’s disease mice by attenuating lipid peroxidation, and to exhibit antioxidant and anti-inflammatory effects, blocking ferroptosis. Children with ASD were found to have lower serum and hair selenium concentrations than those without ASD, indicating a selenium deficiency.

What methods were used in this study?

On the use of mice in this study: why are BTBR mice appropriate to use for studying autism?

BTBR mice are widely used in autism research due to their stable genotype and consistent display of autism-like behaviors. They exhibit similar social communication disorders and repetitive/stereotyped behaviors to those found in humans with autism spectrum disorders (ASD), and show abnormal brain development and immune biochemical indicators. By studying BTBR mice, researchers can gain valuable insights into the behavioral and genetic mechanisms behind ASD and develop preclinical models to investigate potential treatments for the disorder.

Three Chambered Social Test

The three-chambered social test involved using a clear polycarbonate chamber with a switch gate located in the lower part of the central region. The test was divided into three stages: habituation, sociability, and social preference. To prevent hormonal fluctuations, all experiments were conducted between 9:00 a.m. and 2:00 p.m. During the habituation stage, the mouse being tested was allowed to move freely in the test chamber for 5 minutes. Next, during the sociability stage, an empty metal cage was placed in the right chamber, and a metal cage containing an unfamiliar mouse was placed in the left chamber. The mouse being tested was then placed in the middle chamber and allowed to move freely for 10 minutes to assess its sociability. Finally, during the social preference stage, the positions of the empty metal cage and the metal cage containing the stranger mouse were switched, and an additional unfamiliar mouse was placed in the empty metal cage.

Marble Burying Assay

The marble burying assay is a reliable method for assessing repetitive stereotyped behaviors in mice. This test involves placing a mouse into a standard mouse cage with 5 cm-thick bedding material at the bottom, on which twenty black glass marbles (1 cm diameter) are evenly placed in a 4 x 5 grid. During the 30-minute testing period, the mouse moves freely in the cage. Buried marbles are defined as those with more than 50% coverage by bedding. The test is conducted under dim light (15 lx), and the bedding is replaced between mice. In this study, we employed the marble burying assay to investigate the effects of selenium supplementation on repetitive stereotyped behavior in BTBR and B6 mice.

Morris Water Maze Test

The Morris water maze test is a widely used method for assessing spatial learning and memory in mice. It requires placing a mouse in a circular pool filled with opaque water, and a submerged platform located at a fixed position just beneath the water’s surface. Spatial cues located around the room help the mouse locate the hidden platform. During the place navigation test, the latency period, or the time taken to find the platform, is recorded when the mouse is placed into the first quadrant of the pool. If the mouse fails to locate the platform within 60 seconds, it is guided to the platform and allowed to remain there for 15 seconds. The training is conducted twice a day for four consecutive days, with the environment remaining unchanged. On the fourth day, the platform is removed, and a probe test is conducted to assess the mouse’s memory of the platform’s location. In this study, the effects of selenium supplementation on the learning and memory abilities of BTBR and B6 mice were evaluated using the Morris water maze test.

Other Methods Summarized

The mice were randomly divided into four groups and treated with either sodium selenite solution or saline solution via intraperitoneal injections. After 8 weeks of treatment, the mice were sacrificed and their hippocampi were collected for further analysis. Real-time PCR was used to measure mRNA expression levels of genes related to oxidative stress and inflammation. Nissl staining was performed to quantify neuron loss, and protein expression levels were determined by SDS-PAGE followed by Western blotting. Additionally, commercial assay kits were used to measure the contents of ROS and MDA, as well as the activities of SOD, CAT, and GSH-Px, and levels of GSH in the hippocampal tissue.

What were the findings?

The study found that selenium supplementation significantly ameliorated autism-like behaviors and improved cognitive function in BTBR mice, as well as altered neurotransmitter levels. Specifically, the intervention improved social and cognitive behavior, diminished repetitive stereotyped behavior, and restored the learning and memory abilities of the mice.

Furthermore, the selenium treatment notably boosted SelP protein expression, which controls selenium levels in the brain. The findings also suggest that selenium has a protective effect on the hippocampus by regulating neurotransmitter levels, reducing oxidative stress, alleviating neuroinflammation, and rescuing neural cell damage in autism disease model mice.

What other research is related to these findings?

The findings of this study support previous research indicating the potential therapeutic effects of selenium supplementation on autism-like behaviors. Selenium supplementation has been found to improve certain behaviors in children with autism and enhance spatial learning and memory abilities in mice.

Furthermore, studies have shown that oxidative stress is a significant pathological mechanism in autism, which can result in neural cell damage. The study results suggest that selenium may play a protective role in the hippocampus by regulating neurotransmitter levels, reducing oxidative stress, and alleviating neuroinflammation. This suggests that further research into selenium as a treatment for autism is needed, although more studies are necessary to validate its efficacy and safety in human subjects.

What other studies in the library does this one relate to?

The study by Zhao et al. (2023) found that Selenium levels were positively correlated with gross motor and total scores (TS). This means that lower selenium levels indicate lower gross motor and total scores, while higher selenium levels indicate higher scores. The findings in these two studies correlate with one another.