Summary: Researchers have made a major advance, discovering that a low-dose mixture of zinc, serine, and branch-chain amino acids (BCAAs) can successfully alleviate behavioral symptoms in three different mouse models of autism. This breakthrough lies in the synergy of the three common nutrients, which work together to restore normal neural communication and reduce hyperactivity in the brain’s emotional center.
Crucially, giving the supplements individually at the same low doses had no effect, proving the power of the combination therapy. This finding offers a safer, highly practical, nutrient-based strategy for long-term ASD support that may eventually be applicable to children.
Key Facts
- Synergy is Key: The successful treatment hinges on the combined effect of low-doses of zinc, serine, and BCAAs; giving the nutrients individually was ineffective.
- Brain Reset: The mixture restored synaptic protein expression and reduced abnormal amygdala hyperactivity, the region of the brain involved in emotional and social processing.
- Broad Potential: The treatment worked in three distinct genetic mouse models of ASD, suggesting it could be a broadly applicable strategy rather than a niche, gene-specific therapy.
Source: PLOS
Researchers led by Tzyy-Nan Huang and Ming-Hui Lin from Academia Sinica in Taiwan report that a low-dose mixture of zinc, serine, and branch-chain amino acids can alleviate behavioral deficits in three different mouse models of autism.
Published December 2nd in the open-access journal in PLOS Biology, the study shows that when combined together, these three dietary supplements promote communication between neurons in the brain and improve social behaviors.
Autism spectrum disorder (ASD) is known to result from abnormal neural development that affects how neurons are connected. At the same time, nutrition is known to be one of the environmental factors that influences ASD.
Individually, zinc, serine, and branch-chain amino acids are all thought to have positive effects on neural connectivity. The authors hypothesized that a mixture of the three would be a more effective treatment than any individually and that the necessary dosages of each could be lowered.
They tested their theory in three mouse models of ASD; they measured amounts of synapse-related proteins, used calcium imaging to examine neural activity in the amygdala and assessed social behavior.
The researchers found that the cocktail of supplements altered the brains of autistic mice so that the expression of proteins in the synapse resembled those of normal mice and that the abnormal hyperactivity of neurons in the amygdala was reduced after taking the cocktail. The researchers also found that social behaviors in the animals improved after they were given the cocktail.
However, when each supplement was given separately, the same dosages had no effect on behavior. This was true in two additional mouse models of autism, showing that it’s the synergistic effect of combining the three supplements that allows it to be effective at low doses.
Yi-Ping Hsueh summarized, “As hundreds of genes are implicated in autism, each with distinct molecular functions, a ‘one gene–one therapy’ approach is impractical for addressing the complexity of ASD.
“Our findings show that a low-dose nutrient mixture containing zinc, branched-chain amino acids (BCAAs), and serine—working synergistically to improve synaptic function and social behaviors across three ASD mouse models—offers a safer and more practical strategy for long-term, broad application, even beginning in childhood.”
Tzyy-Nan Huang, one of the study’s first authors, emphasized, “High doses of individual nutrient supplements such as zinc, branched-chain amino acids, and serine can improve synaptic function through different mechanisms, but low doses of any single nutrient alone are ineffective. It is exciting to see that combining these nutrients at low doses successfully restores synaptic proteomes and enhances social behaviors in three different mouse models of autism.”
Ming-Hui Lin, the study’s co–first author, added, “I was thrilled to observe that just seven days of treatment with the nutrient mixture significantly modulated neuronal circuit activity and connectivity in real time. These results provide strong support for the beneficial effects of low-dose nutrient supplement combinations.”
Funding: This work was supported by grants from Academia Sinica, Taiwan (AS-IA-111-L01 to Y.-P.H.) and the National Science and Technology Council, Taiwan (NSTC 113-2326-B-001-008 and 114-2326-B-001-005 to Y.-P.H.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Key Questions Answered:
A: Researchers found that a low-dose, synergistic mixture of zinc, serine, and branch-chain amino acids (BCAAs) successfully improved social behaviors and neural communication in three different mouse models of Autism Spectrum Disorder (ASD). The treatment relies on the combination; individual nutrients at the same low doses were ineffective.
A: The cocktail works by restoring key biological functions in the brain. Specifically, it corrected the expression of synaptic proteins (which neurons use to communicate) and significantly reduced abnormal hyperactivity in the amygdala, a brain region critical for social behavior and emotional processing.
A: The mixture is a breakthrough because it offers a safer, practical, and broadly applicable strategy that targets a common functional deficit (synaptic dysfunction) across multiple ASD models. This contrasts with the difficulty of the “one gene–one therapy” approach, making it promising for widespread long-term use, potentially starting in childhood.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this Autism research news
Author: Claire Turner
Source: PLOS
Contact: Claire Turner – PLOS
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Low-dose mixtures of dietary nutrients ameliorate behavioral deficits in multiple mouse models of autism” by Yi-Ping Hsueh et al. PLOS Biology
Abstract
Low-dose mixtures of dietary nutrients ameliorate behavioral deficits in multiple mouse models of autism
Autism spectrum disorder (ASD) is a group of heterogeneous, behaviorally defined neurodevelopmental conditions influenced by both genetic and environmental factors.
Here, we show that supplementation of multiple low-dose nutrients—an important environmental factor contributing to ASD—can modulate synaptic proteomes, reconfigure neural ensembles, and improve social behaviors in mice.
First, we used Tbr1+/− mice, a well-established model of ASD, to investigate the effect of nutrient cocktails containing zinc, branched-chain amino acids (BCAA), and serine, all of which are known to regulate synapse formation and activity. Supplementation of nutrient cocktails for 7 days altered total proteomes by increasing synapse-related proteins.
Our results further reveal that Tbr1 haploinsufficiency promotes hyperactivation and hyperconnectivity of basolateral amygdala (BLA) neurons, enhancing the activity correlation between individual neurons and their corresponding ensembles.
Nutrient supplementation normalized the activity and connectivity of the BLA neurons in Tbr1+/− mice during social interactions.
We further show that although a low dose of individual nutrients did not alter social behaviors, treatment with supplement mixtures containing low-dose individual nutrients improved social behaviors and associative memory of Tbr1+/− mice, implying a synergistic effect of combining low-dose zinc, BCAA, and serine. Moreover, the supplement cocktails also improved social behaviors in Nf1+/− and Cttnbp2+/M120I mice, two additional ASD mouse models.
Thus, our findings reveal aberrant neural connectivity in the BLA of Tbr1+/− mice and indicate that dietary supplementation with zinc, BCAA, and/or serine offers a safe and accessible approach to mitigate neural connectivity and social behaviors across multiple ASD models.
