Posted on 04/01/2025 5:23:15 PM PDT by Red Badger
Scientists studying mice have uncovered a delicate protein rivalry in the brain that, when thrown off balance, may cause autism-like behaviors.
This discovery opens up a potentially powerful new path for autism treatment by targeting how nerve signals are regulated at the molecular level.
Protein Imbalance Tied to Autism Symptoms
Autism-like symptoms in mice appear when the balance between two key brain proteins is disrupted, according to a study published today (April 1) in PLOS Biology by Dongdong Zhao of Wenzhou Medical University, Yun-wu Zhang of Xiamen University, and their colleagues in China.
Autism Spectrum Disorder (ASD) affects about 1% of the global population and is characterized by challenges in social interaction and cognition. While genetic factors, especially those linked to brain signaling, have been associated with ASD, the exact mechanisms remain unclear. To explore this, the researchers studied two proteins in mice that are thought to play a role in ASD.
Balance Between Two Competing Nerve Proteins Deters Symptoms of Autism
A scheme showing the mechanism underlying MDGA2-mediated944 BDNF/TrkB signaling pathway. Credit: Dongdong Zhao, from Zhao D et al., 2025, PLOS Biology, CC-BY 4.0 (https://creativecommons.org/licenses/by/4.0/)
MDGA2 Mutations and Mouse Behavior
One of these proteins, MDGA2, helps regulate how nerve cells communicate. Mutations in the MDGA2 gene have been found in people with ASD. In this study, mice with reduced levels of MDGA2 showed autism-like behaviors such as repetitive grooming and changes in social behavior. These mice also had increased synaptic activity and elevated levels of BDNF, another brain protein linked to ASD. BDNF affects brain function by binding to a receptor called TrkB.
When the researchers treated the mice with a synthetic peptide that mimics MDGA2 and blocks BDNF/TrkB signaling, the abnormal behaviors were reduced. This suggests that a delicate balance between MDGA2 and BDNF activity is critical for healthy brain function, and its disruption may contribute to ASD-related symptoms.
Restoring Balance with Synthetic Peptides
Based on these results combined with previous research, the authors suggest that MDGA2 and BDNF maintain a natural balance by competing with each other for TrkB protein binding sites, and disruption to this system can lead to regulatory changes in neuron activity related to ASD. This protein system might be a promising target for future therapeutic treatments, but further investigation will be required into the exact functions of this system and its relationship to ASD symptoms.
New Clues in the MDGA2-BDNF Tug-of-War
Yun-wu Zhang adds, “Mutations in the MDGA2 gene cause autism spectrum disorders (ASD) but the underlying mechanism is elusive. Our study reveals a novel role of MDGA2 in keeping the BDNF/TrkB signaling at bay for normal excitatory neuronal activity, and demonstrates that MDGA2 deficiency results in aberrant BDNF/TrkB activation and elevated excitatory neuronal activity, leading to ASD-like phenotypes in mice.”
Citation:
Zhao D, Huo Y, Zheng N, Zhu X, Yang D, Zhou Y, et al. (2025) Mdga2 deficiency leads to an aberrant activation of BDNF/TrkB signaling that underlies autism-relevant synaptic and behavioral changes in mice. PLoS Biol 23(3): e3003047.
https://doi.org/10.1371/journal.pbio.3003047
My wife read this article ten times.
New!
So, where do we get that synthetic peptide?
I’m sure it’ll be on an infomercial real soon.......................
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