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MONTREAL, October 2024 – Scientists at Université de Montréal and its affiliated Montreal Clinical Research Institute (IRCM) have identified a promising new brain target for the treatment of anxiety disorders. The discovery, published in The EMBO Journal, sheds light on the role of a specific protein complex that influences brain cell connectivity and cognitive behavior, offering potential therapeutic strategies for mental health disorders like anxiety, autism, and schizophrenia.
Led by Hideto Takahashi, in collaboration with Steven Connor from York University and Masanori Tachikawa from Japan’s Tokushima University, the research team explored the role of synapses, the junctions between brain cells, which are critical for neuronal communication and brain function. The study revealed that defects in excitatory synapses, which promote signal transmission to neurons, could predispose individuals to a range of mental illnesses, including anxiety disorders.
Excitatory synapses rely on proper organization to function, but the mechanisms underlying this organization have remained largely unknown. However, Takahashi’s team has uncovered a protein complex within synaptic junctions that is uniquely present in excitatory synapses. The genes coding for these synapses have been linked to anxiety disorders and autism, suggesting that the protein complex plays a key role in regulating synaptic function and cognitive behaviors.
The study’s findings demonstrate that this protein complex is essential for the structural and functional maturation of excitatory synapses. It does this by regulating phosphorylation, a biochemical process that modifies proteins at the synapse. When this complex is disrupted, it leads to specific behavioral defects, as observed in mutant mice used for the study.
High-resolution imaging of the brains of these mutant mice revealed abnormal synapse organization and increased numbers of inactive synapses, which were unable to properly transmit signals. The mice also displayed elevated levels of anxiety, particularly when exposed to unfamiliar environments, and showed impaired social behaviors.
“Our study opens the door to new potential therapeutic strategies for treating anxiety disorders by targeting this protein complex,” said Takahashi. “Understanding the molecular mechanisms behind synapse organization and signal transmission could provide valuable insights into how we can address mental health disorders at their core.”
The research not only offers a deeper understanding of how synaptic defects contribute to anxiety but also paves the way for developing treatments aimed at restoring synapse function in affected individuals.
This breakthrough could bring hope to millions suffering from anxiety disorders and related mental health conditions worldwide, offering a path toward improved therapies that target the brain’s fundamental synaptic processes.
Source: The EMBO Journal
