New Delhi: Mental illnesses like anxiety disorders, autism, and schizophrenia are among the leading health concerns worldwide. Now, scientists report a significant discovery of a new brain target that could open doors for potential treatments of anxiety disorders.
Researchers from Université de Montréal and its affiliated Montreal Clinical Research Institute (IRCM) have identified a unique protein complex that plays a critical role in the functioning of brain cell connections, which are essential for cognitive functions and mental health.
The study is published in The EMBO Journal and was led by Hideto Takahashi in collaboration with Steven Connor’s team at York University and Masanori Tachikawa’s team at Japan’s Tokushima University.
At the core of their research are synapses, which are the junctions between neurons that allow them to communicate. Synapses are vital for transmitting signals in the brain, and defects in these connections—specifically in excitatory synapses that activate signal transmission—are linked to numerous mental illnesses.
The researchers focused on a particular protein complex that is only found in excitatory synapses. Their previous work had already connected the genes coding for this complex to anxiety disorders and autism. However, until now, the mechanisms by which this complex influences synapse organization and function were not well understood.
In this new study, Takahashi’s team discovered that the protein complex regulates the structural and functional maturation of excitatory synapses through a process called phosphorylation, a biochemical modification that impacts various synaptic proteins.
This regulation is crucial for the proper formation and function of synapses. When this protein complex was disrupted in mutant mice, it led to disorganized synapses, a significant increase in inactive synapses, and impaired signal transmission across neurons.
Using advanced high-resolution imaging, the scientists observed striking abnormalities in the synapse organization of the mutant mice. These defects were strongly linked to changes in behaviour, as the mutant mice exhibited higher levels of anxiety.
Specifically, the mice demonstrated enhanced avoidance behaviour in unfamiliar situations, a key marker of anxiety, and also showed signs of impaired social interaction, which aligns with behaviours seen in human anxiety and autism spectrum disorders.
“Our study sheds light on how synaptic dysfunction at the molecular level can lead to complex behavioural disorders like anxiety,” said lead researcher Hideto Takahashi. “We believe targeting this protein complex could open up new avenues for therapeutic interventions aimed at treating anxiety and other related conditions.”
The findings are particularly relevant because the defective synapses caused by this protein complex are linked to neurodevelopmental and neuropsychiatric disorders, providing deeper insights into how disruptions at the cellular level can lead to cognitive and social deficits.
“This discovery is exciting because it not only helps us understand the mechanisms of mental illness but also points toward potential new treatments,” added Steven Connor, a collaborator from York University.
Future studies are planned to explore how modulating the activity of this protein complex might help restore normal synapse function and potentially reverse anxiety-related behaviors. If successful, this research could lay the groundwork for developing drugs or other therapeutic approaches aimed at treating mental illnesses linked to synaptic defects.