Mental health conditions, including anxiety disorders, autism, and schizophrenia, are significant global health concerns. Researchers at Université de Montréal and the Montreal Clinical Research Institute have made a groundbreaking discovery: a protein complex that plays a crucial role in brain cell connectivity and specific cognitive behaviors. This finding opens up new avenues for potential treatments for anxiety disorders. ()

The new findings, published in The EMBO Journal, could provide valuable therapeutic insights, say researchers led by Hideto Takahashi in collaboration with Steven Connor’s team at York University and Masanori Tachikawa’s team at Japan’s Tokushima University.

The junctions between two brain cells (neurons) are called synapses, which are essential for neuronal signal transmission and brain functions. Defects in excitatory synapses, which activate signal transmission to target neurons, and those in synaptic molecules predispose to many mental illnesses.

Unveiling the Mysteries of Synapse Organization

Although defects in synapse organisation are linked to many neuropsychiatric conditions, the mechanisms responsible for this organisation were poorly understood. Takahashi’s team has previously discovered a new protein complex within the synaptic junction which is only found in excitatory synapses.

The genes coding for these synapses are associated with anxiety disorders and autism, respectively. The work carried out in the new study showed that this particular protein complex regulates the structural and functional maturation of excitatory synapses by regulating the phosphorylation, a biochemical protein modification, of many synaptic proteins, while disruption of this complex causes specific behavioural defects in mice.

High-resolution imaging of the mutant mice brains revealed abnormal synapse organisation, and further study of their signalling properties showed an increase in inactive synapses with defects in signal transmission.

Observing the behaviour of the mutant mice, the scientists saw that they exhibited elevated levels of anxiety, especially enhanced avoidance in unfamiliar conditions, and impaired social behaviours.

Reference:

1. The TrkC-PTPσ complex governs synapse maturation and anxiogenic avoidance via synaptic protein phosphorylation – (https://www.embopress.org/doi/full/10.1038/s44318-024-00252-9)

Source-IANS