Basic researchers at the Université de Montréal and its affiliated IRCM found that a particular protein complex is involved in the structural architecture of Brain cells’ connectivities and in some responsive behaviours.
The research by a team led by Hideto Takahashi, director of the IRCM’s synapse development and plasticity research unit in collaboration with the teams of Steven Connor at York University and Masanori Tachikawa at Japan’s Tokushima University is published in The EMBO JournalAnother thing that should be noted in this work is that two objectives are relevant to recall with this research, said Takahashi, who is an associate
“One is to identify new modality of signal transduction amongst brain cells,” he said. The other is to generate a new genetically modified unique animal model of anxiety disorders with panic disorder- and agoraphobia-like phenotypes, which is useful for the development of new therapeutics.
The space connection between two neurons is called synapse being critical to neuronal signal and brain activity. It is hypothesised that the function of excitatory synapses, which trigger signal initiation to target neurons and or abnormalities of distinct synaptic molecules, favour multiple mental illnesses.
Takahashi’s team has earlier identified a new protein complex in the synaptic junction, specific to excitatory synapse, the TrkC-PTPσ. TrkC (NTRK3) is known to be related to anxiety disorders and PTPσ (PTPRS) with autism.
The work done by us in the novel study by the first author, Husam Khaled, a doctoral student in the laboratory of Dr Takahashi, demonstrated that the TrkC-PTPσ complex contributes to the structural and functional development of excitatory synapses through governing multiple aspects of phosphorylation of various synaptic proteins but not development of excitatory synapses itself, disruption of the complex leads to certain behavioural alteration in mice.
Building blocks of the brain
Neurons surrounding each other are connected by synapses that are similar to gates and provide access to the exchange of the signals between them.
Damage to synapses or any of their parts can interfere with neuron interaction, and thus cause several diseases of the brain.
This way, by obtaining mice with specific genetic changes that affect the TrkC-PTPσ complex, Takahashi’s team discovered the special roles of this complex. They showed that this complex controls the phosphorylation of many proteins associated with synapse morphology and positioning.
Histopathological analysis of the brains from the mutant mice elucidated aberrant organisation of synapses in the brain tissue; subsequent investigations of signalling characteristic of the affected synapses demonstrated the presence of an exaggerated proportion of ineffective synapses with impaired signal conduction.
Watching how the behaviour of mutant mice changed, the scientific team noticed that they have increased anxiety level, advancing avoidance in new conditions and impaired social interactions.
Reference:
Montreal U of. Brain cell connectivity research provides a potential target for anxiety disorders
