A significant breakthrough in the search for the potential root causes of bipolar disorder has been made by researchers at Ulsan National Institute of Science and Technology in South Korea.
The study suggests the cellular protein phospholipase Cγ1 (PLCγ1) could be a new promising candidate gene for bipolar disorder.
The findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior. This breakthrough is expected to be widely used in research for the treatment of the manic symptoms associated with bipolar disorder.
PLCγ1 has been proposed as a candidate gene for bipolar disorder in previous studies. However, it has been unclear that how the PLCγ1 plays a role in neron-to-neuron signaling and how it is related to mental illnesses, like bipolar disorder.
The research team, led by Professor Pann-Ghill Suh of Life Sciences at Ulsan National Institute of Science and Technology (UNIST), created forebrain-specific PLCγ1-deficient mice and observed what happened in brain synapses of this mouse. The researchers reported that mice with forebrain-selective deletion of PLCγ1 also exhibit manic-like behavior, as well as deficits in inhibitory transmission and BDNF-dependent synaptic plasticity.
These symptoms were alleviated after the drug treatment for bipolar disorder was given.
“In the brain, excitatory synapses and inhibitory synapses work together to remain balanced for proper neurotransmission,” says Professor Suh. “Our study demonstrated that the imbalance between these two is a major cause of various neuropsychiatric disorders and the GABAergic dysfunction observed in the hippocampi of bipolar disorder patients."
According to the research team, the inhibitory synapses that lacks PLCγ1 protein do not work properly in excitatory neurons.
This is due to the improper signaling of BDNF, which is critical for the synapse formation. This leads to an imbalance of excitatory synapses and inhibitory synapses, and causes mental illnesses, like bipolar disorder.
“After 10 years of research, we have finally revealed PLCγ1 protein plays a major role in the onset of bipolar disorder,” says Professor Suh. “Our findings, therefore, provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior."
The finding is expected to have an impact on research into the treatment of bipolar disorder.
Y R Yang et al Forebrain-specific ablation of phospholipase Cγ1 causes manic-like behavior Molecular Psychiatry (2017). DOI: 10.1038/mp.2016.261