Researchers Validate Bipolar Candidate Gene In Mice

Researchers have shown that mice without the gene for PLCγ1 in their forebrains exhibit manic-like behaviors.

AsianScientist (Feb. 22, 2017) – In a study published in Molecular Psychiatry, researchers have found that the gene encoding phospholipase Cγ1 (PLCγ1) is linked to bipolar disorder or manic-depression. This finding could accelerate research into new treatments for the manic symptoms associated with the condition.

The PLCγ1 has once 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.

In the present study, Professor Suh Pann-Ghill and his team from Ulsan National Institute of Science and Technology (UNIST) created forebrain-specific PLCγ1-deficient mice and observed what happened in the brain synapse of this mouse.

To test whether dysfunction of PLCγ1 in the brain contributes to development of neuropsychiatric disorders, the research team generated mouse models, lacking PLCγ1 in the forebrain and studied the synaptic and neuronal changes in mouse models.

The research team 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. This resulted in the imbalance between excitatory and inhibitory synaptic transmission in forebrain circuits, leading to behavioral abnormalities and manic episodes of bipolar disorder. 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,” said 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 ten years of research, we have finally revealed PLCγ1 protein plays a major role in the onset of bipolar disorder,” said Suh. “Our 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.”

The article can be found at: Yang et al. (2017) Forebrain-specific Ablation of Phospholipase Cγ1 Causes Manic-like Behavior.


Source: Ulsan National Institute of Science and Technology; Photo: Pixabay.
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