Tick, Tick, Tock: The Mouse without the Clock

In a study that could have potentially far-reaching effects for the Bipolar research and treatment, Dr Colleen and her group have reported on a mouse model of bipolar disorder.

The association between circadian rhythms and bipolarity is well established and a bipolar episode is characterized with disruptions in daily sleeping, eating rhythms etc. Till now the biological basis of this was not clear.

In this study, mice with Clock gene knocked out were tested on a number of measures of bipolairty and it was found that these mice lacking the Clock gene, which is essential for proper circadian rhythms, suffered from human manic like symptoms. Moreover treating these bipolar mice with lithium resulted in the subsiding of symptoms.

The study included putting the mutant mice through a series of tests, during which they displayed hyperactivity, decreased sleep, decreased anxiety levels, a greater willingness to engage in “risky” activities, lower levels of depression-like behavior and increased sensitivity to the rewarding effects of substances such as cocaine and sugar.

“These behaviors correlate with the sense of euphoria and mania that bipolar patients experience,” said Dr. McClung. “In addition, there is a very high co-morbidity between drug usage and bipolar disorder, especially when patients are in the manic state.”

During the study, lithium was given to the mutant mice. Lithium, a mood-stabilizing medication, is most commonly used in humans to treat bipolar patients. Once treated with the drug on a regular basis, the majority of the study’s mice reverted back to normal behavioral patterns, as do humans.

The clock gene is expressed widely in the human brain, but the focus till now was only on the area called suprachiasmatic nucleus. In this study the area of brain associated with reward learning, VTA/ Striatum etc was studied and expressing the clock gene there in KO mice resulted in subsiding of symptoms.

The researchers also injected a functional Clock gene protein – basically giving the mice their Clock gene back – into a specific region of the brain that controls reward functions and where dopamine cells are located. Dopamine is a neurotransmitter associated with the “pleasure system” of the brain and is released by naturally rewarding experiences such as food, sex and the use of certain drugs. This also resulted in the mice going back to normal behaviors.

This is an exciting news as it makes a mice model for Bipolairty readily available and would help in clinical testing of new anti psychotics and mood stabilizers.

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