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Genetically Altered Mice Bear Some Hallmarks of Human Bipolar Behavior – Johns Hopkins Medicine

Wednesday, 20 September, 2017

Genetically Altered Mice Bear Some Hallmarks of Human Bipolar Behavior – Johns Hopkins Medicine

Johns Hopkins researchers report they have genetically engineered mice that display many of the behavioral hallmarks of human bipolar disorder, and that the abnormal behaviors the rodents show can be reversed using well-established drug treatments for bipolar disorder, such as lithium.

Specifically, the mice lacked the protein ankyrin-G, in particular neurons in the brain, a defect that appears to make the animals both hyperactive and less fearful, a behavioral profile suggestive of a mania-like state for a mouse. At the same time, the rodents had an even greater response to social defeat stress than normal mice do, suggesting their brains also are more susceptible to a depressive-like state. Human bipolar disease is characterized by swings in “manic” and “depressive” moods.

In a report on the mouse studies, published online Sept. 11 in PNAS (Proceedings of the National Academy of Sciences of the United States of America), the investigators say the genetic alteration appears to release the biochemical “brakes” on brain cells involved in body movement, reasoning and perception of the world, triggering over-excited activity and reactions.

The results of their work, the researchers say, may advance scientific understanding of how genes linked to the risk of human bipolar disorder change neuronal circuits in the brain, and may offer an animal model for testing new treatments. Bipolar disorder is estimated to affect about 5.7 million people, or 2.6 percent of adults in the United States, according the National Institute of Mental Health.

“Mouse behavior isn’t the same as human behavior, so we need to be cautious, but we were surprised and heartened by the fact that the mutant mice responded to lithium treatment — a gold standard for treating human bipolar disorder and alleviating features of mania and depression,” says Christopher Ross, M.D., Ph.D., professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “To our knowledge, this is the first robust mouse model of bipolar disorder based on a genome-wide significant risk factor for the human disorder.” Ross points out that mouse disease models are still unusual in psychiatry, even though with careful interpretation they have proved to be important for understanding and treating many diseases.

Read more at: http://www.hopkinsmedicine.org/news/media/releases/genetically_altered_mice_bear_some_hallmarks_of_human_bipolar_behavior

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