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Researchers Reverse Cognitive Symptoms of Schizophrenia in Mice

25 Feb 2016

February 26, 2016. Cognitive problems are a core feature of schizophrenia, including impairments in memory, attention, executive function, and social functioning. Researchers at Columbia University have now succeeded in preventing memory impairments in a mouse model for some aspects of schizophrenia, they wrote in an article published February 18 in the journal Neuron.

They did that by treating very young mice with a compound that interferes with the enzyme GSK3. From previous work, the researchers knew that GSK3 is elevated in the mice, which carry a genetic mutation known to increase the risk of schizophrenia in humans. The inhibitor lowered GSK3 and allowed the mice to undergo normal brain development. As adults, the animals showed similar brain function and performed like normal mice in a maze designed to test their place memory.

The work suggests that GSK3 could represent a target for treating some symptoms of schizophrenia, but there are limitations, according to Joseph Gogos, who led the study along with Joshua Gordon. The mutation they studied in the mice—a deletion of multiple genes on chromosome 22—is rare in humans, and accounts for a very small number of the total cases of schizophrenia.

It is not clear if inhibiting GSK3 would work in more common forms of the disease, which do not feature the same mutation. Also, based on the mouse work so far, treatment might have to start at birth and continue for years, long before schizophrenia symptoms are present. The researchers are continuing studies with the mice to learn more about when and for whom the treatment might work.

In a second study using the same mice, Gogos and Vivien Chevaleyre, of the CNRS in Paris, France, highlight another circuit leading to different types of cognitive changes involving neurons in the hippocampus that caused the mice to have problems remembering social cues. The work shows how the same mutation acts through different neurons and brain circuits to cause different symptoms and raises the possibility of using the mice to discover new therapeutic targets for social symptoms, too. (For more details, see the related news story.)—Pat McCaffrey.