Psychotic Mice to the Rescue: Curing Schizophrenia

In the middle of the cage, three white mice play together. They run in circles, reach out for one another, and climb over each other as if playing a rowdy game of tag. In the corner of the cage, another mouse sits alone, avoiding the others. When one of its siblings comes over, perhaps checking up on the mouse to see what's wrong, the lone mouse beings to dart wildly around the cage, doing everything it can to avoid contact with its littermates.

The abnormal behavior of the solitary mouse can be partially explained by its genetic makeup. Studies at the University of Texas Southwestern Medical Center have recently shown that mice with genetic mutations in gene NPAS3, NPAS1, or both, become drastically antisocial. This coincides with earlier evidence showing that a Canadian family with mutations in the human gene NPAS3 suffered from schizophrenia. Both schizophrenia patients and these antisocial mice also have low levels of the protein reelin, which is believed to play a role in the embryonic development of the brain and in signaling in the brain later in life.

"These mice display certain deficits that are potentially consistent with schizophrenia," said Dr. Steven McKnight, head of the study and chairman of biochemistry at UT Southwestern. It is possible that these antisocial mice are suffering from a form of schizophrenia.

The brain disease schizophrenia

Schizophrenia is a chronic and disabling brain disease that affects 2 million Americans annually. This disease affects both men and women equally, but it generally appears in men in their early twenties and women in their late twenties. Many schizophrenics experience high energy levels, as demonstrated by the mouse that ran wildly around the cage. Most schizophrenics hear voices in their heads, believe that people are trying to hurt them, suspect that people are not who they claim to be, or experience other types of hallucinations. As a result, patients become antisocial and fearful of all people, as with the abnormal mouse. Currently, researchers have made few advances in schizophrenia research, none of which have considerably relieved the symptoms of schizophrenia.

Tenuous observations may lead to new treatments

However, these mice may not actually suffer from schizophrenia.

"We recognize that the connection of our study to human psychosis or schizophrenia is very tenuous," said McKnight. "It's difficult to draw direct parallels between the simple behavioral abnormalities observed in the mutant mice and the complex, delusional cognitive defects that characterize human schizophrenia. Our results may turn out to have nothing to do with schizophrenia, or they could point to something more substantial."

McKnight's idea that schizophrenia might be partially caused by a mutation in genes NPAS1 or NPAS3 is a first step to finding needed treatments for this disease. Although very little is known about these genes, it is accepted that they are active in brain cells known as neurons. They affect a particular type of neuron, the inhibitory neuron, which lessens the electrical signals that pass through the common excitatory neurons. If either NPAS1 or NPAS3 suffer a deletion, the inhibitory neurons may function improperly, resulting in more electrical signals being passed through the brain than normal. This faster firing of excitatory neurons due to mutated NPAS1 or NPAS3 probably causes the excess energy that schizophrenic patients experience.

This study significantly progresses the current state of schizophrenia research. With additional evidence that mutations in NPAS1 and NPAS3 cause schizophrenia and the knowledge that the genes are mostly active in the inhibitory neurons, scientists can make drugs that affect these genes, specifically targeting the disease. Current treatments like hallucinogens that are currently prescribed to schizophrenics focus more on treating the symptoms of schizophrenia instead of the disease itself. This research on the psychotic mice will aid scientists in developing drugs to treat schizophrenia and will help combat a disease that is prevalent throughout the world.


References and Suggested Reading

"Mice Experiment May Aid Study of Psychosis." Reuters, 30 August 2004. MSNBC News, 25 September 2004 .

JYI staff members in the Research Department help student authors every step of the writing, editing, and peer-review process.
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