The study reveals that the gene, known as Disrupted-In-Schizophrenia 1 (DISC1), directs the incorporation of new neurons into the adult brain and keeps the process under control. The gene's newly discovered roles might help to explain why schizophrenia's symptoms generally arise in adolescence or early adulthood, the researchers suggested.
The research team found that mice with reduced DISC1 levels in just a few new brain cells showed accelerated integration of those neurons into the existing brain circuitry. The abnormally shaped neurons that resulted from the flurried activity also wound up positioning themselves improperly. What's more, the DISC1-deficient newborn neurons were increasingly excitable and developed a greater number of junctions, or synapses, with other brain cells.
“Everything is happening faster than it's supposed to happen,” said Guo-li Ming of Johns Hopkins University School of Medicine.
“Normally, new neurons migrate within certain ranges, but cells with reduced DISC1 overshoot and end up in the wrong place,” added Hongjun Song, also of Johns Hopkins. “They also grow a lot more dendritic processes and fire at a faster rate. Synapse formation is much faster. A series of things go wrong, and everything is sped up. It appears that they just can't stop somehow.” Dendritic processes are the branches found at neurons' receiving ends.
“This study reveals two unexpected functions of DISC1 [in the adult brain]: regulation of synapse formation and neuronal firing,” said study collaborator Bai Lu of the National Institute of Mental Health, adding that abnormalities of those neural functions have been implicated in the pathogenesis of schizophrenia.
The exact consequences of the new brain cells' fast-paced behavior aren't yet clear, the researchers said. Indeed, the functional role of neurons that are born during adulthood, a process known as adult neurogenesis, remains open to question. However, some studies have suggested that the newborn neurons are important for learning and memory—playing a possible role in song birds' ability to learn new tunes, for example, Ming added. Adult neurogenesis has also been implicated in mood disorders such as depression, Lu said.
Schizophrenia is a chronic, severe, and disabling brain disorder that affects about 1 percent of Americans, according to the National Institute of Mental Health. People with the condition may hear voices or believe others are plotting against them.
Mutations in the gene encoding DISC1 had been linked to schizophrenia and other mood disorders, including depression and bipolar disorder, in multiple family pedigrees, the researchers said. Yet, the neurobiology of the DISC1 protein in the normal developing and adult brain and its roles in these mental illnesses haven't been well understood.