Small molecule keeps new adult neurons from straying, may be tied to schizophrenia

A small stretch of ribonucleic acid called microRNA could make the difference between a healthy adult brain and one that’s prone to disorders including schizophrenia.

Scientists at the Salk Institute discovered that miR-19 guides the placement of new neurons in the adult brain, and the molecule is disrupted in cells from patients with schizophrenia.

The findings, published in the journal Neuron on July 6, 2016, pave the way toward a better understanding of how the adult brain controls the growth of new neurons and how it can go wrong.

Salk Professor Rusty Gage, first author Jinju Han and their colleagues found that levels of miR-19 changed more than levels of any other microRNA when precursors to new brain cells in these areas (called neural progenitor cells) were coaxed to become neurons in the adult brain. The researchers went on to show that when miR-19 was blocked in neural progenitor cells, levels of RNA corresponding to a gene called Rapgef2 were altered. Moreover, new neurons did not migrate to the correct areas of the brain.

Because the incorrect migration of new brain cells has been implicated in neuropsychiatric disorders like schizophrenia, Gage’s group next analyzed the levels of miR-19 and Rapgef2 in neural progenitor cells that had been created by reprogramming skin cells from schizophrenic patients. Although the patients had no mutations in the gene for Rapgef2, they had high levels of miR-19 that corresponded with low levels of both the RNA and protein for Rapgef2. The team is now studying the role of miR-19 in mouse models of schizophrenia, as well as looking at cells from broader cohorts of human patients.