WASHINGTON, May 17 (Xinhua) -- American researchers have discovered that social isolation could cause the build-up of a particular chemical in the brain, thus changing the brain in a profound way.
A study published on Thursday in the journal Cell revealed prolonged social isolation leads to a broad array of behavioral changes in mice, including increased aggressiveness towards unfamiliar mice, persistent fear, and hypersensitivity to threatening stimuli.
It showed that when encountering a threatening stimulus, mice that have been socially isolated remain frozen in place long after the threat has passed, whereas normal mice stop freezing soon after the threat is removed.
These effects are seen when mice are subjected to two weeks of social isolation, but not to short-term social isolation like 24 hours, suggesting that the observed changes in aggression and fear responses require chronic isolation.
The researchers found that social isolation for two weeks in mice resulted in the upregulation of the signaling molecule neuropeptide, tachykinin 2 (Tac2)/neurokinin B (NkB).
According to the researchers, Tac2/NkB is the brain chemical responsible for causing the animals to display much more persistent responses to threatening stimuli compared to group-housed mice.
The researchers found that chronic isolation leads to an increase in Tac2 gene expression and the production of NkB throughout the brain. However, administration of a drug that chemically blocks NkB-specific receptors enabled the stressed mice to behave normally, eliminating the negative effects of social isolation.
Conversely, artificially increasing Tac2 levels and activating the corresponding neurons in normal, unstressed animals led them to behave like the stressed, isolated animals.
The researchers also inhibited the function of Tac2 and its receptors in multiple specific brain regions.
They found that suppressing the Tac2 gene in the amygdala eliminated the increased fear behaviors, but not aggression, while conversely suppressing the gene in the hypothalamus eliminated increased aggression but not persistent fear.
The results imply that Tac2 must increase in different brain regions to produce the various effects of social isolation.
Also, blocking this chemical with osanetant, a drug that blocks NkB receptor, could eliminate the negative effects of isolation, according to the study.
Though the work was done in mice, it has potential implications for understanding how chronic stress affects humans, according to the researchers.
"Humans have an analogous Tac2 signaling system, implying possible clinical translations of this work," said Moriel Zelikowsky, the paper's lead author and a postdoctoral scholar at California Institute of Technology.
Osanetant was previously developed by a potential therapy for schizophrenia and bipolar disorder. While it was safe and well-tolerated in human studies, it failed to show any efficacy for these disorders.
"Our study raises the possibility that this drug might be repurposed to treat other psychiatric disorders that are related to effects of social isolation in humans, not just in solitary confinement but perhaps in bereavement stress or other types of stress," said David J. Anderson, the paper's senior author from the California Institute of Technology.