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Chronic social isolation has debilitating effects on mental health in mammals, it is associated with depression and post-traumatic stress disorder in humans. A team of Caltech researchers has discovered that social isolation causes the build-up of a particular chemical in the brain, blockIing this chemical eliminates the negative effects of isolation.
The work has potential applications for treating mental health disorders in humans. The research, led by postdoctoral scholar Moriel Zelikowsky, was done in the laboratory of David J. Anderson, Seymour Benzer Professor of Biology, Tianqiao and Chrissy Chen Leadership Chair, Howard Hughes Medical Institute Investigator, and director of the Tianqiao and Chrissy Chen Institute for Neuroscience.
Confirming and extending previous observations, the researchers showed that prolonged social isolation leads to a broad array of behavioral changes in mice. These include increased aggressiveness towards unfamiliar mice, persistent fear, and hypersensitivity to threatening stimuli. For example, when encountering a threatening stimulus, mice that have been socially isolated remain frozen in place long after the threat has passed, while 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, suggesting that the observed changes in aggression and fear responses require chronic isolation. In a previous study of the Drosophila fly, the Anderson laboratory had discovered that a particular neurochemical called tachykinin plays a role in promoting aggression in socially isolated flies.
Tachykinin is a neuropeptide, a short protein molecule that is released from certain neurons when they are activated. Neuropeptides bind to specific receptors on other neurons, altering their physiological properties and thereby influencing neural circuit function.To investigate whether the role of tachykinin in controlling social isolation-induced aggression might be evolutionarily conserved from insects to mammals, researchers turned to laboratory mice.
In mice, the tachykinin gene Tac2 encodes a neuropeptide called neurokinin B (NkB). Tac2/NkB is produced by neurons in specific regions of the mouse brain such as the amygdala and hypothalamus, which are involved in emotional and social behavior. 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.
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