Chronic social isolation has serious effects on mental health in mammals: it is often associated with depression and post-traumatic stress disorder in humans, for example. Now, a new study published in the journal Cell and carried out by a team of researchers from Caltech (USA) has discovered that social isolation also causes the accumulation of a specific chemical in the brain , and that Blocking this chemical eliminates the negative effects of isolation, which could have potential applications for treating mental health disorders in humans.
The study, carried out with rodents, confirms and extends previous observations, as the experiments showed that prolonged social isolation leads to a wide range of behavioral changes. These include increased aggressiveness towards unfamiliar mice, persistent fear, and hypersensitivity to threatening stimuli.
For example, when mice encountered a threatening stimulus, those that had been socially isolated remained immobile, petrified in fear, long after the threat had passed, while control mice returned to a normal state shortly after. the threat was removed. These effects were seen with a two-week social isolation, but not with a 24-hour isolation, suggesting that the observed changes in fear and aggression responses require chronic isolation or long-term isolation.
In a previous study of a fly of the genus Drosophila (fruit fly), experts had discovered that a particular neurochemical called tachykinin (with an opiate-like structure) plays a crucial 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, therefore, influencing the function of the neuronal circuit.
To investigate whether the role of tachykinin in controlling social isolation-induced aggression could be evolutionarily conserved from insects to mammals, the scientists 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, that are involved in emotional and social behavior.
The researchers found that chronic isolation led to increased Tac2 gene expression and NkB production throughout the brain.
However, the administration of a drug that chemically blocks specific NkB receptors allowed the stressed mice to behave normally, eliminating the negative effects of social isolation. In contrast, the artificial increase in Tac2 levels and the activation of the corresponding neurons in normal, unstressed animals led them to behave like distressed and isolated animals.
The researchers also inhibited the function of Tac2 and its receptors in multiple specific brain regions. They found that deletion of the Tac2 gene in the amygdala eliminated increased fear behaviors but not aggression , whereas, conversely, deletion of the gene in the hypothalamus eliminated increased aggression but not persistent fear. .
“This approach allowed us to compare the effects of different Tac2 signaling manipulations in the same brain region, as well as to compare the effects of the same manipulation in different brain regions,” explains David J. Anderson, co-author of the work.
Although the experiment was carried out in mice, it has potential implications for understanding how chronic stress affects humans.
“ Humans have an analogous Tac2 signaling system , which implies possible clinical translations of this work,” says Moriel Zelikowsky, leader of the study.
Reference: “The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress” Cell (2018). DOI: 10.1016 / j.cell.2018.03.037
Image credit: Maayan Harel
