Editors' ChoiceSTRESS

Stressed out? Making new, but different, neurons

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Science Translational Medicine  14 Feb 2018:
Vol. 10, Issue 428, eaar7533
DOI: 10.1126/scitranslmed.aar7533

Abstract

Neurons born when coping with stress respond differently to subsequent stress.

Chronic stress is a pervasive problem in our society, and how we (and our brains) cope with and adapt to stress remains an important question. It is well established that neurogenesis occurring during adulthood is profoundly affected by stress: decreased during the acute phase of stress and increased upon recovery. But are neurons born when coping with stress similar to neurons born in normal conditions? Do they help to cope with stress, or perhaps are they responsible for some of the more negative aspects of chronic stress such as mental health issues? In this study, De Miguel et al. begin to address these questions.

They focused on the dentate gyrus of the hippocampus, one of the regions of active neurogenesis during adulthood that is known to be important for spatial learning. They used a chronic social stress paradigm in mice, in which male mice were routinely exposed to highly aggressive counterparts over a 2-week period, and labeled neurons born during the last 5 days, a time when mice had learnt coping mechanisms (and were no longer being attacked). They found a significant increase in the number of newborn neurons compared with unstressed controls, suggesting that this coping period is similar to recovery from stress. When spatial learning was tested in a water maze 10 weeks later, these newborn neurons were activated by learning, confirming previous studies showing that they can integrate into functional hippocampal circuits. However, after the mice were exposed to a second 2-week period of stress, these neurons were no longer activated by learning, indicating that they responded differently to stress. In addition, the second stress episode appeared to induce a loss of dendritic spines and branches in these neurons, which was not seen in neurons born in unstressed animals, suggestive of a reduction in connectivity. These results demonstrate that neurons born during the “coping period” respond in a unique way to subsequent stress. Whether the differences described here have long-term behavioral consequences remains to be seen; however, understanding brain responses to chronic stress might help to elucidate the mechanisms underlying the correlation between stress and the risk of associated psychiatric disorders, such as anxiety and depression.

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