Friday, March 28, 2014

Chronic Stress in Early Life Causes Anxiety and Aggression in Adulthood,

"In recent years, behavioral neuroscientists have debated the meaning and significance of a plethora of independently conducted experiments seeking to establish the impact of chronic, early-life stress upon behavior – both at the time that stress is experienced, and upon the same individuals later in life, during adulthood.

These experiments, typically conducted in rodents, have on the one hand clearly indicated a link between certain kinds of early stress and dysfunction in the neuroendocrine system, particularly in the so-called HPA axis (hypothalamic-pituitary-adrenal), which regulates the endocrine glands and stress hormones including corticotropin and glucocorticoid.

Yet the evidence is by no means unequivocal. Stress studies in rodents have also clearly identified a native capacity, stronger in some individuals than others, and seemingly weak or absent in still others, to bounce back from chronic early-life stress. Some rodents subjected to early-life stress have no apparent behavioral consequences in adulthood – they are disposed neither to anxiety nor depression, the classic pathologies understood to be induced by stress in certain individuals.

This week, a research team led by Associate Professor Grigori Enikolopov of Cold Spring Harbor Laboratory (CSHL) reports online in the journal PlOS One the results of experiments designed to assess the impacts of social stress upon adolescent mice, both at the time they are experienced and during adulthood. Involving many different kinds of stress tests and means of measuring their impacts, the research indicates that a “hostile environment in adolescence disturbs psychoemotional state and social behaviors of animals in adult life,” the team says.

The tests began with 1-month-old male mice – the equivalent, in human terms of adolescents – each placed for 2 weeks in a cage shared with an aggressive adult male. The animals were separated by a transparent perforated partition, but the young males were exposed daily to short attacks by the adult males. This kind of chronic activity produces what neurobiologists call social-defeat stress in the young mice. These mice were then studied in a range of behavioral tests.

The image shows a slice of a mouse hippocampus with the interneurons and mossy fibers dyed.
Stressed mice also had less new nerve-cell growth (neurogenesis) in a portion of the hippocampus known to be affected in depression. The image is a stained hippocampal slice from a mouse showing mossy fibers and interneurons. This image is not connected to the research and is for illustrative purposes only. Credit NIH.
“The tests assessed levels of anxiety, depression, and capacity to socialize and communicate with an unfamiliar partner,” explains Enikolopov. They showed that in young mice, chronic social defeat induced high levels of anxiety and helplessness, and less social interaction, including diminished ability to communicate with other young animals. Stressed mice also had less new nerve-cell growth (neurogenesis) in a portion of the hippocampus known to be affected in depression: the subgranular zone of the dentate gyrus.

Another group of young mice was also exposed to social stress, but was then placed for several weeks in an unstressful environment. Following this “rest” period, these mice, now old enough to be considered adults, were tested in the same manner as the other cohort.

In this second, now-adult group, most of the behaviors impacted by social defeat returned to normal, as did neurogenesis, which retuned to a level seen in healthy controls. “This shows that young mice, exposed to adult aggressors, were largely resilient biologically and behaviorally,” says Enikolopov.

However, in these resilient mice, the team measured two latent impacts on behavior. As adults they were abnormally anxious, and were observed to be more aggressive in their social interactions. “The exposure to a hostile environment during their adolescence had profound consequences in terms of emotional state and the ability to interact with peers,” Enikolopov observes.

Notes about this neuroscience and anxiety research
The research described in this release was supported by the Russian Foundation for Basic Research and by the National Institute of Mental Health.

Contact: Peter Tarr – Cold Spring Harbor Laboratory
Source: Cold Spring Harbor Laboratory press release
Image Source: The image is credited to the NIH and is in the public domain
Original Research: Full open access research for “Extended Effect of Chronic Social Defeat Stress in Childhood on Behaviors in Adulthood” by Irina L. Kovalenko, Anna G. Galyamina, Dmitry A. Smagin, Tatyana V. Michurina, Natalia N. Kudryavtseva and Grigori Enikolopov in PLOS ONE. Published online March 25 2014 doi:10.1371/journal.pone.0091762

Open Access Neuroscience Abstract
Extended Effect of Chronic Social Defeat Stress in Childhood on Behaviors in Adulthood

Individuals exposed to social stress in childhood are more predisposed to developing psychoemotional disorders in adulthood. Here we use an animal model to determine the influence of hostile social environment in adolescence on behavior during adult life. One-month-old adolescent male mice were placed for 2 weeks in a common cage with an adult aggressive male. Animals were separated by a transparent perforated partition, but the adolescent male was exposed daily to short attacks from the adult male. After exposure to social stress, some of the adolescent mice were placed for 3 weeks in comfortable conditions. Following this rest period, stressed young males and adult males were studied in a range of behavioral tests to evaluate the levels of anxiety, depressiveness, and communicativeness with an unfamiliar partner. In addition, adult mice exposed to social stress in adolescence were engaged in agonistic interactions. We found that 2 weeks of social stress result in a decrease of communicativeness in the home cage and diminished social interactions on the novel territory. Stressed adolescents demonstrated a high level of anxiety in the elevated plus-maze test and helplessness in the Porsolt test. Furthermore, the number of dividing (BrdU-positive) cells in the subgranular zone of the dentate gyrus was significantly lower in stressed adolescents. After 3 weeks of rest, most behavioral characteristics in different tests, as well as the number of BrdU-positive cells in the hippocampus, did not differ from those of the respective control mice. However, the level of anxiety remained high in adult males exposed to chronic social stress in childhood. Furthermore, these males were more aggressive in the agonistic interactions. Thus, hostile social environment in adolescence disturbs psychoemotional state and social behaviors of animals in adult life.

“Extended Effect of Chronic Social Defeat Stress in Childhood on Behaviors in Adulthood” by Irina L. Kovalenko, Anna G. Galyamina, Dmitry A. Smagin, Tatyana V. Michurina, Natalia N. Kudryavtseva and Grigori Enikolopov in PLOS ONE. March 25 2014 doi:10.1371/journal.pone.0091762

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