NARSAD Independent Investigator Dr. Amelia J. Eisch at the University of Texas Southwestern Medical Center at Dallas seeks to explain why some individuals exposed to extreme stress are more susceptible to developing major depressive disorder (MDD) and post-traumatic stress disorder (PTSD), and more resilient individuals exposed to similar levels of stress are not.

She and her team have discovered that weeks after experiencing a stressful event, mice that were more susceptible to stress exhibited enhanced neurogenesis – the birth of new neurons in the brain. Specifically, the neurons that these animals produced after a stressful event survived longer than new brain cells produced by mice that were more resilient to the stress.

While much research has explored how stress influences neurogenesis, little work has been done on the long-lasting effects of stress on neurogenesis after the stress is over. Also, no research has explored whether stress leads to long-lasting adaptations in adult hippocampal neurogenesis that directly affects behavior.

The hippocampus, a brain region critical for memory, is exquisitely responsive to stressful experiences, making it an excellent target for explorations into the neurobiology of resilience. Interestingly, new brain cells are generated in the hippocampus throughout life. Scientists have discovered that this “adult hippocampal neurogenesis” is decreased by stressful experiences, stimulated by antidepressant therapeutics like running, and may contribute to hippocampal functions. Such connections have led researchers to further explore the contribution of adult neurogenesis to mood regulation and even the response to antidepressant treatment.

In this study, when Dr. Eisch and her team prevented neurogenesis in both stress-susceptible and resilient mice, the animals previously susceptible to stress became more resilient, highlighting the direct correlation between neurogenesis and behavior traits. In mice exposed to a prolonged stressful psychosocial experience called social defeat, without the prevention of neurogenesis, susceptible mice displayed behavioral and physiological indices reminiscent of MDD and PTSD and avoided an aggressor mouse in a social environment, while resilient mice did not.

“This work shows that there is a period of time during which it may be possible to alter memories relevant to a social situation by manipulating adult-generated neurons in the brain,” Dr. Eisch said. “Understanding the neurobiological underpinnings of this variable response to stress has enormous potential to enhance our comprehension, treatment and even prevention of stress-related disorders like MDD and PTSD.”