Dietary restriction rescues adaptive behaviors in stress-vulnerable phenotyped rats

wing to stress, animals can respond and survive in a threatening environment by activating various neural and endocrine systems (allostasis). Stress, however, can also cause a range of physical and mental pathologies if it persists (allostatic load).

A salient aspect of stress relates to its impact on metabolism and energy balance. An adaptive stress-response regulates energy mobilization to meet the coping demands imposed by stressors. Consequently, a deregulated stress response impairs energy homeostasis and vice versa.

Dietary restriction (DR), by contrast, improves bioenergetics, and stimulates stress resistance pathways. However, very few neuro-behavioral studies have explored the beneficial effects DR outside models of age-related neuro-pathologies. Therefore, as a proof of concept, in my master’s thesis, we set out to explore DR’s-therapeutic potential for stress-induced psychopathologies, by utilizing the “behavioral profiling method”.

Towards that end, after exposing the animals to stress, “individual Behavioral Profiling” tool was used to identify, prior to the DR-intervention, the stress-affected (vulnerable) population, which were then subjected to 5-weeks of DR.

  The DR-intervention induced a robust recovery rate; by rescuing adaptive behaviors in 61 % of the stress-affected rats. The DR-induced recovery was not associated alterations of functional plasticity, nor in local circuits activity of the Hippocampus. Due to the fact that animals were challenged in the behavioral settings, while in the electrophysiological settings-a challenging stimulus was absent; we interpret these findings as the fallowing: what separates the DR-recovered animals, from the unrecovered, is not how they function at steady-state conditions; but rather, how they adapt when they are challenged.

To the best of our knowledge, we have shown for the first time that DR holds therapeutic potential for stress-related psychopathologies. Based on these preliminary, but promising results, in my current PHD project we intend to continue exploring this fascinating relationship between DR and stress-resilience; by utilizing the behavioral and molecular methods in our lab. Our goal is to identify biomarkers that differentiate between responders and non-responders to the treatment of DR, in order to uncover the underlying mechanisms of DR’s potential efficacy for treating PTSD-like symptoms