A recent study conducted by researchers from the University of Toronto and Kyushu University has revealed that increased neuron formation and rewiring of neural circuits in the hippocampus, achieved through exercise or genetic manipulation, can help mice forget traumatic or drug-associated memories. Published in Molecular Psychiatry, this breakthrough finding could potentially pave the way for new treatments for mental health conditions such as post-traumatic stress disorder (PTSD) or drug addiction. PTSD is a common mental health condition triggered by experiencing or witnessing a traumatic event, leading to symptoms like vivid flashbacks and avoidance behaviors. While current treatments for PTSD include therapy and medications like anti-depressants, alternative approaches are being explored due to varying responses in patients.
The study, led by Assistant Professor Risako Fujikawa from Kyushu University and Professor Paul Frankland from the University of Toronto, aimed to understand how neurogenesis, the process of forming new neurons in the hippocampus, influences the ability to forget fear memories. The hippocampus, responsible for recording memories linked to specific places and contexts, generates new neurons daily in an area called the dentate gyrus. It was hypothesized that the integration of new neurons into neural circuits disrupts the ability to recall memories, potentially aiding in the forgetting of strong traumatic memories. This was tested by exposing mice to two shocks in different settings, resulting in PTSD-like behaviors and an inability to forget the traumatic memory.
To determine if exercise could alleviate PTSD-like behaviors in mice, the researchers provided some mice with access to a running wheel, known to boost neurogenesis. Mice with increased numbers of newly-formed neurons in their hippocampi showed milder PTSD-like symptoms after four weeks. Additionally, exercising before the second shock prevented some PTSD-like behaviors from developing in mice. However, while the impact of exercise was significant, it was unclear whether it was solely due to hippocampal circuit rewiring by neurogenesis or other factors. Further genetic approaches were utilized to isolate the effect of newborn neuron integration on the hippocampus, resulting in reduced PTSD symptoms but less effect on anxiety levels compared to exercise.
In addition to PTSD, the researchers investigated whether increased neurogenesis and hippocampus re-modeling could aid individuals struggling with substance use disorders. Mice were conditioned to associate a specific room with cocaine use, and methods to boost neurogenesis and hippocampus re-modeling were employed to help them forget this association. The results showed that through exercise and genetic manipulation, the mice no longer exhibited a preference for the room where cocaine was administered, suggesting a reduction in the memory link between the room and the drug. This finding supports the potential for new treatments targeting neurogenesis or hippocampus re-modeling for PTSD and drug dependence.
Looking ahead, Risako plans to explore pharmaceutical interventions that can enhance neurogenesis or hippocampus re-modeling as potential treatments for PTSD and drug addiction. Nevertheless, she emphasizes the crucial role of exercise based on their study results, which demonstrated its significant influence in reducing symptoms of PTSD and drug dependence in mice. Clinical studies in humans have also highlighted the effectiveness of exercise in managing these conditions, underscoring its importance in promoting mental health and overall well-being.