Stress, Depression, Resilience and Ageing: A Role for the LPA-LPA1 Pathway

Background: Chronic stress affects health and the quality of life, with its effects being particularly relevant in ageing due to the psychobiological characteristics of this population. However, while some people develop psychiatric disorders, especially depression, others seem very capable of dealing with adversity. There is no doubt that along with the identification of neurobiological mechanisms involved in developing depression, discovering which factors are involved in positive adaptation under circumstances of extreme difficulty will be crucial for promoting resilience. Methods: Here, we review recent work in our laboratory, using an animal model lacking the LPA1 receptor, together with pharmacological studies and clinical evidence for the possible participation of the LPA1 receptor in mood and resilience to stress. Results: Substantial evidence has shown that the LPA1 receptor is involved in emotional regulation and in coping responses to chronic stress, which, if dysfunctional, may induce vulnerability to stress and predisposition to the development of depression. Given that there is commonality of mechanisms between those involved in negative consequences of stress and in ageing, this is not surprising, considering that the LPA1 receptor may be involved in coping with adversity during ageing. Conclusion: Alterations in this receptor may be a susceptibility factor for the presence of depression and cognitive deficits in the elderly population. However, because this is only a promising hypothesis based on previous data, future studies should focus on the involvement of the LPA-LPA1 pathway in coping with stress and resilience in ageing.