Departamento de Psicobiologia y Metodología de las CC, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga; Malaga 29071, Spain.
Unidad de Gestion Clínica de Salud Mental, Instituto de Investigacion Biomedica de Malaga (IBIMA), Hospital Regional Universitario de Malaga; Malaga 29010, Spain.
Curr Neuropharmacol. 2018 Mar 5;16(3):271-283. doi: 10.2174/1570159X15666170710200352.
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.
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.
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.
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.
慢性应激会影响健康和生活质量，由于该人群的心理生物学特征，其影响在衰老中尤为相关。然而，尽管有些人会出现精神障碍，特别是抑郁症，但其他人似乎非常有能力应对逆境。毫无疑问，随着与抑郁发生相关的神经生物学机制的确定，发现哪些因素参与在极端困难情况下的积极适应，对于促进适应力至关重要。
在这里，我们回顾了我们实验室的最新工作，使用缺乏 LPA1 受体的动物模型，以及药理学研究和临床证据，表明 LPA1 受体可能参与情绪调节和对慢性应激的应对反应。
大量证据表明，LPA1 受体参与情绪调节和应对慢性应激的反应，如果功能失调，可能会导致对压力的脆弱性和易患抑郁症的倾向。考虑到涉及压力的负面后果和衰老的机制之间存在共同性，这并不奇怪，因为 LPA1 受体可能参与了衰老过程中的逆境应对。
该受体的改变可能是老年人群中存在抑郁症和认知缺陷的易感因素。然而，由于这只是基于先前数据的一个有前途的假设，未来的研究应该集中在 LPA-LPA1 途径在应对压力和衰老中的适应力上。
