Chronic stress is a major risk factor for brain disorders, such as depression, and affects the functioning of the hippocampus, a brain region relevant for learning and memory and emotional response. Since the brain is mainly composed of lipids, and since these molecules are relevant for various key cellular processes, these are likely altered in conditions that lead to brain regional dysfunction. Importantly, recent mass-spectrometry approaches allow the identification of functional and dysfunctional lipidomic signatures, and we have used these strategies to study the effects of chronic stress in the brain. Moreover, we studied the hippocampus at the subregional level along its longitudinal axis, since it was previously shown that the dorsal and ventral poles, in rodents, contribute differentially to stress and emotional responses. These lipidomic signatures allow the identification of candidate lipid signalling pathways and we are currently testing the impact of modulating these pathways with genetic rodent models at biochemical, functional and behavioural levels. Overall, the goal of these projects is to identify lipid pathways relevant for brain function and dysfunction with potential implications for the treatment and diagnosis of brain disorders, such as depression.