Lipidomic remodeling of the brain and muscle in a zebrafish model of depression.
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| Natura: | Artículo científico |
| Lingua: | en |
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Journal of affective disorders
2026
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| author | Pinto, Bruno Santos, Niedja Domingues, Pedro Ferreira, Helena Beatriz Pinho, Marisa Melo, Tânia Domingues, Inês Domingues, M Rosário |
| author_facet | Pinto, Bruno Santos, Niedja Domingues, Pedro Ferreira, Helena Beatriz Pinho, Marisa Melo, Tânia Domingues, Inês Domingues, M Rosário Pinto, Bruno Santos, Niedja Domingues, Pedro Ferreira, Helena Beatriz Pinho, Marisa Melo, Tânia Domingues, Inês Domingues, M Rosário |
| collection | PubMed - marine biology |
| contents | Lipidomic remodeling of the brain and muscle in a zebrafish model of depression. Pinto, Bruno Santos, Niedja Domingues, Pedro Ferreira, Helena Beatriz Pinho, Marisa Melo, Tânia Domingues, Inês Domingues, M Rosário Animals Zebrafish Disease Models, Animal Lipidomics Brain Major Depressive Disorder Muscle, Skeletal Stress, Psychological Lipid Metabolism Fatty Acids, Omega-3 Behavior, Animal Phospholipids Hydrocortisone Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric condition, increasingly recognized as a systemic disorder involving central and peripheral pathophysiological alterations. In this study, we used a multidimensional approach using zebrafish (Danio rerio) exposed to an unpredictable chronic stress (UCS) protocol as a model of MDD, to unravel the plasticity of the lipidome in this mental disorder. Behavioral analyses revealed a reduction in sociability and locomotor activity in stressed animals, accompanied by significantly elevated cortisol levels. Fatty acid profiling demonstrated a decrease in n-3 (omega-3) polyunsaturated fatty acids (PUFA) and an increase in n-3 (omega-6) PUFA, which was more evident in the brain than in the muscle. After UCS, lipidomic analysis revealed a remodeling of the brain lipid profile, including the modulation of several phospholipid and sphingolipid species that may impact cell membrane properties and cause neuronal dysfunction. Some of these species have been previously correlated with neuroinflammation and impaired neurotransmission. An increase in plasmalogen phospholipids, well-known endogenous oxidant signaling molecules, suggests a dysregulation of the redox state. In muscle, lipidomic alterations were characterized by elevated levels of acylcarnitines, indicative of altered mitochondrial energy metabolism, and ceramides, well-known pro-inflammatory and pro-apoptotic molecules. This study highlights the relevance of lipidomic plasticity in the pathophysiology of MDD, associated with behavioral effects similar to MDD symptoms. |
| format | Artículo científico |
| id | pubmed_41850615 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Journal of affective disorders |
| record_format | pubmed |
| spellingShingle | Lipidomic remodeling of the brain and muscle in a zebrafish model of depression. Pinto, Bruno Santos, Niedja Domingues, Pedro Ferreira, Helena Beatriz Pinho, Marisa Melo, Tânia Domingues, Inês Domingues, M Rosário Animals Zebrafish Disease Models, Animal Lipidomics Brain Major Depressive Disorder Muscle, Skeletal Stress, Psychological Lipid Metabolism Fatty Acids, Omega-3 Behavior, Animal Phospholipids Hydrocortisone Lipidomic remodeling of the brain and muscle in a zebrafish model of depression. Pinto, Bruno Santos, Niedja Domingues, Pedro Ferreira, Helena Beatriz Pinho, Marisa Melo, Tânia Domingues, Inês Domingues, M Rosário Animals Zebrafish Disease Models, Animal Lipidomics Brain Major Depressive Disorder Muscle, Skeletal Stress, Psychological Lipid Metabolism Fatty Acids, Omega-3 Behavior, Animal Phospholipids Hydrocortisone Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric condition, increasingly recognized as a systemic disorder involving central and peripheral pathophysiological alterations. In this study, we used a multidimensional approach using zebrafish (Danio rerio) exposed to an unpredictable chronic stress (UCS) protocol as a model of MDD, to unravel the plasticity of the lipidome in this mental disorder. Behavioral analyses revealed a reduction in sociability and locomotor activity in stressed animals, accompanied by significantly elevated cortisol levels. Fatty acid profiling demonstrated a decrease in n-3 (omega-3) polyunsaturated fatty acids (PUFA) and an increase in n-3 (omega-6) PUFA, which was more evident in the brain than in the muscle. After UCS, lipidomic analysis revealed a remodeling of the brain lipid profile, including the modulation of several phospholipid and sphingolipid species that may impact cell membrane properties and cause neuronal dysfunction. Some of these species have been previously correlated with neuroinflammation and impaired neurotransmission. An increase in plasmalogen phospholipids, well-known endogenous oxidant signaling molecules, suggests a dysregulation of the redox state. In muscle, lipidomic alterations were characterized by elevated levels of acylcarnitines, indicative of altered mitochondrial energy metabolism, and ceramides, well-known pro-inflammatory and pro-apoptotic molecules. This study highlights the relevance of lipidomic plasticity in the pathophysiology of MDD, associated with behavioral effects similar to MDD symptoms. |
| title | Lipidomic remodeling of the brain and muscle in a zebrafish model of depression. |
| topic | Animals Zebrafish Disease Models, Animal Lipidomics Brain Major Depressive Disorder Muscle, Skeletal Stress, Psychological Lipid Metabolism Fatty Acids, Omega-3 Behavior, Animal Phospholipids Hydrocortisone |
| url | https://pubmed.ncbi.nlm.nih.gov/41850615/ |