1. Endogenous n-3 PUFAs attenuated olfactory bulbectomy-induced behavioral and metabolomic abnormalities in Fat-1 mice
- Author
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Li Tian, Ling Yan, Peng Li, Eero Vasar, Zhiyou Yang, Min-Qing Gu, Cai Song, and Juan Xia
- Subjects
Fatty Acid Desaturases ,0301 basic medicine ,medicine.medical_specialty ,Immunology ,Mice, Transgenic ,Inflammation ,Endogeny ,Nitric oxide ,Group VI Phospholipases A2 ,Mice ,03 medical and health sciences ,Behavioral Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Phospholipase A2 ,Internal medicine ,Fatty Acids, Omega-3 ,medicine ,Animals ,Humans ,chemistry.chemical_classification ,biology ,Microglia ,Endocrine and Autonomic Systems ,Chemistry ,Lipid metabolism ,Mice, Inbred C57BL ,030104 developmental biology ,Fatty acid desaturase ,Endocrinology ,medicine.anatomical_structure ,Fatty Acids, Unsaturated ,biology.protein ,Cytokines ,lipids (amino acids, peptides, and proteins) ,medicine.symptom ,030217 neurology & neurosurgery ,Polyunsaturated fatty acid - Abstract
Depression is associated with abnormal lipid metabolism, and omega (n)-3 polyunsaturated fatty acids (PUFAs) can effectively treat depression. However, mechanism of lipid metabolism involved in the depressive attenuation remains poorly understood. Olfactory bulbectomy (OB)-induced changes in animal behavior and physiological functions are similar to those observed in depressed patients. Therefore, the present study used wild type (WT) and Fat-1 mice with or without OB to explore whether endogenous n-3 PUFA treatment of depression was through rectifying lipid metabolism, and to discover the possible lipid metabolic pathways. In WT mice, OB enhanced locomotor activity associated with up-regulation of lipid metabolites in the serum, such as phosphatidylcholines, L-a-glutamyl-L-Lysine and coproporphyrinogen III (Cop), which were involved in anti-inflammatory lipid metabolic pathways. OB also increased microglia activation marker CD11b and pro-inflammatory cytokines in the hippocampus. In one of the lipid pathways, increased Cop was significantly correlated with the hyper-activity of the OB mice. These OB-induced changes were markedly attenuated by endogenous n-3 PUFAs in Fat-1 mice. Additionally, increased expressions of anti-inflammatory lipid genes, such as fatty acid desaturase (Fads) and phospholipase A2 group VI (Pla2g6), were found in the hippocampus of Fat-1 mice compared with WT mice. Furthermore, Cop administration increased the production of pro-inflammatory cytokines and nitric oxide in a microglial cell line BV2. In conclusion, endogenous n-3 PUFAs in Fat-1 mice attenuated abnormal behavior in the depression model through restoration of lipid metabolism and suppression of inflammatory response.
- Published
- 2021