Exploring Molecular Mechanisms Involved in the Development of the Depression-Like Phenotype in Interleukin-18-Deficient Mice
| Autor: | Seishi Maeda, Wen Li, Kyosuke Yamanishi, Keiichiro Mukai, Hisato Matsunaga, Yuko Watanabe, Hitomi Seino, Sachi Kuwahara-Otani, Haruki Okamura, Masahiro Miyauchi, Hiromichi Yamanishi, Masaki Hata, Takuya Hashimoto, Naomi Gamachi, Noriko Uwa, Hideshi Yagi |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male medicine.medical_specialty Article Subject medicine.medical_treatment Prefrontal Cortex Biology Hippocampal formation General Biochemistry Genetics and Molecular Biology Energy homeostasis Mice Internal medicine Gene expression medicine Animals Humans Prefrontal cortex Mice Knockout Neurons Depressive Disorder General Immunology and Microbiology Depression Interleukin-18 Brain General Medicine Human brain Mice Inbred C57BL Disease Models Animal Transthyretin Cytokine Endocrinology medicine.anatomical_structure biology.protein Medicine Interleukin 18 Research Article |
| Zdroj: | BioMed Research International, Vol 2021 (2021) BioMed Research International |
| ISSN: | 2314-6141 2314-6133 |
| Popis: | Interleukin-18 (IL-18) is an inflammatory cytokine that has been linked to energy homeostasis and psychiatric symptoms such as depression and cognitive impairment. We previously revealed that deficiency in IL-18 led to hippocampal abnormalities and resulted in depression-like symptoms. However, the impact of IL-18 deficiency on other brain regions remains to be clarified. In this study, we first sought to confirm that IL-18 expression in neural cells can be found in human brain tissue. Subsequently, we examined the expression of genes in the prefrontal cortex of Il18−/− mice and compared it with gene expression in mice subjected to a chronic mild stress model of depression. Extracted genes were further analyzed using Ingenuity® Pathway Analysis, in which 18 genes common to both the chronic mild stressed model and Il18−/− mice were identified. Of those, 16 were significantly differentially expressed between Il18+/+ and Il18−/− mice. We additionally measured protein expression of α-2-HS-glycoprotein (AHSG) and transthyretin (TTR) in serum and the brain. In the prefrontal cortex of Il18−/− mice, TTR but not AHSG was significantly decreased. Conversely, in the serum of Il18−/− mice, AHSG was significantly increased but not TTR. Therefore, our results suggest that in IL-18-deficit conditions, TTR in the brain is one of the mediators causally related to depression, and AHSG in peripheral organs is one of the regulators inducing energy imbalance. Moreover, this study suggests a possible “signpost” to clarify the molecular mechanisms commonly underlying the immune system, energy metabolism, neural function, and depressive disorders. |
| Databáze: | OpenAIRE |
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