The Comorbidity of Depression and Diabetes Is Involved in the Decidual Protein Induced by Progesterone 1 (Depp1) Dysfunction in the Medial Prefrontal Cortex
Background: There is a high rate of depressive symptoms such as irritability, anhedonia, fatigue, and hypersomnia in patients with type 2 diabetes mellitus (T2DM). However, the causes and underlying mechanisms of the comorbidity of depression and diabetes remain unknown. Methods: For the first time,...
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2025-01-01
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| author | Chen Xu Mengxing Liao Shize Zhang Yuang Chen Xinyue Shulai Guangji Wang Jiye Aa |
| author_facet | Chen Xu Mengxing Liao Shize Zhang Yuang Chen Xinyue Shulai Guangji Wang Jiye Aa |
| author_sort | Chen Xu |
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| description | Background: There is a high rate of depressive symptoms such as irritability, anhedonia, fatigue, and hypersomnia in patients with type 2 diabetes mellitus (T2DM). However, the causes and underlying mechanisms of the comorbidity of depression and diabetes remain unknown. Methods: For the first time, we identified Decidual protein induced by progesterone 1 (Depp1), also known as DEPP autophagy regulator 1, as a hub gene in both depression and T2DM models. Depp1 levels were increased in the mPFC but not in other brain regions, such as the hippocampus or nucleus accumbens, according to Western blot and PCR assays. Results: Glucose dysregulation and synaptic loss occur in both depression and T2DM. The typical hyperglycemia in T2DM was observed in two models of depression, namely, chronic social defeat stress (CSDS) and chronic restraint stress (CRS). Hyperglycemia, which occurred in T2DM, was observed, and metabolomics data clearly showed the perturbation of glucose levels and glucose metabolism in the medial prefrontal cortex (mPFC). Decreased protein levels of BDNF and PSD95 suggested significant synaptic loss in depressed and diabetic mice. Conclusion: These findings suggest that the comorbidity of depression and diabetes is involved in the dysfunction of Depp1 in the mPFC. |
| format | Article |
| id | doaj-art-839e251310684c96830c47fdfdfc9ac5 |
| institution | Kabale University |
| issn | 2218-1989 |
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| publishDate | 2025-01-01 |
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| spelling | doaj-art-839e251310684c96830c47fdfdfc9ac52025-01-24T13:41:14ZengMDPI AGMetabolites2218-19892025-01-011513410.3390/metabo15010034The Comorbidity of Depression and Diabetes Is Involved in the Decidual Protein Induced by Progesterone 1 (Depp1) Dysfunction in the Medial Prefrontal CortexChen Xu0Mengxing Liao1Shize Zhang2Yuang Chen3Xinyue Shulai4Guangji Wang5Jiye Aa6Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, ChinaJiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, ChinaJiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, ChinaJiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, ChinaJiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, ChinaJiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, ChinaJiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, ChinaBackground: There is a high rate of depressive symptoms such as irritability, anhedonia, fatigue, and hypersomnia in patients with type 2 diabetes mellitus (T2DM). However, the causes and underlying mechanisms of the comorbidity of depression and diabetes remain unknown. Methods: For the first time, we identified Decidual protein induced by progesterone 1 (Depp1), also known as DEPP autophagy regulator 1, as a hub gene in both depression and T2DM models. Depp1 levels were increased in the mPFC but not in other brain regions, such as the hippocampus or nucleus accumbens, according to Western blot and PCR assays. Results: Glucose dysregulation and synaptic loss occur in both depression and T2DM. The typical hyperglycemia in T2DM was observed in two models of depression, namely, chronic social defeat stress (CSDS) and chronic restraint stress (CRS). Hyperglycemia, which occurred in T2DM, was observed, and metabolomics data clearly showed the perturbation of glucose levels and glucose metabolism in the medial prefrontal cortex (mPFC). Decreased protein levels of BDNF and PSD95 suggested significant synaptic loss in depressed and diabetic mice. Conclusion: These findings suggest that the comorbidity of depression and diabetes is involved in the dysfunction of Depp1 in the mPFC.https://www.mdpi.com/2218-1989/15/1/34depressiondiabetesglucose metabolismDEPP1mPFCsynaptic protein |
| spellingShingle | Chen Xu Mengxing Liao Shize Zhang Yuang Chen Xinyue Shulai Guangji Wang Jiye Aa The Comorbidity of Depression and Diabetes Is Involved in the Decidual Protein Induced by Progesterone 1 (Depp1) Dysfunction in the Medial Prefrontal Cortex Metabolites depression diabetes glucose metabolism DEPP1 mPFC synaptic protein |
| title | The Comorbidity of Depression and Diabetes Is Involved in the Decidual Protein Induced by Progesterone 1 (Depp1) Dysfunction in the Medial Prefrontal Cortex |
| title_full | The Comorbidity of Depression and Diabetes Is Involved in the Decidual Protein Induced by Progesterone 1 (Depp1) Dysfunction in the Medial Prefrontal Cortex |
| title_fullStr | The Comorbidity of Depression and Diabetes Is Involved in the Decidual Protein Induced by Progesterone 1 (Depp1) Dysfunction in the Medial Prefrontal Cortex |
| title_full_unstemmed | The Comorbidity of Depression and Diabetes Is Involved in the Decidual Protein Induced by Progesterone 1 (Depp1) Dysfunction in the Medial Prefrontal Cortex |
| title_short | The Comorbidity of Depression and Diabetes Is Involved in the Decidual Protein Induced by Progesterone 1 (Depp1) Dysfunction in the Medial Prefrontal Cortex |
| title_sort | comorbidity of depression and diabetes is involved in the decidual protein induced by progesterone 1 depp1 dysfunction in the medial prefrontal cortex |
| topic | depression diabetes glucose metabolism DEPP1 mPFC synaptic protein |
| url | https://www.mdpi.com/2218-1989/15/1/34 |
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