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Profiling GABA(A) Receptor Subunit Expression in the Hippocampus of PMDD Rat Models Based on TCM Theories

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Abstract

γ-Aminobutyric acid type A receptors (GABAARs) play an important role in cognitive and emotional regulation and are related to the hippocampus. However, little is known regarding patterns of hippocampal GABAAR subunit expression in rat models of premenstrual dysphoric disorder (PMDD). This study investigated the above changes by establishing two PMDD rat models based on Traditional Chinese Medicine (TCM) theories, namely, PMDD liver-qi invasion syndrome (PMDD-LIS) and PMDD liver-qi depression syndrome (PMDD-LDS). Behavioral tests were used to detect depression and irritability emotion. Western blot analysis was used to investigate protein levels of GABAAR α1, α2, α4, α5, β2, β3, and δ subunits, whereas ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis was performed to determine gamma-aminobutyric acid (GABA) and glutamate (Glu) levels in the hippocampus across each group. Concurrently, behavioral data indicated that the PMDD-LDS and PMDD-LIS rat models had been successfully established. GABAAR α2, α5, β2, and δ subunit was significantly upregulated, whereas α4 was significantly downregulated (P < 0.05) in PMDD-LDS rat models relative to controls. On the other hand, GABAAR α1, α2, and β3 were significantly downregulated while α4 and β2 were significantly upregulated in PMDD-LIS rat models relative to the control group (P < 0.05). Moreover, GABA levels significantly decreased, while Glu and the ratio of glutamate to GABA increased in PMDD-LIS rat models (P < 0.05). Conversely, GABA and Glu levels significantly decreased, whereas the ratio of glutamate to GABA increased in PMDD-LIS rat models (P < 0.05). Conclusively, our results revealed differential expression of GABAAR α1, α2, α4, α5, β2, β3, and δ subunits between PMDD-LIS and PMDD-LDS rat models, suggesting that they may be biomarkers in the pathogenesis of PMDD.

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Data Availability

Data used to support the current study are available from the corresponding author on reasonable request.

Abbreviations

PMDD:

Premenstrual dysphoric disorder

PMS:

Premenstrual syndrome

PMDD-LIS:

Liver-qi invasion syndrome of Premenstrual dysphoric disorder

PMDD-LDS:

Liver-qi depression syndrome of Premenstrual dysphoric disorder

Glu:

Glutamate

TCM:

Traditional Chinese medicine

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Funding

This study was sponsored by Natural Science Foundation of China (No.82204958), Medical and health science and technology development plan project of Shandong Province (202105010467), Traditional Chinese medicine science and technology project of Shandong Province (Q-2022059), Special Funding for Taishan Scholars Project (No. tsqn202211137), the Chinese Medicine and Brain Science Youth Scientific Research Innovation Team, Shandong University of Traditional Chinese Medicine (No. 22202101).

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Authors and Affiliations

  1. Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China

    Hao Zhang

  2. College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China

    Zhan Gao, Dongmei Gao & Mingqi Qiao

  3. Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China

    Ya Sun & Mingzhou Gao

  4. International Exchange and Cooperation Office, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China

    Tian Lu

  5. Qilu Hospital of Shandong University, Jinan, Shandong Province, China

    Zhenzhen Wang

  6. Office of Academic Research, Shandong University of Traditional Chinese Medicine, Jinan , Shandong Province, China

    Jieqiong wang

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  1. Hao Zhang
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  4. Tian Lu
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Contributions

Mingzhou Gao designed experiments. Mingzhou Gao carried out animal experimental modeling and detection of biological indexes with Hao Zhang, Zhan Gao, Tian Lu, Zhenzhen Wang, Gongmei Gao, Jieqiong Wang, and Mingqi Qiao provide assistance. Mingzhou Gao performed statistics and finished the manuscript with Hao Zhang. All the authors read and approved the manuscript.

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Correspondence to Mingzhou Gao.

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Ethics Approval and Consent to Participate

This study was approved by the Institutional Committee for Animal Care and Use of Shandong University of Traditional Chinese Medicine (Approval ID: SDUTCM20190904013) and was performed in accordance with the Guidelines for the Care and Use of Laboratory Animals, formulated by the National Institute of Health, USA.

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Hao Zhang, Zhan Gao, and Ya Sun contributed equally to this work and should be considered co-first authors.

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Zhang, H., Gao, Z., Sun, Y. et al. Profiling GABA(A) Receptor Subunit Expression in the Hippocampus of PMDD Rat Models Based on TCM Theories. Mol Neurobiol 60, 4418–4428 (2023). https://doi.org/10.1007/s12035-023-03354-3

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