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

Zhang, Hao; Gao, Zhan; Sun, Ya; Liu, Tian; Wang, Zhenzhen; Gao, Dongmei; Wang, Jieqiong; Qiao, Mingqi; Gao, Mingzhou

doi:10.1007/s12035-023-03354-3

Cited by 3 publications

(2 citation statements)

References 52 publications

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“…Fluctuations in steroid hormone levels can influence the structure and function of the GABAA receptor (GABAAR), impacting the expression levels of GABAARg-2 and delta subunits, which are closely associated with the pathophysiology of PMS (94,95). In a study by Zhang et al, analysis of GABA receptor subunit expression patterns in a rat model simulating clinical PMDD symptoms revealed notable differences in the expression of GABAAR a1, a2, a4, a5, b2, b3, and d subunits among PMDD rat models with distinct characteristics, suggesting their potential as biomarkers for PMDD pathogenesis (96). Furthermore, experimental findings by Iba et al indicated that the Japanese herb Inochinohaha White increased the b2-subunit of the GABAA receptor in the amygdala, attenuating anxiety-like behavior in a rat model of progesterone withdrawal through augmentation of the GABAA receptormediated signaling pathway (97).…”

Section: Orexin Inhibited Inflammatory Response To Protect Neuronsmentioning

confidence: 99%

The potential role of the orexin system in premenstrual syndrome

Dong,

Dai,

et al. 2024

Front. Endocrinol.

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Premenstrual syndrome (PMS) occurs recurrently during the luteal phase of a woman’s menstrual cycle and disappears after menstruation ends. It is characterized by abnormal changes in both the body and mood, and in certain cases, severe disruptions in daily life and even suicidal tendencies. Current drugs for treating PMS, such as selective serotonin reuptake inhibitors, do not yield satisfactory results. Orexin, a neuropeptide produced in the lateral hypothalamus, is garnering attention in the treatment of neurological disorders and is believed to modulate the symptoms of PMS. This paper reviews the advancements in research on sleep disturbances, mood changes, and cognitive impairment caused by PMS, and suggests potential pathways for orexin to address these symptoms. Furthermore, it delves into the role of orexin in the molecular mechanisms underlying PMS. Orexin regulates steroid hormones, and the cyclic fluctuations of estrogen and progesterone play a crucial role in the pathogenesis of PMS. Additionally, orexin also modulates the gamma-aminobutyric acid (GABA) system and the inflammatory response involved in coordinating the mechanism of PMS. Unraveling the role of orexin in the pathogenesis of PMS will not only aid in understanding the etiology of PMS but also hold implications for orexin as a novel target for treating PMS.

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Section: Orexin Inhibited Inflammatory Response To Protect Neuronsmentioning

confidence: 99%

The potential role of the orexin system in premenstrual syndrome

Dong,

Dai,

et al. 2024

Front. Endocrinol.

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“…Subsequently, the rats were depilated, and an incision was made in the lower third of the abdomen to locate the uterus, which was Y-shaped. We then removed both ovaries and sutured the incision [22]. For the sham control group, the operation was the same as the bilateral ovarian ablation, but only fat around the bilateral ovaries was removed.…”

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confidence: 99%

Rutin Treats Perimenopausal Depression Rats through Allopregnanolone Mediated mRNA Expression of Gabra4, Gabrb2 in the Prefrontal Cortex

Gao,

et al. 2024

Preprint

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Objective We determined whether the pathogenesis of perimenopausal depression (PMD) is associated with allopregnanolone (3α,5α-THP, ALLO) mediated GABAA receptors subunits expression changes in different brain regions. Simultaneously, we aimed to investigate the therapeutic efficacy and intervention mechanisms of the flavonoid rutin in treating PMD. Methods The PMD rat model was established by ovariectomy surgery followed by chronic unpredictable mirutin stress processes. ALLO was administered via intraperitoneal injection to increase ALLO levels in PMD rats, while rutin was administered via oral gavage for PMD treatment. Behavioral assessments, including open-fierutin test, sucrose preference test, and forced swimming test, were conducted to evaluate depressive-like behaviors in rats. ELISA was employed to measure the levels of E2, 5-HT, NE, ALLO, and GABA in the serum. Quantitative PCR was used to assess the mRNA expression of Gabra4, Gabrb2, and Gabrd in the prefrontal cortex, hippocampus, hypothalamus, and amygdala. Results The PMD rats exhibited depressive-like behavior, with decreased levels of E2, 5-HT, NE, ALLO, and GABA in the serum. The mRNA expression of Gabra4 and Gabrb2 increased in the prefrontal cortex, hippocampus, and hypothalamus of PMD rats, while Gabrd showed a increase in the hypothalamus and amygdala. ALLO improved depressive-like behavior and increased serum levels of E2, 5-HT, NE, and ALLO in PMD rats. ALLO acted on PMD rats, reduced mRNA expression of Gabra4 and Gabrb2 in the prefrontal cortex, increased mRNA expression of Gabrd in the prefrontal cortex, elevated mRNA expression of Gabra4 and Gabrd in the hippocampus, and decreased Gabrb2 mRNA expression in the hypothalamus.Rutin improved depressive-like behavior in PMD rats, increased serum levels of 5-HT and ALLO, and decreased mRNA expression of Gabra4 and Gabrb2 in the prefrontal cortex. Conclusion ALLO-mediated mRNA expression of Gabra4, Gabrb2 in the prefrontal cortex, and Gabrb2 in the hypothalamus is one of the pathological mechanisms in PMD. ALLO can improve depressive symptoms in PMD rats. Rutin (8.65 mg/kg) exerts a therapeutic effect on PMD by upregulating serum ALLO levels, subsequently downregulating mRNA expression of prefrontal cortex Gabra4 and Gabrb2.

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Involvement of Spinal Neuroplastin 65 in Neuropathic Pain by GABAA Receptor α2 Subunit Regulation

Xu,

Wang,

Jiao

et al. 2024

Anesthesia &Amp; Analgesia

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BACKGROUND: Neuropathic pain (NP) is a highly challenging condition with complex pathological mechanisms, and the spinal gamma aminobutyric acid A receptor receptor plays a crucial role in its progression. Recent studies have revealed a potential interaction between neuroplastin 65 (NP65) and gamma aminobutyric acid A receptor α2 subunit (GABAAR-α2) on the cell surface. We hypothesize that NP65 is involved in the pathogenesis of NP by regulating the level of GABAAR-α2. METHODS: A chronic constrictive injury (CCI) pain model was established in male Sprague-Dawley rats to verify the change in spinal NP65 expression. Alterations in pain behavior and GABAAR-α2 protein expression were observed after intrathecal injection of NP65 overexpressing adeno-associated virus (AAV) in CCI rats. In vitro investigations on Neuroblastoma 2a cells, the effect of NP65 on GABAAR-α2 expression via the calcineurin-nuclear factor of activated T-cell 4 (CaN-NFATc4) signaling pathway was evaluated by manipulating NP65 expression. RESULTS: The expression level of NP65 protein and mRNA in the CCI group were significantly decreased (P < .05; analysis of variance [ANOVA]). After intrathecal injection of NP65, overexpression of AAV and pain behavior in CCI rats were significantly alleviated, and levels of GABAAR-α2 were upregulated. In vitro experiments verified alterations in the expression of GABAAR-α2, CaN, and phosphorylated NFATc4 on the application of NP65 with plasmid or small interfering RNA, respectively. After the application of the specific CaN inhibitor cyclosporine A (CsA), the changes in NP65 expression did not produce subsequent alterations in the expression of GABAAR-α2, CaN, or phosphorylated NFATc4 proteins. CONCLUSIONS: NP65 modulates the level of GABAAR-α2 through the CaN-NFATc4 signaling pathway, which may serve as the underlying mechanism of NP.

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

Cited by 3 publications

References 52 publications

The potential role of the orexin system in premenstrual syndrome

The potential role of the orexin system in premenstrual syndrome

Rutin Treats Perimenopausal Depression Rats through Allopregnanolone Mediated mRNA Expression of Gabra4, Gabrb2 in the Prefrontal Cortex

Involvement of Spinal Neuroplastin 65 in Neuropathic Pain by GABAA Receptor α2 Subunit Regulation

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