Mifepristone reduces hypothalamo-pituitary-adrenal axis activation and restores weight loss in rats subjected to dietary restriction and methylphenidate administration

Khalil, Rami Bou; Smayra, Viviane; Saliba, Youakim; Hajal, Joelle; Bakhos, Jules-Joël; Souaiby, Lama; Richa, Sami; Tamraz, J.; Farès, Nassim

doi:10.1016/j.neures.2017.12.008

Cited by 2 publications

(3 citation statements)

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“…Mifepristone, a GR antagonist, was approved by the United States Food and Drug Administration in 2012 for treating patients with hyperglycemia secondary to Cushing’s syndrome 37 and has been reported to reduce HPA axis activation and restore weight through adipose tissue recovery. 38 In the present study, variables including swimming distance, number of times of reaching the platform, expression of GR mRNA in the hypothalami, and serum levels of CRH, ACTH, and CORT were significantly improved following mifepristone treatment compared with control, which was consistent with previous reports. 42 Similar results were found for rats treated with HQ decoction (hT-hH-HQ group).…”

Section: Discussionsupporting

confidence: 92%

“…All rats were randomly assigned into 4 groups (10 rats per group): rats without stress (control group); rats induced with hT and hH (hT-hH group); rats induced with hT and hH and treated with HQ decoction (hT-hH-HQ group); and rats induced with hT and hH and treated with mifepristone (C29H35NO2) (hT-hH-Mi group). Mifepristone, a GR antagonist and a regulator of the function of the HPA axis, 37,38 was used as a control in the hT-hH-Mi group. Treatments and humidity and temperature conditions were as follows.…”

Section: Methodsmentioning

confidence: 99%

“…This study was conducted to investigate the effect of HQ decoction on the HPA axis in rats exposed to hH and hT for 3 weeks in comparison with the effect of mifepristone, a GR antagonist and regulator of HPA axis function. 37,38 The cognitive ability of stressed rats was evaluated using the Morris water maze test and open-field test. The pathologic phenotype, expression of GR mRNA in rat hypothalami, and circulating secretion of hormones related the HPA axis were also assessed (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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Huang Qin Hua Shi decoction for high-temperature- and high-humidity-induced cognitive-behavioral disorder in rats is associated with deactivation of the hypothalamic–pituitary–adrenal axis

Luo¹,

Guo²,

Zhong³

et al. 2019

J Int Med Res

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ObjectiveTo investigate the effects of Huang Qin Hua Shi (HQ) decoction on the hypothalamic–pituitary–adrenal (HPA) axis in rats under high-temperature (hT)- and high-humidity (hH)-induced stress.MethodsMale rats were randomized into four groups: rats without stress; rats induced with hT (35 ± 1°C) and hH (85 ± 5% humidity); rats induced with hT and hH and treated with HQ decoction; and rats induced with hT and hH and treated with mifepristone. After 3 weeks, rats underwent the Morris water maze and open-field test. Rat hypothalami were analyzed pathologically using hematoxylin and eosin staining and glucocorticoid receptor (GR) mRNA expression was evaluated by in situ hybridization. Serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosteroid (CORT) were assessed by enzyme-linked immunosorbent assay.ResultsThe administration of mifepristone or HQ in stressed rats significantly improved their performance in the Morris water maze test and increased the central-to-peripheral ratio and incidence of deep rearing in the open-field test. Mifepristone and HQ also reversed histological changes in the hypothalami of stressed rats. Compared with control rats, GR mRNA expression in the hypothalamus and serum CRH, ACTH, and CORT were significantly elevated in rats stressed with hT and hH, and these changes were attenuated by mifepristone and HQ.ConclusionHQ decoction protects against hT- and hH-induced cognitive-behavioral disorder and its therapeutic effect is associated with decreased HPA axis activity.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%