RU486 Reverses Emotional Disorders by Influencing Astrocytes and Endoplasmic Reticulum Stress in Chronic Restraint Stress Challenged Rats

Dong, Liru; Wang, Songjun; Li, Yingmin; Zhao, Ziqin; Shen, Yiwen; Liu, Li; Gao, Xu; Ma, Chunling; Li, Shujin; Zhang, Xiaojing; Cong, Bin

doi:10.1159/000478764

Cited by 20 publications

(11 citation statements)

References 33 publications

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“…In the EPM test, the CRS þ Sham group which exposed to CRS procedure was less tended to enter and spent time in the open arms and both %OAE and %OAT parameters significantly declined compared to the control group. These results are parallel to the prior depression studies [27,28]. In a study by Salehpour et al [20] the anti-anxiety effect of NIR (810 nm, 10 Hz) TPBM in CMS rat was evaluated by EPM test.…”

Section: Discussionsupporting

confidence: 78%

Transcranial photobiomodulation prevents anxiety and depression via changing serotonin and nitric oxide levels in brain of depression model mice: A study of three different doses of 810 nm laser

et al. 2019

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Objectives The effectiveness of transcranial photobiomodulation (TPBM) in treating anxiety and depression disorders is a demonstrated and identified issue. However, the optimum therapeutic dose and the underlying mechanism of action are not fully understood. In this study, the therapeutic effects of three different near‐infrared (NIR) doses on anxiety‐ and depression‐like behaviors as well as cerebral levels of serotonin (5‐HT) and nitric oxide (NO) were evaluated in a mouse model of chronic restraint stress (CRS). Materials and Methods CRS procedure (3 hours/day, over 3 weeks) was performed as a typical stress model to study anxiety and depression along with laser treatment (3 times/week, over 3 weeks), which began simultaneously with CRS. A NIR diode laser (810 nm wavelength, 10 Hz) with the output power of 200 mW and power density of 4.75 W/cm2 was implemented to deliver three different doses of 4, 8, and 16 J/cm2 to the cerebral cortex of mice. Behavioral experiments including open field, tail suspension, and elevated plus maze tests as well as serum cortisol levels were assessed to evaluate the anti‐anxiety and anti‐depressive effects of NIR TPBM. The changes of 5‐HT and NO levels in the prefrontal cortex (PFC) and hippocampus (Hipp) were assessed. Results CRS procedure induced anxiety‐ and depression‐like behaviors, increased serum cortisol levels, decreased 5‐HT and increased NO levels in the PFC and Hipp areas. NIR TPBM improved behavioral results, decreased serum cortisol levels, increased 5‐HT and decreased NO concentrations in the PFC and Hipp. A dose of 8 J/cm2 of NIR TPBM showed the maximum effects on behavioral and molecular results, while a decline was observed from the optimum effects at both lower (4 J/cm2) and higher (16 J/cm2) doses. Conclusion Our results demonstrated that NIR TPBM had an anti‐anxiety and anti‐depressive effect in CRS mice, which is probably linked to increasing 5‐HT and decreasing NO levels in the PFC and Hipp areas. Also, the maximum anti‐anxiety and anti‐depressive effect was produced at dose of 8 J/cm2. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 78%

Transcranial photobiomodulation prevents anxiety and depression via changing serotonin and nitric oxide levels in brain of depression model mice: A study of three different doses of 810 nm laser

et al. 2019

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“…At the used dose and injection volume, mifepristone is characterized by poor solubility in aqueous vehicles. To improve the solubility, 100% propylene glycol [45] was slowly added to the compound while mixing with a magnetic stir bar. The 60 mg/kg dose and 90 min pretreatment were chosen based on previously published reports demonstrating that the acute systemic administration of this dose of mifepristone reduces alcohol reinforcement [21], and doses ranging between 20 mg/kg and 120 mg/kg have an anxiolytic effect in male rats [35,36].…”

Section: Drug Preparation and Treatmentmentioning

confidence: 99%

Glucocorticoid Receptor Antagonist Mifepristone Does Not Alter Innate Anxiety-Like Behavior in Genetically-Selected Marchigian Sardinian (msP) Rats

Vozella

Cruz

Natividad³

et al. 2021

IJMS

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Marchigian Sardinian alcohol-preferring (msP) rats serve as a unique model of heightened alcohol preference and anxiety disorders. Their innate enhanced stress and poor stress-coping strategies are driven by a genetic polymorphism of the corticotropin-releasing factor receptor 1 (CRF1) in brain areas involved in glucocorticoid signaling. The activation of glucocorticoid receptors (GRs) regulates the stress response, making GRs a candidate target to treat stress and anxiety. Here, we examined whether mifepristone, a GR antagonist known to reduce alcohol drinking in dependent rats, decreases innate symptoms of anxiety in msPs. Male and female msPs were compared to non-selected Wistar counterparts across three separate behavioral tests. We assessed anxiety-like behavior via the novelty-induced hypophagia (NIH) assay. Since sleep disturbances and hyperarousal are common features of stress-related disorders, we measured sleeping patterns using the comprehensive lab monitoring system (CLAMS) and stress sensitivity using acoustic startle measures. Rats received an acute administration of vehicle or mifepristone (60 mg/kg) 90 min prior to testing on NIH, acoustic startle response, and CLAMS. Our results revealed that both male and female msPs display greater anxiety-like behaviors as well as enhanced acoustic startle responses compared to Wistar counterparts. Male msPs also displayed reduced sleeping bout duration versus Wistars, and female msPs displayed greater acoustic startle responses versus male msPs. Importantly, the enhanced anxiety-like behavior and startle responses were not reduced by mifepristone. Together, these findings suggest that increased expression of stress-related behaviors in msPs are not solely mediated by acute activation of GRs.

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“…Several studies have revealed restraint stress could induce atrophy of glutamatergic pyramidal neurons in the amygdala, potentially leading to mental disorders (Padival et al, 2013; Grillo et al, 2015). Our previous study has also suggested restraint stress to be linked with degeneration of amygdalar neurons and astrocytes in rats and induce behavioral changes, such as anxiety and depression (Dong et al, 2017). Nevertheless, the specific mechanisms underlying these phenomena remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Restraint Stress Induced Hyperpermeability and Damage of the Blood-Brain Barrier in the Amygdala of Adult Rats

Gao

et al. 2019

Front. Mol. Neurosci.

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Intense or prolonged exposure to stress can damage various brain structures, including the amygdala and hippocampus, which are associated with emotional-cognitive functions. Furthermore, this deterioration has been linked to a myriad of neurodegenerative and psychiatric disorders, in particular through disruption of the blood-brain barrier (BBB). However, insights remain scarce concerning the effects and mechanisms associated with stress on the BBB in the amygdala. This study explored the effects of restraint stress on the permeability and integrity of the BBB in the amygdala of male adult SD rats. Serum levels of corticosterone (CORT) and S100B were determined through ELISA. The permeability of the BBB was assessed by measuring Evans Blue (EB) leakage in tissue samples from the rats’ amygdala. These samples were immunostained for markers of tight junctions (Claudin-5, Occludin, ZO-1) and adherens junctions (VE-cadherin), as well as GLUT-1 and AQP-4. Staining was evaluated through confocal microscopy, and the level of expression of these proteins was quantified using the Western Blot (WB) technique. The ultrastructure of brain microvascular endothelial cells was assessed with transmission electron microscopy. Moreover, interleukin-1 beta (IL-1β) content in serum and amygdalar tissues were determined by employing ELISA. Exposure to restraint stress was associated with higher serum levels of S100B and EB leakage in amygdala tissues, especially in days 14 and 21 of the experiment, indicating increased permeability of the BBB. After restraint stress, significant decreases in protein expression were detected for tight junctions, adherens junctions and GLUT-1, while a significant increase was observed for AQP-4. The variation trends of fluorescence intensity generally paralleled these results. Following restraint stress, transmission electron microscopy ascertained enlarged gaps in tight junctions and thickened basal membranes in amygdalar capillaries. In addition, increased IL-1β contents in serum and amygdalar tissues were observed in the restraint-stressed groups. These findings suggest that restraint stress mediates time-dependent alterations in the permeability of the BBB, with modifications in the expression of proteins from tight junctions and adherens junctions, as well as ultrastructural changes in brain microvascular endothelial cells. And it was associated with the inflammation. These alterations may be associated with behavioral and cognitive dysfunctions and neurodegenerative disorders.

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RU486 Reverses Emotional Disorders by Influencing Astrocytes and Endoplasmic Reticulum Stress in Chronic Restraint Stress Challenged Rats

Cited by 20 publications

References 33 publications

Transcranial photobiomodulation prevents anxiety and depression via changing serotonin and nitric oxide levels in brain of depression model mice: A study of three different doses of 810 nm laser

Transcranial photobiomodulation prevents anxiety and depression via changing serotonin and nitric oxide levels in brain of depression model mice: A study of three different doses of 810 nm laser

Glucocorticoid Receptor Antagonist Mifepristone Does Not Alter Innate Anxiety-Like Behavior in Genetically-Selected Marchigian Sardinian (msP) Rats

Restraint Stress Induced Hyperpermeability and Damage of the Blood-Brain Barrier in the Amygdala of Adult Rats

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