Sex-Dependent Effects of Piromelatine Treatment on Sleep-Wake Cycle and Sleep Structure of Prenatally Stressed Rats
Prenatal stress (PNS) impairs the circadian rhythm of the sleep/wake cycle. The melatonin (MT) analogue Piromelatine (Pir) was designed for the treatment of insomnia. The present study aimed to explore effects of Pir on circadian rhythmicity, motor activity, and sleep structure in male and female ra...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| author | Jana Tchekalarova Lidia Kortenska Pencho Marinov Natasha Ivanova |
| author_facet | Jana Tchekalarova Lidia Kortenska Pencho Marinov Natasha Ivanova |
| author_sort | Jana Tchekalarova |
| collection | DOAJ |
| description | Prenatal stress (PNS) impairs the circadian rhythm of the sleep/wake cycle. The melatonin (MT) analogue Piromelatine (Pir) was designed for the treatment of insomnia. The present study aimed to explore effects of Pir on circadian rhythmicity, motor activity, and sleep structure in male and female rats with a history of prenatal stress (PNS). In addition, we elucidated the role of MT receptors and brain-derived neurotrophic factor (BDNF) to ascertain the underlying mechanism of the drug. Pregnant rats were exposed to different stressors from day seven until birth. Piromelatine (20 mg/kg/day/14 days) was administered to young adult offspring. Home-cage locomotion, electroencephalographic (EEG) and electromyographic (EMG) recordings were conducted for 24 h. Offspring treated with vehicle showed sex-and phase-dependent disturbed circadian rhythm of motor activity and sleep/wake cycle accompanied by elevated rapid eye movement (REM) pattern and <i>theta</i> power and diminished non-rapid eye movement (NREM) sleep and <i>delta</i> power. While Pir corrected the PNS-induced impaired sleep patterns, the MT receptor antagonist luzindol suppressed its effects in male and female offspring. In addition, Pir increased the BDNF expression in the hippocampus in male and female offspring with PNS. Our findings suggest that the beneficial effect of Pir on PNS-induced impairment of sleep/wake cycle circadian rhythm and sleep structure is exerted via activation of MT receptors and enhanced BDNF expression in the hippocampus in male and female offspring. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:47:29Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-27ea49a5d6114d7e9d1728613af32f9a2023-11-23T16:40:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181034910.3390/ijms231810349Sex-Dependent Effects of Piromelatine Treatment on Sleep-Wake Cycle and Sleep Structure of Prenatally Stressed RatsJana Tchekalarova0Lidia Kortenska1Pencho Marinov2Natasha Ivanova3Institute of Neurobiology, Bulgarian Academy of Sciences (BAS), 1113 Sofia, BulgariaInstitute of Neurobiology, Bulgarian Academy of Sciences (BAS), 1113 Sofia, BulgariaInstitute of Information and Communication Technologies, Bulgarian Academy of Sciences (BAS), 1113 Sofia, BulgariaInstitute of Neurobiology, Bulgarian Academy of Sciences (BAS), 1113 Sofia, BulgariaPrenatal stress (PNS) impairs the circadian rhythm of the sleep/wake cycle. The melatonin (MT) analogue Piromelatine (Pir) was designed for the treatment of insomnia. The present study aimed to explore effects of Pir on circadian rhythmicity, motor activity, and sleep structure in male and female rats with a history of prenatal stress (PNS). In addition, we elucidated the role of MT receptors and brain-derived neurotrophic factor (BDNF) to ascertain the underlying mechanism of the drug. Pregnant rats were exposed to different stressors from day seven until birth. Piromelatine (20 mg/kg/day/14 days) was administered to young adult offspring. Home-cage locomotion, electroencephalographic (EEG) and electromyographic (EMG) recordings were conducted for 24 h. Offspring treated with vehicle showed sex-and phase-dependent disturbed circadian rhythm of motor activity and sleep/wake cycle accompanied by elevated rapid eye movement (REM) pattern and <i>theta</i> power and diminished non-rapid eye movement (NREM) sleep and <i>delta</i> power. While Pir corrected the PNS-induced impaired sleep patterns, the MT receptor antagonist luzindol suppressed its effects in male and female offspring. In addition, Pir increased the BDNF expression in the hippocampus in male and female offspring with PNS. Our findings suggest that the beneficial effect of Pir on PNS-induced impairment of sleep/wake cycle circadian rhythm and sleep structure is exerted via activation of MT receptors and enhanced BDNF expression in the hippocampus in male and female offspring.https://www.mdpi.com/1422-0067/23/18/10349prenatal stresssexpiromelatinemotor activitysleep/wake cycleBDNF |
| spellingShingle | Jana Tchekalarova Lidia Kortenska Pencho Marinov Natasha Ivanova Sex-Dependent Effects of Piromelatine Treatment on Sleep-Wake Cycle and Sleep Structure of Prenatally Stressed Rats International Journal of Molecular Sciences prenatal stress sex piromelatine motor activity sleep/wake cycle BDNF |
| title | Sex-Dependent Effects of Piromelatine Treatment on Sleep-Wake Cycle and Sleep Structure of Prenatally Stressed Rats |
| title_full | Sex-Dependent Effects of Piromelatine Treatment on Sleep-Wake Cycle and Sleep Structure of Prenatally Stressed Rats |
| title_fullStr | Sex-Dependent Effects of Piromelatine Treatment on Sleep-Wake Cycle and Sleep Structure of Prenatally Stressed Rats |
| title_full_unstemmed | Sex-Dependent Effects of Piromelatine Treatment on Sleep-Wake Cycle and Sleep Structure of Prenatally Stressed Rats |
| title_short | Sex-Dependent Effects of Piromelatine Treatment on Sleep-Wake Cycle and Sleep Structure of Prenatally Stressed Rats |
| title_sort | sex dependent effects of piromelatine treatment on sleep wake cycle and sleep structure of prenatally stressed rats |
| topic | prenatal stress sex piromelatine motor activity sleep/wake cycle BDNF |
| url | https://www.mdpi.com/1422-0067/23/18/10349 |
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