Effect of N-Acetylcysteine on Sleep: Impacts of Sex and Time of Day
Non-rapid eye movement sleep (NREMS) is accompanied by a decrease in cerebral metabolism, which reduces the consumption of glucose as a fuel source and decreases the overall accumulation of oxidative stress in neural and peripheral tissues. Enabling this metabolic shift towards a reductive redox env...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/12/5/1124 |
| _version_ | 1797601252056498176 |
|---|---|
| author | Priyanka N. Bushana Michelle A. Schmidt Kevin M. Chang Trisha Vuong Barbara A. Sorg Jonathan P. Wisor |
| author_facet | Priyanka N. Bushana Michelle A. Schmidt Kevin M. Chang Trisha Vuong Barbara A. Sorg Jonathan P. Wisor |
| author_sort | Priyanka N. Bushana |
| collection | DOAJ |
| description | Non-rapid eye movement sleep (NREMS) is accompanied by a decrease in cerebral metabolism, which reduces the consumption of glucose as a fuel source and decreases the overall accumulation of oxidative stress in neural and peripheral tissues. Enabling this metabolic shift towards a reductive redox environment may be a central function of sleep. Therefore, biochemical manipulations that potentiate cellular antioxidant pathways may facilitate this function of sleep. N-acetylcysteine increases cellular antioxidant capacity by serving as a precursor to glutathione. In mice, we observed that intraperitoneal administration of N-acetylcysteine at a time of day when sleep drive is naturally high accelerated the onset of sleep and reduced NREMS delta power. Additionally, N-acetylcysteine administration suppressed slow and beta electroencephalographic (EEG) activities during quiet wake, further demonstrating the fatigue-inducing properties of antioxidants and the impact of redox balance on cortical circuit properties related to sleep drive. These results implicate redox reactions in the homeostatic dynamics of cortical network events across sleep/wake cycles, illustrating the value of timing antioxidant administration relative to sleep/wake cycles. A systematic review of the relevant literature, summarized herein, indicates that this “chronotherapeutic hypothesis” is unaddressed within the clinical literature on antioxidant therapy for brain disorders such as schizophrenia. We, therefore, advocate for studies that systematically address the relationship between the time of day at which an antioxidant therapy is administered relative to sleep/wake cycles and the therapeutic benefit of that antioxidant treatment in brain disorders. |
| first_indexed | 2024-03-11T03:59:28Z |
| format | Article |
| id | doaj.art-48c6fc34da894365bb456f95b88954eb |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T03:59:28Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-48c6fc34da894365bb456f95b88954eb2023-11-18T00:15:58ZengMDPI AGAntioxidants2076-39212023-05-01125112410.3390/antiox12051124Effect of N-Acetylcysteine on Sleep: Impacts of Sex and Time of DayPriyanka N. Bushana0Michelle A. Schmidt1Kevin M. Chang2Trisha Vuong3Barbara A. Sorg4Jonathan P. Wisor5Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USAElson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USAElson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USAElson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USAR.S. Dow Neurobiology Laboratories, Legacy Research Institute, Portland, OR 97232, USAElson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USANon-rapid eye movement sleep (NREMS) is accompanied by a decrease in cerebral metabolism, which reduces the consumption of glucose as a fuel source and decreases the overall accumulation of oxidative stress in neural and peripheral tissues. Enabling this metabolic shift towards a reductive redox environment may be a central function of sleep. Therefore, biochemical manipulations that potentiate cellular antioxidant pathways may facilitate this function of sleep. N-acetylcysteine increases cellular antioxidant capacity by serving as a precursor to glutathione. In mice, we observed that intraperitoneal administration of N-acetylcysteine at a time of day when sleep drive is naturally high accelerated the onset of sleep and reduced NREMS delta power. Additionally, N-acetylcysteine administration suppressed slow and beta electroencephalographic (EEG) activities during quiet wake, further demonstrating the fatigue-inducing properties of antioxidants and the impact of redox balance on cortical circuit properties related to sleep drive. These results implicate redox reactions in the homeostatic dynamics of cortical network events across sleep/wake cycles, illustrating the value of timing antioxidant administration relative to sleep/wake cycles. A systematic review of the relevant literature, summarized herein, indicates that this “chronotherapeutic hypothesis” is unaddressed within the clinical literature on antioxidant therapy for brain disorders such as schizophrenia. We, therefore, advocate for studies that systematically address the relationship between the time of day at which an antioxidant therapy is administered relative to sleep/wake cycles and the therapeutic benefit of that antioxidant treatment in brain disorders.https://www.mdpi.com/2076-3921/12/5/1124electroencephalographysleepantioxidantsschizophreniaN-acetylcysteine |
| spellingShingle | Priyanka N. Bushana Michelle A. Schmidt Kevin M. Chang Trisha Vuong Barbara A. Sorg Jonathan P. Wisor Effect of N-Acetylcysteine on Sleep: Impacts of Sex and Time of Day Antioxidants electroencephalography sleep antioxidants schizophrenia N-acetylcysteine |
| title | Effect of N-Acetylcysteine on Sleep: Impacts of Sex and Time of Day |
| title_full | Effect of N-Acetylcysteine on Sleep: Impacts of Sex and Time of Day |
| title_fullStr | Effect of N-Acetylcysteine on Sleep: Impacts of Sex and Time of Day |
| title_full_unstemmed | Effect of N-Acetylcysteine on Sleep: Impacts of Sex and Time of Day |
| title_short | Effect of N-Acetylcysteine on Sleep: Impacts of Sex and Time of Day |
| title_sort | effect of n acetylcysteine on sleep impacts of sex and time of day |
| topic | electroencephalography sleep antioxidants schizophrenia N-acetylcysteine |
| url | https://www.mdpi.com/2076-3921/12/5/1124 |
| work_keys_str_mv | AT priyankanbushana effectofnacetylcysteineonsleepimpactsofsexandtimeofday AT michelleaschmidt effectofnacetylcysteineonsleepimpactsofsexandtimeofday AT kevinmchang effectofnacetylcysteineonsleepimpactsofsexandtimeofday AT trishavuong effectofnacetylcysteineonsleepimpactsofsexandtimeofday AT barbaraasorg effectofnacetylcysteineonsleepimpactsofsexandtimeofday AT jonathanpwisor effectofnacetylcysteineonsleepimpactsofsexandtimeofday |