title: Active sleep and its role in the prevention of apoptosis in the developing brain.
abstract: The aim of this study is to identify a possible function of Active Sleep (AS), also known as Rapid Eye Movement Sleep (REM) in humans, as a protective state during early Central Nervous System (CNS) development. Previous research suggest pharmacological agents that inhibit high levels of neuronal activity in the CNS (e.g., benzodiazepines, ethanol, and anesthetics) precipitate massive CNS programmed cell death (PCD), in developing mammals. AS is characterized by high levels of CNS activity at levels comparable to waking. AS occupies up to 75% of the circadian cycle in developing mammals (rodents from postnatal days 1-14 days (p1-p14), and humans from prenatal month seven to postnatal year one). Many studies have implicated AS as having an active role in the normal development of the visual system and have documented myriad behavioral anomalies as a result of AS deprivation. Reduced adult brain mass has also been observed after AS deprivation in developing rats during this period, however, no study to date has documented this process as it occurs (i.e., the cellular mechanisms that result in behavioral anomalies or reduced adult brain mass). The purpose of this study is to begin documentation of this process by utilizing histological techniques that identify the PCD process, if it occurs, after acute and prolonged AS deprivation in rats from ages p7 to p14 (a time of active synaptogenesis). Our methodology includes utilization of the alpha2-adrenergic receptor agonist clonidine, to deprive rat pups of AS at ages varying from p7 to p14. Pilot data from our laboratory has shown that an acute exposure to clonidine significantly reduces time spent in AS. The animals that were AS deprived also showed a statistically significant decrease in brain mass and have stained positively for PCD. If our hypotheses are correct, this research will have major implications with regard to determining the function(s) of REM sleep.
authors.affiliation: Washington University Sleep Medicine Center, 212 N. Kingshighway Blvd. Suite 1029, Saint Louis, Mo 63108, USA. morrismj@slu.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morrissey
authors.forename: S P
authors.initials: SP
authors.lastname: Duntley
authors.forename: A M
authors.initials: AM
authors.lastname: Anch
authors.forename: R
authors.initials: R
authors.lastname: Nonneman
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000196:embryology / Q000254:growth & development*; D002490:Central Nervous System / Q000254:growth & development; D002940:Circadian Rhythm; D003000:Clonidine / Q000494:pharmacology; D004569:Electroencephalography; D004576:Electromyography; D051381:Rats; D012890:Sleep; D012895:Sleep, REM; D013997:Time Factors; D014851:Wakefulness
chemical_list: D003000:Clonidine