REM sleep control during aging in SAM mice: a role for inducible nitric oxide synthase.
Evidence that nitric oxide (NO) is involved in the regulation of rapid-eye-movement sleep (REMS) is supported by recent studies. During aging, NO generation encounters marked changes mainly related to the activation of the inducible NO-synthase (iNOS). To investigate links existing between iNOS and REMS impairments related to aging, we examine the age-related variations occurring in: mRNA and activity of iNOS in brainstem and frontal cortex; sleep parameters under baseline and after treatment by a selective iNOS inhibitor (AMT) in Senescence Accelerated Mice (SAM). SAMR1 (control) mice are a model of aging while SAMP8 are adequate to study neurodegenerative processes. RT-PCR analysis does not reveal significant variation in iNOS mRNA expression in both strains. However, significant age-related increases in iNOS activity occur in SAMR1 but such variation is not observed in SAMP8. In baseline conditions, aging induces a slight increase in slow-wave sleep (SWS) amounts in both groups and deteriorates greatly REMS architecture in SAMP8 compared to SAMR1. AMT reduces REMS amounts for 4-6h after treatment in a dose and age-dependent manner in SAMR1. Almost no changes occur in SAMP8. Data reported suggest that NO derived from iNOS contributes to trigger and maintain REMS during aging.
Colas
Damien
D
Institut National de la Santé et de la Recherche Médicale EA3734, Department of Experimental Medicine, Faculty of Medecine, Claude Bernard University, Lyon Cedex 08 69373, France.
Bezin
Laurent
L
Gharib
Abdallah
A
Morales
Anne
A
Cespuglio
Raymond
R
Sarda
Nicole
N
D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012894:Sleep Stages / Q000235:genetics / Q000502:physiology; D012895:Sleep, REM / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology; D014851:Wakefulness / Q000502:physiology
C488155:3-amino-5-mercapto-1,2,4-triazole; D012333:RNA, Messenger; D014230:Triazoles; D012965:Sodium Chloride; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse