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 (NOS). To investigate links existing between NOS and REMS impairments related to aging, we examine the age-related variations occurring in: mRNA and activity of NOS 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 NOS activity occur in SAMRI 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 RENTS architecture in SAMP8 compared to SAMR1. AMT reduces REMS amounts for 4-6 h after treatment in a dose and age-dependent manner in SAMR1. Almost no changes occur in SAMP8. Data reported suggest that NO derived from NOS contributes to trigger and maintain REMS during aging. (c) 2004 Elsevier Inc. All rights reserved.