Regional age-related changes in neuronal nitric oxide synthase (nNOS), messenger RNA levels and activity in SAMP8 brain

We found that the levels of nNOS mRNA decreased in the cortex and the hippocampus of 8- vs 2-month-old animals followed by an increase in 12-vs 8-month-old animals in both strains. In the brainstem, levels of nNOS mRNA decreased in an age-dependent manner in SAMP8, but not in SAMR1. Regional age-related changes were also observed in nNOS activity. Moreover, nNOS activity in hippocampus was found lower in 8-month-old SAMP8 than in SAMR1, while in the cortex and the brainstem, nNOS activities increased at 8 months and afterward decreased with age in SAMP8 and SAMR1. NOx- levels showed profiles similar to nNOS activities in the cortex and the brainstem but were undetectable in the hippocampus of SAMP8 and SAMR1. Finally, NOx- levels were higher in the cortex of 8 month-old SAMP8 than in age-matched SAMR1.Concomitant variations occurring in NO levels derived from nNOS and iNOS at an early age constitute a major factor of risk for sleep and/or memory impairments in SAMP8.Aging is defined by an increase in the probability of death over time associated with characteristic changes in phenotype [1]. Sleep alteration is a common phenomenon observed in humans and animals during aging and is often associated with impaired learning and memory [2]. The oxidative stress resulting from the loss of control of reactive oxygen species (ROS) and the production of nitric oxide (NO), when produced in excess and not balanced by antioxidants, represent an attractive process responsible, at least partially, for the above impairments during aging or related disorders such as Alzheimer disease (AD) [3]. Our recent data obtained in aged rats [4] and in senescence accelerated prone 8 mice (SAMP8) [5], a model of early onset of human diseases [6], support such an hypothesis.NO is an intracellular multifunctional molecule involved in both physiological and neurodegenerative processes of the CNS. The dynamic of the NO release taking place in the thalamus and the cortex [7,8] and/or locally in the