Noradrenergic changes and memory loss in aged mice.
The present paper addresses the question of whether a decline of central noradrenergic activity is associated with aging and memory loss in mice. Receptor binding techniques were utilized to compare alpha 2-adrenoceptor density in the brains of aged and young mice. Using [3H]rauwolscine, a selective alpha 2-adrenoceptor antagonist, two membrane binding sites were identified which were differentially affected by age. Whereas the density of high-affinity binding sites was unchanged in aged brain as compared to young controls, there was a significant decrease in the number of low-affinity sites. In a separate study, animals were tested for performance on a step-through inhibitory avoidance task, prior to sacrifice and morphological analysis of the brainstem noradrenergic nucleus locus coeruleus (LC). Aged mice exhibited a significant decrease in task retention as compared to young controls; a small, though non-significant, decline was also observed in the numbers of cells within LC. While young mice exhibited low within-group variance, individual aged animals differed greatly in both LC cell number and behavioral performance. Within the aged population, there was a highly significant correlation between the extent of LC cell loss and the degree of memory impairment. These results provide further evidence for an age-related decline in central noradrenergic function which may contribute to an associated memory loss.
D000375:Aging; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D001933:Brain Stem / Q000502:physiology; D002531:Cerebellum / Q000502:physiology; D002540:Cerebral Cortex / Q000502:physiology; D008125:Locus Coeruleus / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009434:Neural Pathways / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*
D009638:Norepinephrine