Presynaptic markers of cholinergic function in the rat brain: relationship with age and cognitive status. Neuroscience 1999 Mar;89(3):771-9
Date
04/13/1999Pubmed ID
10199612DOI
10.1016/s0306-4522(98)00374-1Scopus ID
2-s2.0-0032915465 (requires institutional sign-in at Scopus site) 53 CitationsAbstract
The nature of age-related changes in cholinergic function and their relationship to age-related behavioral decline were examined in the present study. Male Fischer-344 rats of four ages (four, 11, 17 and 23 months) were tested in a battery of cognitive tasks. Discrete microdissections of brain areas involved in cognitive function were performed, and activity of choline acetyltransferase and levels of hemicholinium-3 binding were determined to assess the integrity of cholinergic innervation. Age-related changes in cholinergic markers occurred predominantly in the medial septal area and its target areas (hippocampus and cingulate cortex), and were also present in the posterior caudate. However, most of the age-related changes in cholinergic markers were already present at ages at which behavioral impairment was not yet maximal. There were some consistent correlations between behavioral and neurochemical measures, independent of age, but these accounted for relatively small proportions of variance in behavioral performance. For most of these correlations, lower levels of presynaptic cholinergic markers were related to better behavioral performance. In brain areas in which correlations changed with age, lower levels of presynaptic cholinergic markers were associated with better performance in young rats, whereas higher levels were associated with better performance in aged rats. Recent lesion studies using a toxin selective for basal forebrain cholinergic neurons have suggested that these neurons do not play as central a role in learning and memory in young and aged animals as was previously thought. When considered in this context, the present results suggest that preserved cholinergic function in old age might act indirectly to sustain cognitive ability. Changes in cholinergic function may represent one of a number of age-related neurobiological events that underlie behavioral impairments, or may be a permissive factor for other age-related processes that are more directly responsible for cognitive impairments.
Author List
Baxter MG, Frick KM, Price DL, Breckler SJ, Markowska AL, Gorman LKAuthor
Karyn Frick BA,MA,PhD Professor in the Psychology department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
AcetylcholineAging
Animals
Biomarkers
Brain Chemistry
Choline O-Acetyltransferase
Cholinergic Agents
Cognition
Cognition Disorders
Hemicholinium 3
Male
Maze Learning
Memory
Nerve Tissue Proteins
Organ Specificity
Rats
Rats, Inbred F344
Receptors, Presynaptic
