Presynaptic markers of cholinergic function in the rat brain: relationship with age and cognitive status
Section snippets
Subjects
Male Fischer-344 rats were obtained from the National Institute of Aging colony at Harlan. At the beginning of behavioral testing, the rats were four, 11, 17 or 23 months old (n=18 per group) and were housed two to three per cage in a temperature- and humidity-controlled colony room on a 12-h/12-h light/dark cycle. Behavioral testing was performed during the light portion of the cycle. Food and water were available ad libitum. Behavioral testing began approximately one week after the rats
Results
Low protein levels precluded determination of both ChAT activity and HC-3 binding in some samples. These missing points were relatively homogeneously distributed with respect to age and behavioral status. Because the microdissection procedure used resulted in small pieces of tissue, a substantial amount of variability was present in some neurochemical measures. In order to reduce overall variability, an initial screening removed data-points falling more than two standard deviations from the
Discussion
The results of this study demonstrated significant effects of age on presynaptic markers of cholinergic function as measured by ChAT activity and HC-3 binding. These changes were found predominantly in areas containing cholinergic cell bodies (the medial septal area and posterior caudate) and in target areas of the medial septal area (the hippocampus and cingulate cortex). Markers of presynaptic cholinergic function in some anatomical areas were reliably correlated with behavioral performance,
Conclusions
Although changes in the cholinergic system are most likely not the direct cause of age-related impairments in behavior, they may play a permissive role in the development of other neurobiological changes that are more directly linked to behavioral impairment. Although this study was conducted in a cross-sectional rather than a longitudinal fashion, the data suggest that alterations in cholinergic function precede the development of cognitive impairment. Loss of cholinergic function earlier in
Acknowledgements
We thank Dr Molly V. Wagster for her contributions to this research, and Karena P. Joung and Joyce A. Kotzuk for technical assistance. This research was supported by NIH Grant P50-NS20471 to D.L.P. Dr Linda K. Gorman would like to respectfully remember the contributions of Dr David Olton to this work.
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