Serotonin 5-HT2A and 5-HT6 receptors in the prefrontal cortex of Alzheimer and normal aging patients

Abstract

Background: It has been hypothesized that alterations of the serotonergic system contribute to neuropsychiatric symptoms in Alzheimer disease (AD). Cellular expressions of the two serotonergic receptors 5-HT2A and 5-HT6 have therefore been determined by immunohistochemistry in the prefrontal cortex of patients with AD (n=6) and normal age-matched controls (n = 7).

Results: In normal aging patients, 5-HT2A label was mainly observed in large pyramidal cells, but to a lesser extent also in small pyramidal cells and in stellate cells of cortical layers II-VI. In AD, a similar distribution was observed, but density of positive cells was significantly reduced by 33%. In aging control patients, the 5-HT6 receptor was expressed by pyramidal cells and occasional stellate cells, not only of layers II-V, but also of layer I, where a distinct label was observed in neurons and surrounding fibers. 5-HT6 receptor expression in AD patients had the same pattern, but was significantly decreased by 40%.

Conclusion: Our results indicate that a decline in neurons expressing 5-HT2A, but also 5-HT6 receptors may play a role in the etiopathology of neuropsychiatric symptoms in AD.

Figure 1

5-HT_2A receptor. Immunoreaction for the 5-HT_2A receptor in the prefrontal cortex of a normal aging (a, c) and an Alzheimer patient (b, d), cresyl violet counterstain. Both large pyramidal cells (arrowheads) and small interneurons (arrows) are stained. Note the reduction in labeled cells in the cortex of the Alzheimer patient (b, d). a, b: x200; c, d; x400.

Figure 2

Cell densities. Numerical density of 5-HT_2A and 5-HT₆ receptor immunoreactive neurons in the prefrontal cortex of normal aging (n=7) and Alzheimer (AD) patients (n=6). Depicted are means ± SEM. Significant differences (p ≤ 0.05) are marked by an asterisk (*)

Figure 3

5-HT₆ receptor. 5-HT₆ receptor immunoreactive cells in the prefrontal cortex of normal aging (a, c, d) and Alzheimer patients (b, e), cresyl violet counterstain. Label is observed in large pyramidal cells (arrowhead) and small interneurons (arrow). Note positive cells and dense immunoreactive fibers in the molecular layer (d). In the cortex of the Alzheimer patient (b, e), significantly fewer cells are labeled than in that of the normal aging patient (a, c, d). a, b: x200; c, d, e; x400.