Serotonin-2B receptor (5-HT 2B R) expression and binding in the brain of APP swe /PS1 dE9 transgenic mice and in Alzheimer's disease brain tissue

Despite well-documented dysregulation in central serotonergic signaling in Alzheimer's disease (AD), knowledge about the potential involvement of the serotonin-2B receptor (5-HT R) subtype remains sparse. Here, we assessed the levels of 5-HT Rs in brain tissue from APP /PS1 transgenic (TG) mice, AD patients, and adult microglial cells. 5-HT R mRNA was measured by RT-qPCR in ageing TG and wild-type (WT) mice, in samples from the middle frontal gyrus of female, AD and control subjects, and in microglia from the cerebral cortex of WT mice. The density of 5-HT Rs was measured by autoradiography using [ H]RS 127445. Both mouse and human brains had low levels of 5-HT R mRNA. In whole-brain mouse samples, mRNA expression was significantly lower in TG mice compared to WT at > 18 months of age. In the Aβ-plaque-burdened neocortex and hippocampus of old TG mice, however, levels of 5-HT R mRNA were two-fold higher over control, with similar elevations observed in the Aβ-plaque-burdened frontal cortex of human AD patients. 5-HT R mRNA expression varied widely in adult microglia and was higher compared to other cortical cell subtypes. In mice, specific [ H]RS-127445 binding in the cortex was first detected after 3 months of age. The density of 5-HT Rs was low and overall reduced in TG, compared to WT mice. Binding was detectable but too low to be reliably quantified in the human cortex. Our results document Aβ-associated increases in 5-HT R mRNA expression and suggest reduced receptor binding in the context of AD. Studies investigating the functional involvement of microglial 5-HT Rs in AD are considered relevant.