Serotonin-2B receptor (5-HT2BR) expression and binding in the brain of APPswe/PS1dE9 transgenic mice and in Alzheimer’s disease brain tissue

• Published in: Neuroscience letters Vol. 844; p. 138013
• Main Authors: Anzalone, Marco, Karam, Sarmad A., Briting, Sanne R.R., Petersen, Sussanne, Thomsen, Majken B., Babcock, Alicia A., Landau, Anne M., Finsen, Bente, Metaxas, Athanasios
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.01.2025
• Subjects: 5-HT2B; Alzheimer; APPswe/PS1dE9; Autoradiography; Microglia; PCR; Serotonin; Autoradiography; Serotonin; 5-HT2B; Alzheimer; PCR; APPswe/PS1dE9; Microglia
• ISSN: 0304-3940; 1872-7972; 1872-7972
• DOI: 10.1016/j.neulet.2024.138013

Despite well-documented dysregulation in central serotonergic signaling in Alzheimer’s disease (AD), knowledge about the potential involvement of the serotonin-2B receptor (5-HT2BR) subtype remains sparse. Here, we assessed the levels of 5-HT2BRs in brain tissue from APPswe/PS1dE9 transgenic (TG) mice, AD patients, and adult microglial cells. 5-HT2BR 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-HT2BRs was measured by autoradiography using [3H]RS 127445. Both mouse and human brains had low levels of 5-HT2BR 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-HT2BR mRNA were two-fold higher over control, with similar elevations observed in the Aβ-plaque-burdened frontal cortex of human AD patients. 5-HT2BR mRNA expression varied widely in adult microglia and was higher compared to other cortical cell subtypes. In mice, specific [3H]RS-127445 binding in the cortex was first detected after 3 months of age. The density of 5-HT2BRs 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-HT2BR mRNA expression and suggest reduced receptor binding in the context of AD. Studies investigating the functional involvement of microglial 5-HT2BRs in AD are considered relevant.