| First Author | Cirrito JR | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 36 | Pages | 14968-73 |
| PubMed ID | 21873225 | Mgi Jnum | J:175216 |
| Mgi Id | MGI:5284996 | Doi | 10.1073/pnas.1107411108 |
| Citation | Cirrito JR, et al. (2011) Serotonin signaling is associated with lower amyloid-{beta} levels and plaques in transgenic mice and humans. Proc Natl Acad Sci U S A 108(36):14968-73 |
| abstractText | Aggregation of amyloid-beta (Abeta) as toxic oligomers and amyloid plaques within the brain appears to be the pathogenic event that initiates Alzheimer's disease (AD) lesions. One therapeutic strategy has been to reduce Abeta levels to limit its accumulation. Activation of certain neurotransmitter receptors can regulate Abeta metabolism. We assessed the ability of serotonin signaling to alter brain Abeta levels and plaques in a mouse model of AD and in humans. In mice, brain interstitial fluid (ISF) Abeta levels were decreased by 25% following administration of several selective serotonin reuptake inhibitor (SSRI) antidepressant drugs. Similarly, direct infusion of serotonin into the hippocampus reduced ISF Abeta levels. Serotonin-dependent reductions in Abeta were reversed if mice were pretreated with inhibitors of the extracellular regulated kinase (ERK) signaling cascade. Chronic treatment with an SSRI, citalopram, caused a 50% reduction in brain plaque load in mice. To test whether serotonin signaling could impact Abeta plaques in humans, we retrospectively compared brain amyloid load in cognitively normal elderly participants who were exposed to antidepressant drugs within the past 5 y to participants who were not. Antidepressant-treated participants had significantly less amyloid load as quantified by positron emission tomography (PET) imaging with Pittsburgh Compound B (PIB). Cumulative time of antidepressant use within the 5-y period preceding the scan correlated with less plaque load. These data suggest that serotonin signaling was associated with less Abeta accumulation in cognitively normal individuals. |
