Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/ijms22083919
Keywords
antipsychotic; risperidone; older person; lipid metabolism; sphingolipid; lysophospholipid
Funding
- Ministerio de Ciencia e Innovacion, Spain [SAF2015-70747-R, RTI2018-098113-B-I00, PI18/01152]
- European Regional Development Fund
- Comunidad de Madrid (CAM) [PEJD-2017-PRE/BMD-4142, PEJD-2019-PRE/BMD-15962, PEJD-2019-PRE/SAL-16152]
- Consejeria de Sanidad (CAM)
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After treatment with risperidone, levels of certain lipids in PBMCs of older patients decreased, while lipid raft domains in the plasma membrane were disrupted, potentially affecting multiple signaling pathways associated with these membrane domains.
Atypical or second-generation antipsychotics are used in the treatment of psychosis and behavioral problems in older persons with dementia. However, these pharmaceutical drugs are associated with an increased risk of stroke in such patients. In this study, we evaluated the effects of risperidone treatment on phospholipid and sphingolipid composition and lipid raft function in peripheral blood mononuclear cells (PBMCs) of older patients (mean age >88 years). The results showed that the levels of dihydroceramides, very-long-chain ceramides, and lysophosphatidylcholines decreased in PBMCs of the risperidone-treated group compared with untreated controls. These findings were confirmed by in vitro assays using human THP-1 monocytes. The reduction in the levels of very-long-chain ceramides and dihydroceramides could be due to the decrease in the expression of fatty acid elongase 3, as observed in THP-1 monocytes. Moreover, risperidone disrupted lipid raft domains in the plasma membrane of PBMCs. These results indicated that risperidone alters phospholipid and sphingolipid composition and lipid raft domains in PBMCs of older patients, potentially affecting multiple signaling pathways associated with these membrane domains.
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