Abstract
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.
Highlights
Antipsychotic drugs are widely used to manage psychiatric disorders
This study evaluates the effects of risperidone treatment on phospholipid and sphingolipid composition and lipid raft function in peripheral blood mononuclear cells (PBMCs) of older patients with dementia compared with patients not receiving antipsychotic
This study demonstrates that a 3-month risperidone treatment in older patients alters the phospholipid and sphingolipid composition of circulating PBMCs and disrupts detergent-resistant or lipid raft domains in the plasma membrane
Summary
Antipsychotic drugs are widely used to manage psychiatric disorders. These drugs are classified into typical or first-generation antipsychotics (FGAs), atypical or secondgeneration antipsychotics (SGAs), and third-generation antipsychotics. FGAs and SGAs inhibit cholesterol biosynthesis in vitro by decreasing the activity of enzymes involved in this pathway, resulting in the accumulation of different sterol intermediates [7,9,10,11] This alteration in sterol composition affects lipid raft formation and hormone signaling, as demonstrated for insulin and somatostatin in cells treated with the FGA haloperidol [9,10]. The results showed that risperidone decreased the levels of dihydroceramides, very-longchain ceramides, and lysophosphatidylcholines in treated patients This drug disrupted lipid raft domains in the plasma membranes of PBMCs. this drug disrupted lipid raft domains in the plasma membranes of PBMCs These results indicate that risperidone alters the phospholipid and sphingolipid composition and impairs lipid rafts in PBMCs of older persons, and these changes can potentially affect multiple signaling pathways
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