The Antipsychotic Risperidone Alters Dihydroceramide and Ceramide Composition and Plasma Membrane Function in Leukocytes In Vitro and In Vivo

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.

Inflammatory Thyroid Changes Following Serotonin Receptor Blocking in Experimental Rats

“…However, both drugs have a significant beneficial effect in treating mental disorders including depression. 25 Therefore, it can be said that although the subjects who receive the following results do not require regular or frequent monitoring of thyroid hormones in long-term use and the use of the drug in higher concentration there must be a check as long-term use is associated with hyperthyroidism. However, the surrounding milieu greatly impact the response to the therapy, therefore, when endogenously applied agents used their impact on thyroid is greatly under control of the cellular response due to proinflammatory/anti-inflammatory cytokine released 26,27 and greatly impact by localized tissue oxygenation.…”

Rottlerin Stimulates Exosome/Microvesicle Release Via the Increase of Ceramide Levels Mediated by Ampk in an In Vitro Model of Intracellular Lipid Accumulation

“…To elucidate the mechanism responsible for the effects of rottlerin, we characterized several pathways. Based on previous studies by Kosaka et al showing that rottlerin increased ceramide concentrations after long treatments [ 17 ], and our results on the action of other drugs and compounds on intracellular lipid trafficking [ 10 , 40 ], we first focused on sphingolipid metabolism. We showed that rottlerin treatment increased ceramide content in C6 cells, together with the degradation of hexosylceramides.…”

Plasma Lysophosphatidylcholine and Lysophosphatidylethanolamine Levels Were Associated With the Therapeutic Response to Olanzapine in Female Antipsychotics-naïve First-episode Patients With Schizophrenia

“…Lysoglycerophospholipid plays a fundamental role in the neuronal mechanisms underlying the pathophysiological feature of several psychiatric disorders. Moreover, atypical antipsychotic medication has been shown to alter the levels of LPE and LPC in mental disorders ( Ask et al, 2016 ; Cao et al, 2019 ; Leppik et al, 2020 ; Canfrán-Duque et al, 2021 ). In line with our findings, Cao et al found that after 8-wk treatment with antipsychotics, serum amino acids and LPC levels were increased in first-episode (FEP) patients with schizophrenia ( n = 122) ( Cao et al, 2019 ).…”