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Lipid rafts are specialized membrane microdomains enriched in cholesterol and sphingolipids and are important in the organization of receptor-protein complexes and the regulation of signaling.
Given the emerging significance of lipids with respect to receptor structure and activation, we investigated the role of lipid rafts and membrane cholesterol on D2 dopamine receptor (DAR) signaling. As the D2 DAR is the molecular target for all antipsychotic drugs, more information about its signaling may help refine therapeutics for schizophrenia.
D2 DAR constructs were expressed in HEK293T cells. Sucrose density fractionation resolved lipid rafts from other membrane components. Methyl-β-cyclodextrin (MCD) was used to deplete membrane cholesterol and to disrupt lipid rafts.
Detergent solubilization followed by sucrose gradient centrifugation resolved lipid rafts from heavier membrane fractions. The D2 DAR was equally distributed amongst both the lipid raft and heavier membrane fractions. Pretreatment with MCD, however, eliminated both lipid raft markers and the D2 DAR from lipid raft fractions, although the receptor was still found in heavier membrane fractions. We also found that MCD treatment abolished D2 DAR-mediated inhibition of cAMP accumulation. In contrast D1 DAR-stimulated cAMP accumulation was unaffected by MCD treatment.
Our current results show that the D2 DAR is distributed in multiple membrane microdomains, including cholesterol-rich lipid rafts. We found that extraction of cholesterol disrupted lipid rafts and also an eliminated D2 DAR-mediated signaling. Thus, we hypothesize that lipid rafts are critical for D2 DAR signaling to occur.
Schizophrenia is a psychotic disorder that is stereotypically stigmatised as untreatable and associated with violence. Several authorities have suggested that changing the name, for example to psychosis, would reduce such stigmatisation. We aimed to compare attitudes to schizophrenia and psychosis on Twitter to see if psychosis was associated with less negative attitudes. Tweets containing the terms ‘schizophrenia’, ‘schizophrenic’, ‘psychosis’ or ‘psychotic’ were collected on www.twitter.com and were captured with NCapture. On NVivo, tweets were coded into categories based on user type, tweet content, attitude and stigma type by two independent raters. We compared the content and attitudes of tweets referring to schizophrenia/schizophrenic and psychosis/psychotic.
A total of 1120 tweets referring to schizophrenia/schizophrenic and 1080 referring to psychosis/psychotic were identified over two 7-day periods; 424 original tweets for schizophrenia and 416 original tweets for psychosis were included in the analysis. Psychosis was significantly more commonly included in tweets expressing negative attitudes (n=131, 31.5%) than schizophrenia (n=41, 9.7%) (χ² = 237.03, P < 0.0001). Of the personal opinions or dyadic interactions, 125 (53.4%) in the psychosis data set were stigmatising, compared with 33 (24.6%) of those in the schizophrenia set (χ² = 44.65, P < 0.0001).
The terms psychosis/psychotic are associated with a significantly higher number of tweets with negative content than schizophrenia/schizophrenic. Together with other evidence, this suggests that changing the name of schizophrenia to psychosis will not reduce negative attitudes toward the condition.
Declaration of interest
S.L. has received personal fees from Otsuka and Sunovion, and personal and research fees from Janssen.
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