Sex Differences in Human Lymphoblastoid Cells Sensitivities to Antipsychotic Drugs

Morag, Ayelet; Oved, Keren; Genevieve, David

doi:10.1007/s12031-012-9852-z

Cited by 11 publications

(9 citation statements)

References 19 publications

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“…Support for the TBI male rats faring worse on motor performance after HAL treatment comes from unilateral sensorimotor cortex lesion studies by Feeney and colleagues (1982) and Goldstein and Bullman (2002). These preclinical findings support clinical data that human males are more sensitive to HAL than females (Morag et al, 2013). …”

Section: Discussionsupporting

confidence: 84%

Comparable impediment of cognitive function in female and male rats subsequent to daily administration of haloperidol after traumatic brain injury

Free

Greene

Bondi

et al. 2017

Experimental Neurology

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Antipsychotic drugs, such as haloperidol (HAL), are prescribed in the clinic to manage traumatic brain injury (TBI)-induced agitation. While preclinical studies have consistently shown that once-daily administration of HAL hinders functional recovery after TBI in male rats, its effects in females are unknown. Hence, the objective of this study was to directly compare neurobehavioral and histological outcomes in both sexes to determine whether the reported deleterious effects of HAL extend to females. Anesthetized adult female and male rats received either a controlled cortical impact (CCI) or sham injury and then were randomly assigned to a dosing regimen of HAL (0.5 mg/kg, i.p.) or vehicle (VEH; 1 mL/kg, i.p.) that was initiated 24 hours after injury and continued once daily for 19 consecutive days. Motor function was tested using established beam-balance/walk protocols on post-operative days 1–5 and acquisition of spatial learning was assessed with a well-validated Morris water maze task on days 14–19. Cortical lesion volume was quantified at 21 days. No statistical differences were revealed between the HAL and VEH-treated sham groups and thus they were pooled for each sex. HAL only impaired motor recovery in males (p < 0.05), but significantly diminished spatial learning in both sexes (p < 0.05). Females, regardless of treatment, exhibited smaller cortical lesions vs VEH-treated males (p < 0.05). Taken together, the data show that daily HAL does not prohibit motor recovery in females, but does negatively impact cognition. These task-dependent differential effects of HAL in female vs male rats may have clinical significance as they can direct therapy.

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Section: Discussionsupporting

confidence: 84%

Comparable impediment of cognitive function in female and male rats subsequent to daily administration of haloperidol after traumatic brain injury

Free

Greene

Bondi

et al. 2017

Experimental Neurology

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“…This property has been recently exploited in association studies of gene expression and disease, and with drug response [63]–[67]. In fact, Bolotin and colleagues demonstrate in their study the overall clustering of gene expression patterns of B cells and LCLs by donor [63].…”

Section: Discussionmentioning

confidence: 97%

Gene Expression Profiling of the Response to Interferon Beta in Epstein-Barr-Transformed and Primary B Cells of Patients with Multiple Sclerosis

et al. 2014

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The effects of interferon-beta (IFN-β), one of the key immunotherapies used in multiple sclerosis (MS), on peripheral blood leukocytes and T cells have been extensively studied. B cells are a less abundant leukocyte type, and accordingly less is known about the B cell-specific response to IFN-β. To identify gene expression changes and pathways induced by IFN-β in B cells, we studied the in vitro response of human Epstein Barr-transformed B cells (lymphoblast cell lines-LCLs), and validated our results in primary B cells. LCLs were derived from an MS patient repository. Whole genome expression analysis identified 115 genes that were more than two-fold differentially up-regulated following IFN-β exposure, with over 50 previously unrecognized as IFN-β response genes. Pathways analysis demonstrated that IFN-β affected LCLs in a similar manner to other cell types by activating known IFN-β canonical pathways. Additionally, IFN-β increased the expression of innate immune response genes, while down-regulating many B cell receptor pathway genes and genes involved in adaptive immune responses. Novel response genes identified herein, NEXN, DDX60L, IGFBP4, and HAPLN3, B cell receptor pathway genes, CD79B and SYK, and lymphocyte activation genes, LAG3 and IL27RA, were validated as IFN-β response genes in primary B cells. In this study new IFN-β response genes were identified in B cells, with possible implications to B cell-specific functions. The study's results emphasize the applicability of LCLs for studies of human B cell drug response. The usage of LCLs from patient-based repositories may facilitate future studies of drug response in MS and other immune-mediated disorders with a B cell component.

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“…Age health status and ethnicity were self-reported by the donors. All cell lines were prepared with EBV generated from the same source of B-95-8 marmoset cell line as described (Morag et al, 2010(Morag et al, , 2013. LCLs were cultured in an RPMI 1640 medium (Sigma-Aldrich) supplemented with 10% foetal bovine serum (Gibco, Grand Island/NY, USA), 4 mM L-glutamine, 100 U/ml penicillin and 100 mg/ml streptomycin (all from Sigma-Aldrich).…”

Section: Lymphoblastoid Cell Linesmentioning

confidence: 99%

“…Human LCLs are emerging as a novel tool for predicting drug responses, adverse drug reactions and for addressing interindividual variability in drug responses (Lock et al, 2012;Morag et al, 2010Morag et al, , 2013. LCLs are generated from peripheral blood lymphocytes by Epstein-Barr virus (EBV) transformation.…”

Section: Introductionmentioning

confidence: 99%

Characterization of human lymphoblastoid cell lines as a novel in vitro test system to predict the immunotoxicity of xenobiotics

et al. 2015

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Sex Differences in Human Lymphoblastoid Cells Sensitivities to Antipsychotic Drugs

Cited by 11 publications

References 19 publications

Comparable impediment of cognitive function in female and male rats subsequent to daily administration of haloperidol after traumatic brain injury

Comparable impediment of cognitive function in female and male rats subsequent to daily administration of haloperidol after traumatic brain injury

Gene Expression Profiling of the Response to Interferon Beta in Epstein-Barr-Transformed and Primary B Cells of Patients with Multiple Sclerosis

Characterization of human lymphoblastoid cell lines as a novel in vitro test system to predict the immunotoxicity of xenobiotics

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