Does retinoic acid reverse cell cycle dysregulation in Alzheimer’s disease lymphocytes?

Ashok, Aparna; Naaz, Safoora; Kota, Lakshmi Narayanan; Sen, Somdatta; Purushottam, Meera; Faruq, Mohammed; Kumari, Renu; Yadav, Vinod Kumar; Kannan, R.; Jain, Sanjeev; Panicker, Mitradas M.; Viswanath, Biju

doi:10.1016/j.ajp.2018.08.010

Cited by 9 publications

(9 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given that there are overlaps in cellular mechanisms related to severe mental illnesses, we wanted to see if LCLs derived from OCD patients display abnormal cellular phenotype. Disturbances in cell cycle, as we report here in OCD, have earlier also been reported for depression (Vaidya et al 2007), schizophrenia (Wang et al 2010, Ashok et al, 2019) and bipolar disorder (Paul et al, 2020). Collectively, this suggests that cell cycle dysregulation is a common molecular phenotype across clinically diverse psychiatric disorders.…”

Section: Discussionsupporting

confidence: 87%

“…A previous study showed that the basal prolifera2on of lymphocytes in pa2ents with major depression was significantly higher than in healthy controls, which was reduced by fluoxe2ne in a dose-dependent manner (Fazzino, Montes, Urbina, Carreira, & Lima, 2008). Similar changes in cell cycle have also been demonstrated in lymphoblastoid cell lines (LCLs) derived from pa2ents with other neuropsychiatric disorders like Alzheimer's disease (Ashok et al, 2019) and bipolar disorder (Paul et al, 2019). Another SRI, paroxe2ne, has been shown to cause growth inhibi2on of LCLs of healthy individuals (Morag et al, 2011).…”

Section: Introduconmentioning

confidence: 73%

“…SRIs act through serotonin and dopamine transporters (Lima & Urbina, 2002; Sanders-bush, Hazelwood, 2003), and influence serotonin receptors (Gladkevich, Kauffman, & Korf, 2004); both of which are expressed on lymphocytes. Our lab, and others, have used lymphoblastoid cell lines (LCLs) (derived from lymphocytes) to study cell cycle regulation and cell proliferation, and the effect of SRI response in neuropsychiatric disorders (Breitfeld et al, 2016; Breitfeld, Scholl, Steffens, Laje, & Stingl, 2017; Ashok et al, 2019; Paul et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Abnormal indices of cell cycle regulation have been reported in several psychiatric disorders. Though reports specific to OCD are scant, genomic findings have highlighted partly common underlying biology in psychiatric disorders (Vaidya et al 2007; Wang et al 2010; Ashok et al, 2019; Paul et al, 2020). Therefore, we examined the cell cycle in lymphocytes of patients with OCD and compared them with those of healthy controls.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cell cycle abnormality is a cellular phenotype in OCD

Manjappa

Naaz

Nadella

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Cell cycle abnormalities have been implicated in the pathology of neuropsychiatric disorders. Anti-obsessional agents like the serotonin reuptake inhibitor (SRI), fluoxetine, are known to cause cell cycle arrest. This study aimed at exploring cell cycle abnormalities in obsessive compulsive disorder (OCD) and the effect of in vitro Fluoxetine on lymphoblastoid cell lines (LCLs) derived from OCD patients and healthy controls. The patients had also been systematically characterized for SRI treatment response. LCLs were treated with 10&#956M of Fluoxetine for 24 hours and the percentage of cells in each phase of the cell cycle was determined by flow cytometry, after propidium iodide staining, and analysed using the software FlowJo. We observed a lower proportion of cells in the G2/M phase in OCD cases than controls. Among cases, clinical non-responders to SRI treatment had a lower proportion of cells in G2/M phase than the clinical responders. This suggests that there is a reduction of very specific cell cycle phase in OCD; and this difference is more pronounced in clinical non-responders. Although in-vitro fluoxetine treatment reduced the proportion of cells in G2/M phase overall , this was not specific to any group. The findings suggest that cell cycle G2/M phase dysregulation could be peripheral cellular phenotype for OCD, and a marker for SRI non-response in the clinic.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Introduconmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cell cycle abnormality is a cellular phenotype in OCD

Manjappa

Naaz

Nadella

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Lymphoblastoid cell lines were generated using Epstein Barr Virus from peripheral blood mononuclear cells as previously described [10].The cells were grown in RPMI-1640 (Himedia) medium containing 15% heat-inactivated fetal bovine serum (Gibco), 1%…”

Section: Lcl Generation and Characterizationmentioning

confidence: 99%

Studying cellular functions in bipolar disorder: Are there specific predictors of lithium response?

Paul

Iyer

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

BackgroundLithium is the first-line mood stabilizer for the treatment of bipolar disorder (BD). In order to interrogate cellular phenotypes related to disease and lithium treatment response, this study used neural precursor cells (NPCs) and lymphoblastoid cell lines (LCLs) from BD patients who are well characterized for clinical lithium response. MethodsBD patients diagnosed according to the DSM-IV criteria; were recruited from the outpatient services of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Clinical lithium response was assessed using the "Alda scale" and "NIMH Retrospective Life chart method". The controls were ethnically matched healthy subjects with no family history of neuropsychiatric illness. NPCs from two BD patients from the same family who clearly differed in their clinical response to lithium were chosen, and compared with healthy population controls. Whole transcriptome sequencing (RNA-Seq) and analysis were performed, with and without in vitro lithium (1mM for 7 days).In addition, mitochondrial membrane potential (MMP), cell viability and cell proliferation parameters were examined. Experiments were also performed in 25 LCLs from BD patients (16 lithium responders and 9 lithium non-responders), and 12 healthy control LCLs, to evaluate them in a system amenable to clinical translation. Results RNA-Sequencing and analysis did not reveal differences inNPCs on in vitro lithium treatment. MMP was lower in BD, both in NPCs and LCLs; reversal with in vitro lithium happened only in LCLs and was unrelated to lithium response. Cell proliferation was higher in BD compared to controls, and there was no change on lithium addition. Cell viability assays indicated greater cell death in BD; which could only be rescued in LCLs of clinical Mitradas M. Panicker (Retd.) Faculty of Neurobiology, NCBS, for providing critical inputs during various parts of the project. We are grateful towards Dr Manjunath, Assistant Professor of Neurovirology, NIMHANS and Phillippo, PhD Scholar, NIMHANS for their constructive criticism and valuable suggestions related to FACS experiment and alsoallowing us to access the Flowcytometry facility. We would also like to thank Ms.Varalakshmi R. and Mr. Suneela Kumar B. for the technical support. We would like to thank the clinicians and staff at the NIMHANS; as well as the subjects and their families for their co-operation.

show abstract