Altered response to mirtazapine on gene expression profile of lymphocytes from Alzheimer's patients

Palotás, András; Puskás, László G.; Kitajka, Klára; Palotás, Miklós; Molnár, J.; Pákáski, Magdolna; Janka, Zoltán; Penke, Botond; Kálmán, János

doi:10.1016/j.ejphar.2004.06.059

Cited by 11 publications

(7 citation statements)

References 36 publications

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“…However, mild/moderate AD dementia cases had reduced numbers of T cells compared to nondemented controls, suggesting that adaptive immune responses may be dysfunctional during the early stages of AD dementia and may contribute to the cognitive decline observed in these individuals. This work complements a number of prior studies which have also demonstrated immune responses in AD, both in the CNS [2,7,12,32] and also from peripheral lymphocytes [27,46,51]. However as we have focused on the dementia component of AD, rather than the pathology, we highlight that this immune response may be directly involved in cognitive decline.…”

Section: Discussionsupporting

confidence: 52%

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Inflammatory changes parallel the early stages of Alzheimer disease

Parachikova

Agadjanyan

Cribbs

et al. 2007

Neurobiology of Aging

182

118

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Alzheimer disease (AD) is the most prominent cause of dementia in the elderly. To determine changes in the AD brain that may mediate the transition into dementia, the gene expression of approximately 10,000 full-length genes was compared in mild/moderate dementia cases to non-demented controls that exhibited high AD pathology. Including this latter group distinguishes this work from previous studies in that it allows analysis of early cognitive loss. Compared to non-demented high-pathology controls, the hippocampus of AD cases with mild/moderate dementia had increased gene expression of the inflammatory molecule major histocompatibility complex (MHC) II, as assessed with microarray analysis. MHC II protein levels were also increased and inversely correlated with cognitive ability. Interestingly, the mild/moderate AD dementia cases also exhibited decreased number of T cells in the hippocampus and the cortex compared to controls. In conclusion, transition into AD dementia correlates with increased MHC II + microglia-mediated immunity and is paradoxically paralleled by a decrease in T cell number, suggesting immune dysfunction.

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Section: Discussionsupporting

confidence: 52%

“…RNA was isolated from the frozen hippocampus and pre-frontal cortex (Brodmann's area 46) by the guanidium thiocyanate method [11] with TRIzol Reagent (LifeTechologies). After RNA isolation, proteins were extracted from the phenol phase following the manufacturer's recommendations (LifeTechologies).…”

Section: Tissue Processingmentioning

confidence: 99%

Inflammatory changes parallel the early stages of Alzheimer disease

Parachikova

Agadjanyan

Cribbs

et al. 2007

Neurobiology of Aging

182

118

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“…Another mechanism of action could be mediated through the upregulation of 5HT transporter by cytokines, such as interleukine (IL)-1h, a-tumor necrosis factor and g-interferon, although IL-4 induces a dose-dependent reduction of this transporter in immortalized B lymphocytes [44]. A recent report, using cDNA microarray representing 3200 distinct human genes, indicates that mirtazapine differentially modifies gene expression in lymphocytes of controls and Alzheimer's patients [45]. At this point we wonder what could be the consequence of 5HT transporter reduction in major depression and the significance of its increase mediated by mirtazapine.…”

Section: Discussionmentioning

confidence: 97%

Effect of mirtazapine treatment on serotonin transporter in blood peripheral lymphocytes of major depression patients

Peña

Baccichet

Urbina

et al. 2005

International Immunopharmacology

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“…Surprisingly, to date, most studies investigating gene expression changes to antidepressant treatment have been performed in patients with Alzheimer's disease, 18, 19, 20 whereas most studies of antidepressant response in depression have been carried out in rodent models. There is limited, although promising, work probing gene expression changes associated with antidepressant response in patients with MDD.…”

Section: Introductionmentioning

confidence: 99%

Gene expression biomarkers of response to citalopram treatment in major depressive disorder

Mamdani

et al. 2011

Transl Psychiatry

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There is significant variability in antidepressant treatment outcome, with ∼30–40% of patients with major depressive disorder (MDD) not presenting with adequate response even following several trials. To identify potential biomarkers of response, we investigated peripheral gene expression patterns of response to antidepressant treatment in MDD. We did this using Affymetrix HG-U133 Plus2 microarrays in blood samples, from untreated individuals with MDD (N=63) ascertained at a community outpatient clinic, pre and post 8-week treatment with citalopram, and used a regression model to assess the impact of gene expression differences on antidepressant response. We carried out technical validation of significant probesets by quantitative reverse transcriptase PCR and conducted central nervous system follow-up of the most significant result in post-mortem brain samples from 15 subjects who died during a current MDD episode and 11 sudden-death controls. A total of 32 probesets were differentially expressed according to response to citalopram treatment following false discovery rate correction. Interferon regulatory factor 7 (IRF7) was the most significant differentially expressed gene and its expression was upregulated by citalopram treatment in individuals who responded to treatment. We found these results to be concordant with our observation of decreased expression of IRF7 in the prefrontal cortex of MDDs with negative toxicological evidence for antidepressant treatment at the time of death. These findings point to IRF7 as a gene of interest in studies investigating genomic factors associated with antidepressant response.

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Altered response to mirtazapine on gene expression profile of lymphocytes from Alzheimer's patients

Cited by 11 publications

References 36 publications

Inflammatory changes parallel the early stages of Alzheimer disease

Inflammatory changes parallel the early stages of Alzheimer disease

Effect of mirtazapine treatment on serotonin transporter in blood peripheral lymphocytes of major depression patients

Gene expression biomarkers of response to citalopram treatment in major depressive disorder

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