Melatonin and neurotrophins NT-3, BDNF, NGF in patients with varying levels of depression severity

Ogłodek, Ewa; Just, M; Szromek, Adam R.; Araszkiewicz, Aleksander

doi:10.1016/j.pharep.2016.04.003

Cited by 63 publications

(41 citation statements)

References 37 publications

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“…It was also pointed out that serum BDNF levels were decreased in SLE patients with depression [28]. However, this does not seem to be specific for SLE, as similar observations were made for depression associated with other disorders, such as Parkinson disease [29], as well as for endogenic depression [30]. In another study, serum BDNF was increased in NPSLE with psychiatric symptoms in comparison with SLE with no neuropsychiatric phenomenology or with neurological symptoms only, and it decreased with symptom improvement [31].…”

Section: Discussionmentioning

confidence: 97%

Immune Cell Neurotrophin Production Is Associated with Subcortical Brain Atrophy in Neuropsychiatric Systemic Lupus Erythematosus Patients

Kalinowska-Łyszczarz

Pawlak

Wyciszkiewicz

et al. 2017

Neuroimmunomodulation

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Objective: Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) remains poorly understood. Damage within the CNS is driven by the autoimmune response; however, immunopathophysiology of neuropsychiatric (NP) SLE is multifactorial. Immune cell neurotrophin production could be neuroprotective against autoimmunity-driven CNS damage, as has been shown in multiple sclerosis. The aim of this study was to establish whether immune cell neurotrophin production is associated with damage severity in NPSLE. Methods: Selected neurotrophins (BDNF, NGF, NT-3, and NT-4/5) were measured with ELISA within peripheral blood mononuclear cells (PBMCs) isolated from 38 NPSLE patients matched with 39 healthy controls. Subcortical and cortical structure volumes were segmented with the Freesurfer 5.3 pipeline on T1-weighted isotropic images acquired on a 1.5-T MRI scanner. Results: BDNF and NGF levels in PBMCs were reduced in NPSLE compared to the healthy population. The PBMC BDNF level was associated with reduced thalamus, caudate, and putamen volumes. The NGF level correlated with lateral ventricles enlargement and thalamic volume loss. Conclusions: In NPSLE, immune cell BDNF and NGF levels are linked with subcortical atrophy. Higher BDNF levels are associated with higher midsagittal atrophy, which may reflect compensatory mechanisms, upregulating BDNF when neuroprotection is needed. These data require further confirmation.

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Section: Discussionmentioning

confidence: 97%

Immune Cell Neurotrophin Production Is Associated with Subcortical Brain Atrophy in Neuropsychiatric Systemic Lupus Erythematosus Patients

Kalinowska-Łyszczarz

Pawlak

Wyciszkiewicz

et al. 2017

Neuroimmunomodulation

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“…In the present study, the patients had increased levels of NGFs and neurotropin-3 (NT3) as compared to CBD and, notably, NGFs were not released from the simulated PBMCs. Low levels of NGFs have been implicated in the pathogenesis of depression and observed in patients with depressive disorders [37,38]. -NGF and NT3 are the NGFs that increase viability, growth and development of neurons and may supress inflammation [39].…”

Section: Discussionmentioning

confidence: 99%

Depression, GABA and age correlate with the plasma levels of inflammatory markers

Bhandage

Cunningham

Jin

et al. 2019

Preprint

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Immunomodulation is increasingly being recognised as a part of mental diseases. Here, we examined if levels of immunological protein markers altered with depression, age or by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).Analysis of plasma samples from patients with major depressive episode and control blood donors (CBD) revealed expression of 67 inflammatory markers. Thirteen of these markers had augmented levels in patients as compared to CBD. and 21 markers correlated with age of the patients, whereas 10 markers correlated with the age of CBD. Interestingly, CST5 and CDCP1 showed the strongest correlation with age in the patients and in the CBD, respectively. IL-18 was the only marker that correlated with the MADRS-S scores of the patients. Neuronal growth factors (NGFs) were significantly enhanced in plasma from the patients and so was the average plasma GABA concentration. GABA modulated release of seven cytokines in CD3 + stimulated peripheral blood mononuclear cells (PBMC) from the patients. The study reveals significant changes in plasma composition of small molecules during depression and identifies potential peripheral biomarkers of the disease.

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“…Melatonin is involved in many biological processes, including sleep-wake timing and blood pressure regulation, mainly through activation of the melatonin receptors MT1 and MT2, which are expressed in many tissues and cells [36,40] . Melatonin is also closely associated with depression as its levels are dramatically decreased in depression patients and is considered to be a significant marker of depression [15][16][17][18][19] . In addition, a melatonin analog, agomelatine, has been approved for major depression treatment [41] .…”

Section: Discussionmentioning

confidence: 99%

“…Clinically, 90% of individuals with major depression suffer from insomnia with an abnormal melatonin pathway function [11][12][13][14] . Many studies have demonstrated that melatonin decreases with a decreased or phase-shifted peak at night are found in patients with depressive disorders [15][16][17][18][19] . The biosynthetic pathway of pineal melatonin has been thoroughly studied and is controlled by the circadian system [9,10] .…”

Section: Introductionmentioning

confidence: 99%

Dendritic cell nuclear protein-1 regulates melatonin biosynthesis by binding to BMAL1 and inhibiting the transcription of N-acetyltransferase in C6 cells

Chen

et al. 2017

Acta Pharmacol Sin

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Dendritic cell nuclear protein-1 (DCNP1) is a protein associated with major depression. In the brains of depression patients, DCNP1 is up-regulated. However, how DCNP1 participates in the pathogenesis of major depression remains unknown. In this study, we first transfected HEK293 cells with EGFP-DCNP1 and demonstrated that the full-length DCNP1 protein was localized in the nucleus, and RRK (the residues 117-119) composed its nuclear localization signal (NLS). An RRK-deletion form of DCNP1 (DCNP1) and truncated form (DCNP1), each lacking the RRK residues, did not show the specific nuclear localization like full-length DCNP1 in the cells. A rat glioma cell line C6 can synthesize melatonin, a hormone that plays important roles in both sleep and depression. We then revealed that transfection of C6 cells with full-length DCNP1 but not DCNP1 or DCNP1 significantly decreased the levels of melatonin. Furthermore, overexpression of full-length DCNP1, but not DCNP1 or DCNP1, in C6 cells significantly decreased both the mRNA and protein levels of N-acetyltransferase (NAT), a key enzyme in melatonin synthesis. Full-length DCNP1 but not DCNP1 or DCNP1 was detected to interact with the Nat promoter and inhibited its activity through its E-box motif. Furthermore, full-length DCNP1 but not the mutants interacted with and repressed the transcriptional activity of BMAL1, a transcription factor that transactivates Nat through the E-box motif. In conclusion, we have shown that RRK (the residues 117-119) are the NLS responsible for DCNP1 nuclear localization. Nuclear DCNP1 represses NAT expression and melatonin biosynthesis by interacting with BMAL1 and repressing its transcriptional activity. Our study reveals a connection between the major depression candidate protein DCNP1, circadian system and melatonin biosynthesis, which may contribute to the pathogenesis of depression.

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Melatonin and neurotrophins NT-3, BDNF, NGF in patients with varying levels of depression severity

Abstract: Melatonin may be a significant marker of depression severity. Melatonin and NF in depressed patients show neuroprotective effects.

Cited by 63 publications

References 37 publications

Immune Cell Neurotrophin Production Is Associated with Subcortical Brain Atrophy in Neuropsychiatric Systemic Lupus Erythematosus Patients

Immune Cell Neurotrophin Production Is Associated with Subcortical Brain Atrophy in Neuropsychiatric Systemic Lupus Erythematosus Patients

Depression, GABA and age correlate with the plasma levels of inflammatory markers

Dendritic cell nuclear protein-1 regulates melatonin biosynthesis by binding to BMAL1 and inhibiting the transcription of N-acetyltransferase in C6 cells

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