Sage Journals: Discover world-class research

Abstract

Background:

Inflammation could be a risk factor for the development of depression and change the outcome of this common chronic-recurrent mental disorder.

Aims:

This study aimed to investigate if bone marrow mononuclear cell (BMMC) transplantation is effective in restoring sucrose preference in rats subjected to chronic stress (CS), if it has an anti-inflammatory effect and is able to restore damaged DNA.

Methods:

The effect of BMMC transplantation was studied in a controlled protocol (compared with a control group and a selective serotonin reuptake inhibitor escitalopram group) involving sucrose preference in CS in rats. Measurements were taken of the amygdala, hippocampus, frontal cortex, and other brain areas, the spleen and blood pro-inflammatory cytokines, namely interleukin-1β, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma, as well as anti-inflammatory cytokine interleukin-10. Finally, 8-hydroxy-2’-deoxyguanosine (a DNA damage marker) was determined.

Results:

BMMC transplantation was as effective as escitalopram in restoring sucrose preference. It also had an anti-inflammatory effect and slightly improved damaged DNA after one week.

Conclusions:

These findings suggest administration of BMMC in rats subjected to CS restores sucrose preference, resolves inflammation in both the peripheral and central nervous system, as well as diminishes DNA damage. This effect was similar to that of escitalopram, which is effective in the treatment of depressive patients.

Keywords

Depression bone marrow mononuclear cells escitalopram chronic stress

Get full access to this article

View all access options for this article.

References

Baptista

PPA

Saur

Bagatini

et al . (2015) Antidepressant effects of ketamine are not related to 18F-FDG metabolism or tyrosine hydroxylase immunoreactivity in the ventral tegmental area of wistar rats. Neurochem Res 40: 1153–1164.

Black

Bot

Scheffer

et al . (2015) Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology 51: 164–175.

Borlongan

(2011) Bone marrow stem cell mobilization in stroke: A ‘bonehead’; may be good after all! Leukemia 25: 1674–1686.

Butterfield

Drake

Chava

et al . (2001) Evidence of oxidative damage in Alzheimer’ s disease brain: Central role for amyloid β-peptide. Trends Mol Med 7: 548–554.

Costa-ferro

ZSM

Souza

BSF

Leal

MMT

et al . (2012) Neurobiology of disease transplantation of bone marrow mononuclear cells decreases seizure incidence, mitigates neuronal loss and modulates pro-inflammatory cytokine production in epileptic rats. Neurobiol Dis 46: 302–313.

Costa-Ferro

ZSM

Vitola

Pedroso

et al . (2010) Prevention of seizures and reorganization of hippocampal functions by transplantation of bone marrow cells in the acute phase of experimental epilepsy. Seizure 19: 84–92.

de Freitas Souza

Nascimento

de Oliveira

et al . (2012) Transplantation of bone marrow cells decreases tumor necrosis factor-α production and blood-brain barrier permeability and improves survival in a mouse model of acetaminophen-induced acute liver disease. Cytotherapy 14: 1011–1021.

Eyre

Baune

(2012) Neuroplastic changes in depression: A role for the immune system. Psychoneuroendocrinology 37: 1397–1416.

Forlenza

Miller

(2006) Increased serum levels of 8-hydroxy-2′-deoxyguanosine in clinical depression. Psychosom Med 68: 1–7.

10.

Janakiraman

Manivasagam

Thenmozhi

et al . (2016) Influences of chronic mild stress exposure on motor, non-motor impairments and neurochemical variables in specific brain areas of MPTP/probenecid induced neurotoxicity in mice. PLoS One 11: e0146671.

11.

Jayatissa

Bisgaard

Tingström

et al . (2006) Hippocampal cytogenesis correlates to escitalopram-mediated recovery in a chronic mild stress rat model of depression. Neuropsychopharmacology 31: 2395–2404.

12.

Katon

Fan

M-y

Unützer

et al . (2008) Depression and diabetes: A potentially lethal combination. J Gen Intern Med 23: 1571–1575.

13.

Köhler

Freitas

Maes

et al . (2017) Peripheral cytokine and chemokine alterations in depression: A meta-analysis of 82 studies. Acta Psychiatrica Scandinavica 135: 373–387.

14.

Leal

MMT

Costa-Ferro

Souza

et al . (2014) Early transplantation of bone marrow mononuclear cells promotes neuroprotection and modulation of inflammation after status epilepticus in mice by paracrine mechanisms. Neurochem Res 39: 259–268.

15.

Liu

Wang

Shigenaga

et al . (1996) Immobilization stress causes oxidative damage to lipid, protein, and DNA in the brain of rats. FASEB J 10: 1532–1538.

16.

Maluach

Misquitta

Prevot

et al . (2017) Increased neuronal DNA/RNA oxidation in the frontal cortex of mice subjected to unpredictable chronic mild stress. Chronic Stress. doi: 10.1177/2470547017724744.

17.

Martin

Teismann

(2009) Glutathione—a review on its role and significance in Parkinson’s disease. FASEB J 23: 3263–3272.

18.

Miller

Raison

(2016) The role of inflammation in depression: From evolutionary imperative to modern treatment target. Nat Rev Immunol 16: 22–34.

19.

Moylan

Maes

Wray

et al . (2012) The neuroprogressive nature of major depressive disorder: Pathways to disease evolution and resistance, and therapeutic implications. Mol Psychiatry 18: 595–606.

20.

Nicholson

Kuper

Hemingway

(2006) Depression as an aetiologic and prognostic factor in coronary heart disease: A meta-analysis of 6362 events among 146 538 participants in 54 observational studies. Eur Heart J 27: 2763–2774.

21.

Pierce

Begun

Westendorf

et al . (2019) Defining osteoblast and adipocyte lineages in the bone marrow. Bone 118: 2–7.

22.

Rosenblat

Cha

Mansur

et al . (2014) Inflamed moods: A review of the interactions between inflammation and mood disorders. Prog Neuropsychopharmacol Biol Psychiatry 53: 23–34.

23.

Russo

Nestler

(2013) The brain reward circuitry in mood disorders. Nat Rev Neurosci 14: 609–625.

24.

Setiawan

Attwells

Wilson

et al . (2018) Articles association of translocator protein total distribution volume with duration of untreated major depressive disorder: A cross-sectional study. Lancet Psychiatry 5: 339–347.

25.

Slavich

Irwin

(2014) From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. Psychol Bull 140: 774–815.

26.

Venturin

Greggio

Marinowic

et al . (2011) Bone marrow mononuclear cells reduce seizure frequency and improve cognitive outcome in chronic epileptic rats. Life Sci 89: 229–234.

27.

Willner

(2005) Chronic mild stress (CMS) revisited: Consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology 52: 90–110.

28.

Woelfer

Kasties

Walter

(2019) The role of depressive subtypes within the neuroinflammation hypothesis of major depressive disorder. Neuroscience 403: 93–110.

29.

World Health Organization (2017) Depression and Other Common Mental Disorders: Global Health Estimates. Geneva: World Health Organization, p.24.

30.

Yao

Leonard

Reddy

(2006) Altered glutathione redox state in schizophrenia. Dis Markers 22: 83–93.

31.

Zanirati

Azevedo

Marinowic

et al . (2015) Transplantation of bone marrow mononuclear cells modulates hippocampal expression of growth factors in chronically epileptic animals. CNS Neurosci Ther 21: 463–471.

32.

Zhou

Liu

et al . (2018) Quantitative proteomic analysis reveals synaptic dysfunction in the amygdala of rats susceptible to chronic mild stress. Neuroscience 376: 24–39.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.34 MB

The antidepressant effect of bone marrow mononuclear cell transplantation in chronic stress