Skip to main content Accessibility help

Markers of HPA-axis activity and nucleic acid damage from oxidation after electroconvulsive stimulations in rats

  • Anders Jorgensen (a1) (a2), Katrine Breitenstein (a2), Otto Kalliokoski (a3), Allan Weimann (a4) (a5), Trine Henriksen (a4) (a5), Henrik Enghusen Poulsen (a4) (a5), Martin Balslev Jorgensen (a1) (a2) and Gitta Wörtwein (a2)...



Oxidative stress has been suggested to increase after electroconvulsive therapy (ECT), a treatment which continues to be the most effective for severe depression. Oxidative stress could potentially be mechanistically involved in both the therapeutic effects and side effects of ECT.


We measured sensitive markers of systemic and central nervous system (CNS) oxidative stress on DNA and RNA (urinary 8-oxodG/8-oxoGuo, cerebrospinal fluid 8-oxoGuo, and brain oxoguanine glycosylase mRNA expression) in male rats subjected to electroconvulsive stimulations (ECS), an animal model of ECT. Due to the previous observations that link hypothalamic–pituitary–adrenal (HPA)-axis activity and age to DNA/RNA damage from oxidation, groups of young and middle-aged male animals were included, and markers of HPA-axis activity were measured.


ECS induced weight loss, increased corticosterone (only in middle-aged animals), and decreased cerebral glucocorticoid receptor mRNA expression, while largely leaving the markers of systemic and CNS DNA/RNA damage from oxidation unaltered.


These results suggest that ECS is not associated with any lasting effects on oxidative stress on nucleic acids neither in young nor middle-aged rats.


Corresponding author

Author for correspondence: Anders Jorgensen, E-mail:


Hide All

These authors contributed equally.



Hide All
Barichello, T, Bonatto, F, Feier, G, Martins, MR, Moreira, JC, Dal-Pizzol, F, Izquierdo, I and Quevedo, J (2004) No evidence for oxidative damage in the hippocampus after acute and chronic electroshock in rats. Brain Research 1014, 177183.
Barregard, L, Moller, P, Henriksen, T, Mistry, V, Koppen, G, Rossner, P Jr., Sram, RJ, Weimann, A, Poulsen, HE, Nataf, R and Andreoli, R (2013) Human and methodological sources of variability in the measurement of urinary 8-oxo-7, 8-dihydro-2’-deoxyguanosine. Antioxidants & Redox Signaling 18, 23772391.
Bodine, SC and Furlow, JD (2015) Glucocorticoids and skeletal muscle. Advances in Experimental Medicine and Biology 872, 145176.
Bolwig, TG (2011) How does electroconvulsive therapy work? Theories on its mechanism. The Canadian Journal of Psychiatry 56, 1318.
Chen, F, Madsen, TM, Wegener, G and Nyengaard, JR (2009) Repeated electroconvulsive seizures increase the total number of synapses in adult male rat hippocampus. European Neuropsychopharmacology 19, 329338.
Deng, XS, Tuo, J, Poulsen, HE and Loft, S (1998) Prevention of oxidative DNA damage in rats by brussels sprouts. Free Radical Research 28, 323333.
Dessens, FM, van Paassen, J, van Westerloo, DJ, van der Wee, NJ, van Vliet, IM and van Noorden, MS (2016) Electroconvulsive therapy in the intensive care unit for the treatment of catatonia: a case series and review of the literature. General Hospital Psychiatry 38, 3741.
Epel, ES (2009) Psychological and metabolic stress: a recipe for accelerated cellular aging? Hormones(Athens) 8, 722.
Feier, G, Jornada, LK, Barichello, T, Vitali, AM, Bonatto, F, Moreira, JC, Dal-Pizzol, F and Quevedo, J (2006) Long lasting effects of electroconvulsive seizures on brain oxidative parameters. Neurochemical Research 31, 665670.
Flint, MS, Baum, A, Chambers, WH and Jenkins, FJ (2007) Induction of DNA damage, alteration of DNA repair and transcriptional activation by stress hormones. Psychoneuroendocrinology 32, 470479.
Gaffey, AE, Bergeman, CS, Clark, LA and Wirth, MM (2016) Aging and the HPA axis: stress and resilience in older adults. Neuroscience & Biobehavioral Reviews 68, 928945.
Hageman, I, Nielsen, M, Wortwein, G, Diemer, NH and Jorgensen, MB (2008) Electroconvulsive stimulations prevent stress-induced morphological changes in the hippocampus. Stress 11, 282289.
Hageman, I, Nielsen, M, Wortwein, G, Diemer, NH and Jorgensen, MB (2009) Electroconvulsive stimulations normalizes stress-induced changes in the glucocorticoid receptor and behaviour. Behavioural Brain Research 196, 7177.
Henriksen, T, Hillestrom, PR, Poulsen, HE and Weimann, A (2009) Automated method for the direct analysis of 8-oxo-guanosine and 8-oxo-2’-deoxyguanosine in human urine using ultraperformance liquid chromatography and tandem mass spectrometry. Free Radical Biology and Medicine 47, 629635.
Hjaeresen, ML, Hageman, I, Wortwein, G and Jorgensen, MB (2012) Time course and duration of changes in Kv7.2 and Kv11.1 mRNA expression in the hippocampus and piriform cortex following electroconvulsive stimulations. Brain Stimulation 5, 5560.
Joergensen, A, Broedbaek, K, Weimann, A, Semba, RD, Ferrucci, L, Joergensen, MB and Poulsen, HE (2011) Association between urinary excretion of cortisol and markers of oxidatively damaged DNA and RNA in humans. PLoSOne 6, e20795.
Jorgensen, A, Broedbaek, K, Fink-Jensen, A, Knorr, U, Greisen Soendergaard, M, Henriksen, T, Weimann, A, Jepsen, P, Lykkesfeldt, J, Poulsen, HE and Jorgensen, MB (2013a) Increased systemic oxidatively generated DNA and RNA damage in schizophrenia. Psychiatry Research 209, 417423.
Jorgensen, A, Kalliokoski, O, Forsberg, K, Breitenstein, K, Weimann, A, Henriksen, T, Hau, J, Wörtwein, G, Poulsen, HE and Jorgensen, MB (2017) A chronic increase of corticosterone age-dependently reduces systemic DNA damage from oxidation in rats. Free Radical Biology and Medicine 104, 6474.
Jorgensen, A, Krogh, J, Miskowiak, K, Bolwig, TG, Kessing, LV, Fink-Jensen, A, Nordentoft, M, Henriksen, T, Weimann, A, Poulsen, HE and Jorgensen, MB (2013b) Systemic oxidatively generated DNA/RNA damage in clinical depression: associations to symptom severity and response to electroconvulsive therapy. The Journal of Affective Disorders 149, 355362.
Jorgensen, A, Magnusson, P, Hanson, LG, Kirkegaard, T, Benveniste, H, Lee, H, Svarer, C, Mikkelsen, JD, Fink-Jensen, A, Knudsen, GM and Paulson, OB (2016) Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression. Acta Psychiatrica Scandinavica 133, 154164.
Jorgensen, A, Maigaard, K, Wortwein, G, Hageman, I, Henriksen, T, Weimann, A, Møller, P, Loft, S, Hau, J, Poulsen, HE and Jorgensen, MB (2013c) Chronic restraint stress in rats causes sustained increase in urinary corticosterone excretion without affecting cerebral or systemic oxidatively generated DNA/RNA damage. Progress in Neuro-Psychopharmacology & Biological Psychiatry 40, 3037.
Jornada, LK, Feier, G, Barichello, T, Vitali, AM, Reinke, A, Gavioli, EC, Dal-Pizzol, F and Quevedo, J (2007) Effects of maintenance electroshock on the oxidative damage parameters in the rat brain. Neurochemical Research 32, 389394.
Joshi, SH, Espinoza, RT, Pirnia, T, Shi, J, Wang, Y, Ayers, B, Leaver, A, Woods, RP and Narr, KL (2016) Structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy in major depression. Biological Psychiatry 79, 282292.
Madsen, TM, Treschow, A, Bengzon, J, Bolwig, TG, Lindvall, O and Tingstrom, A (2000) Increased neurogenesis in a model of electroconvulsive therapy. Biological Psychiatry 47, 10431049.
Mahat, MY, Fakrudeen Ali Ahamed, N, Chandrasekaran, S, Rajagopal, S, Narayanan, S and Surendran, N (2012) An improved method of transcutaneous cisterna magna puncture for cerebrospinal fluid sampling in rats. The Journal of Neuroscience Methods 211, 272279.
Moller, P, Lohr, M, Folkmann, JK, Mikkelsen, L and Loft, S (2010) Aging and oxidatively damaged nuclear DNA in animal organs. Free Radical Biology and Medicine 48, 12751285.
Nater, UM, Hoppmann, CA and Scott, SB (2013) Diurnal profiles of salivary cortisol and alpha-amylase change across the adult lifespan: evidence from repeated daily life assessments. Psychoneuroendocrinology 38, 31673171.
Nielsen, RM, Olsen, KS, Lauritsen, AO and Boesen, HC (2014) Electroconvulsive therapy as a treatment for protracted refractory delirium in the intensive care unit -- five cases and a review. Journal of Critical Care 29, 881.e1886.e6.
Osler, M, Rozing, MP, Christensen, GT, Andersen, PK and Jorgensen, MB (2018) Electroconvulsive therapy and risk of dementia in patients with affective disorders: a cohort study. The Lancet Psychiatry 5, 348356.
Poulsen, HE, Nadal, LL, Broedbaek, K, Nielsen, PE and Weimann, A (2014) Detection and interpretation of 8-oxodG and 8-oxoGua in urine, plasma and cerebrospinal fluid. Biochimica et Biophysica Acta 1840, 801808.
Rasmussen, ST, Andersen, JT, Nielsen, TK, Cejvanovic, V, Petersen, KM, Henriksen, T, Weimann, A, Lykkesfeldt, J and Poulsen, HE (2016) Simvastatin and oxidative stress in humans: a randomized, double-blinded, placebo-controlled clinical trial. Redox Biology 9, 3238.
Semkovska, M and McLoughlin, DM (2010) Objective cognitive performance associated with electroconvulsive therapy for depression: a systematic review and meta-analysis. Biological Psychiatry 68, 568577.
Semkovska, M and McLoughlin, DM (2013) Measuring retrograde autobiographical amnesia following electroconvulsive therapy: historical perspective and current issues. The Journal of ECT 29, 127133.
Suijk, DLS, Dols, A, van Exel, E, Stek, ML, Veltman, E, Bouckaert, F, Sienaert, P and Rhebergen, D (2018) Salivary cortisol as predictor for depression characteristics and remission in electroconvulsive therapy in older persons. The World Journal of Biological Psychiatry Feb 21, 18.
UK_ECT_Review_Group (2003) Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 361, 799808.
Zupan, G, Pilipovic, K, Hrelja, A and Peternel, S (2008) Oxidative stress parameters in different rat brain structures after electroconvulsive shock-induced seizures. Progress in Neuro-Psychopharmacology & Biological Psychiatry 32, 771777.


Markers of HPA-axis activity and nucleic acid damage from oxidation after electroconvulsive stimulations in rats

  • Anders Jorgensen (a1) (a2), Katrine Breitenstein (a2), Otto Kalliokoski (a3), Allan Weimann (a4) (a5), Trine Henriksen (a4) (a5), Henrik Enghusen Poulsen (a4) (a5), Martin Balslev Jorgensen (a1) (a2) and Gitta Wörtwein (a2)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed