Hostname: page-component-78c5997874-4rdpn Total loading time: 0 Render date: 2024-11-04T21:54:09.679Z Has data issue: false hasContentIssue false

Peroxisome proliferator-activated receptor gamma co-activator-1 alpha in depression and the response to electroconvulsive therapy

Published online by Cambridge University Press:  07 September 2018

Karen M. Ryan
Affiliation:
Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland Department of Psychiatry, St. Patrick's University Hospital, Trinity College Dublin, Dublin, Ireland
Ian Patterson
Affiliation:
Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
Declan M. McLoughlin*
Affiliation:
Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland Department of Psychiatry, St. Patrick's University Hospital, Trinity College Dublin, Dublin, Ireland
*
Author for correspondence: Declan M. McLoughlin, E-mail: [email protected]

Abstract

Background

The transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC-1α), termed the ‘master regulator of mitochondrial biogenesis’, has been implicated in stress and resilience to stress-induced depressive-like behaviours in animal models. However, there has been no study conducted to date to examine PGC-1α levels in patients with depression or in response to antidepressant treatment. Our aim was to assess PGC-1α mRNA levels in blood from healthy controls and patients with depression pre-/post-electroconvulsive therapy (ECT), and to examine the relationship between blood PGC-1α mRNA levels and clinical symptoms and outcomes with ECT.

Methods

Whole blood PGC-1α mRNA levels were analysed in samples from 67 patients with a major depressive episode and 70 healthy controls, and in patient samples following a course of ECT using quantitative real-time polymerase chain reaction (qRT-PCR). Exploratory subgroup correlational analyses were carried out to determine the relationship between PGC-1α and mood scores.

Results

PGC-1α levels were lower in patients with depression compared with healthy controls (p = 0.03). This lower level was predominantly accounted for by patients with psychotic unipolar depression (p = 0.004). ECT did not alter PGC-1α levels in the depressed group as a whole, though exploratory analyses revealed a significant increase in PGC-1α in patients with psychotic unipolar depression post-ECT (p = 0.045). We found no relationship between PGC-1α mRNA levels and depression severity or the clinical response to ECT.

Conclusions

PGC-1α may represent a novel therapeutic target for the treatment of depression, and be a common link between various pathophysiological processes implicated in depression.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abe, N, Uchida, S, Otsuki, K, Hobara, T, Yamagata, H, Higuchi, F, Shibata, T and Watanabe, Y (2011) Altered sirtuin deacetylase gene expression in patients with a mood disorder. Journal of Psychiatric Research 45, 11061112.Google Scholar
Agudelo, LZ, Femenia, T, Orhan, F, Porsmyr-Palmertz, M, Goiny, M, Martinez-Redondo, V, Correia, JC, Izadi, M, Bhat, M, Schuppe-Koistinen, I, Pettersson, AT, Ferreira, DMS, Krook, A, Barres, R, Zierath, JR, Erhardt, S, Lindskog, M and Ruas, JL (2014) Skeletal muscle PGC-1alpha1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. Cell 159, 3345.Google Scholar
Aguirre-Rueda, D, Guerra-Ojeda, S, Aldasoro, M, Iradi, A, Obrador, E, Ortega, A, Mauricio, MD, Vila, JM and Valles, SL (2015) Astrocytes protect neurons from Abeta1-42 peptide-induced neurotoxicity increasing TFAM and PGC-1 and decreasing PPAR-gamma and SIRT-1. International Journal of Medical Sciences 12, 4856.Google Scholar
Als, TD, Dahl, HA, Flint, TJ, Wang, AG, Vang, M, Mors, O, Kruse, TA and Ewald, H (2004) Possible evidence for a common risk locus for bipolar affective disorder and schizophrenia on chromosome 4p16 in patients from the Faroe Islands. Molecular Psychiatry 9, 9398.Google Scholar
Arany, Z, Foo, SY, Ma, Y, Ruas, JL, Bommi-Reddy, A, Girnun, G, Cooper, M, Laznik, D, Chinsomboon, J, Rangwala, SM, Baek, KH, Rosenzweig, A and Spiegelman, BM (2008) HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature 451, 10081012.Google Scholar
Beckham, EE and Leber, WR (1985) Hamilton Rating Scale for Depression, ECDEU Version Used in the Treatment of Depression Collaborative Research Program. Homewood: The Dorsey Press.Google Scholar
Berlim, MT, Van den Eynde, F and Daskalakis, ZJ (2013) Efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (rTMS) versus electroconvulsive therapy (ECT) for major depression: a systematic review and meta-analysis of randomized trials. Depression and Anxiety 30, 614623.Google Scholar
Blackwood, DH, He, L, Morris, SW, McLean, A, Whitton, C, Thomson, M, Walker, MT, Woodburn, K, Sharp, CM, Wright, AF, Shibasaki, Y, St Clair, DM, Porteous, DJ and Muir, WJ (1996) A locus for bipolar affective disorder on chromosome 4p. Nature Genetics 12, 427430.Google Scholar
Buler, M, Aatsinki, SM, Skoumal, R, Komka, Z, Toth, M, Kerkela, R, Georgiadi, A, Kersten, S and Hakkol, J (2012) Energy-sensing factors coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) and AMP-activated protein kinase control expression of inflammatory mediators in liver: induction of interleukin 1 receptor antagonist. Journal of Biological Chemistry 287, 18471860.Google Scholar
Burigo, M, Roza, CA, Bassani, C, Fagundes, DA, Rezin, GT, Feier, G, Dal-Pizzol, F, Quevedo, J and Streck, EL (2006) Effect of electroconvulsive shock on mitochondrial respiratory chain in rat brain. Neurochemical Research 31, 13751379.Google Scholar
Carvalho, AF, Kohler, CA, McIntyre, RS, Knochel, C, Brunoni, AR, Thase, ME, Quevedo, J, Fernandes, BS and Berk, M (2015) Peripheral vascular endothelial growth factor as a novel depression biomarker: a meta-analysis. Psychoneuroendocrinology 62, 1826.Google Scholar
Chang, HC and Guarente, L (2013) SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell 153, 14481460.Google Scholar
Chang, CC, Jou, SH, Lin, TT, Lai, TJ and Liu, CS (2015) Mitochondria DNA change and oxidative damage in clinically stable patients with major depressive disorder. PLoS One 10, e0125855.Google Scholar
Christoforou, A, Le Hellard, S, Thomson, PA, Morris, SW, Tenesa, A, Pickard, BS, Wray, NR, Muir, WJ, Blackwood, DH, Porteous, DJ and Evans, KL (2007) Association analysis of the chromosome 4p15-p16 candidate region for bipolar disorder and schizophrenia. Molecular Psychiatry 12, 10111025.Google Scholar
Ciron, C, Lengacher, S, Dusonchet, J, Aebischer, P and Schneider, BL (2012) Sustained expression of PGC-1alpha in the rat nigrostriatal system selectively impairs dopaminergic function. Human Molecular Genetics 21, 18611876.Google Scholar
Clark, J, Reddy, S, Zheng, K, Betensky, RA and Simon, DK (2011) Association of PGC-1alpha polymorphisms with age of onset and risk of Parkinson's disease. BMC Medical Genetics 12, 69.Google Scholar
Clark, J, Silvaggi, JM, Kiselak, T, Zheng, K, Clore, EL, Dai, Y, Bass, CE and Simon, DK (2012) Pgc-1alpha overexpression downregulates Pitx3 and increases susceptibility to MPTP toxicity associated with decreased Bdnf. PLoS One 7, e48925.Google Scholar
Cobb, JA, O'Neill, K, Milner, J, Mahajan, GJ, Lawrence, TJ, May, WL, Miguel-Hidalgo, J, Rajkowska, G and Stockmeier, CA (2016) Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder. Neuroscience 316, 209220.Google Scholar
Coppen, A (1967) The biochemistry of affective disorders. British Journal of Psychiatry 113, 12371264.Google Scholar
Cowell, RM, Blake, KR and Russell, JW (2007) Localization of the transcriptional coactivator PGC-1alpha to GABAergic neurons during maturation of the rat brain. Journal of Comparative Neurology 502, 118.Google Scholar
Dougherty, SE, Bartley, AF, Lucas, EK, Hablitz, JJ, Dobrunz, LE and Cowell, RM (2014) Mice lacking the transcriptional coactivator PGC-1alpha exhibit alterations in inhibitory synaptic transmission in the motor cortex. Neuroscience 271, 137148.Google Scholar
Dowlati, Y, Herrmann, N, Swardfager, W, Liu, H, Sham, L, Reim, EK and Lanctot, KL (2010) A meta-analysis of cytokines in major depression. Biological Psychiatry 67, 446457.Google Scholar
Duman, RS and Vaidya, VA (1998) Molecular and cellular actions of chronic electroconvulsive seizures. Journal of ECT 14, 181193.Google Scholar
Esterbauer, H, Oberkofler, H, Krempler, F and Patsch, W (1999) Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression. Genomics 62, 98102.Google Scholar
Fernandez-Marcos, PJ and Auwerx, J (2011) Regulation of PGC-1alpha, a nodal regulator of mitochondrial biogenesis. The American Journal of Clinical Nutrition 93, 884S890S.Google Scholar
First, M, Spitzer, R, Gibbon, M and Williams, J (1996) Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV). Washington, DC: American Psychiatric Press.Google Scholar
Friedrich, MJ (2017) Depression is the leading cause of disability around the world. JAMA 317, 1517.Google Scholar
Gardner, A and Boles, RG (2011) Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders. Progress in Neuropsychopharmacology and Biological Psychiatry 35, 730743.Google Scholar
Garlanda, C, Dinarello, CA and Mantovani, A (2013) The interleukin-1 family: back to the future. Immunity 39, 10031018.Google Scholar
Geoffroy, PA, Etain, B, Lajnef, M, Zerdazi, EH, Brichant-Petitjean, C, Heilbronner, U, Hou, L, Degenhardt, F, Rietschel, M, McMahon, FJ, Schulze, TG, Jamain, S, Marie-Claire, C and Bellivier, F (2016) Circadian genes and lithium response in bipolar disorders: associations with PPARGC1A (PGC-1alpha) and RORA. Genes, Brain and Behavior 15, 660668.Google Scholar
Glombik, K, Stachowicz, A, Slusarczyk, J, Trojan, E, Budziszewska, B, Suski, M, Kubera, M, Lason, W, Wedzony, K, Olszanecki, R and Basta-Kaim, A (2015) Maternal stress predicts altered biogenesis and the profile of mitochondrial proteins in the frontal cortex and hippocampus of adult offspring rats. Psychoneuroendocrinology 60, 151162.Google Scholar
Guloksuz, S, Arts, B, Walter, S, Drukker, M, Rodriguez, L, Myint, AM, Schwarz, MJ, Ponds, R, van Os, J, Kenis, G and Rutten, BP (2015) The impact of electroconvulsive therapy on the tryptophan-kynurenine metabolic pathway. Brain Behaviour and Immunity 48, 4852.Google Scholar
Harkin, A (2014) Muscling in on depression. New England Journal of Medicine 371, 23332334.Google Scholar
Howren, MB, Lamkin, DM and Suls, J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosomatic Medicine 71, 171186.Google Scholar
Jang, WG, Kim, EJ, Park, KG, Park, YB, Choi, HS, Kim, HJ, Kim, YD, Kim, KS, Lee, KU and Lee, IK (2007) Glucocorticoid receptor mediated repression of human insulin gene expression is regulated by PGC-1alpha. Biochemical and Biophysical Research Communication 352, 716721.Google Scholar
Jarventausta, K, Sorri, A, Kampman, O, Bjorkqvist, M, Tuohimaa, K, Hamalainen, M, Moilanen, E, Leinonen, E, Peltola, J and Lehtimaki, K (2017) Changes in interleukin-6 levels during electroconvulsive therapy may reflect the therapeutic response in major depression. Acta Psychiatrica Scandinavica 135, 8792.Google Scholar
Jeong, J, Park, M, Yoon, JS, Kim, H, Lee, SK, Lee, E, Namkoong, K and Kim, E (2015) Requirement of AMPK activation for neuronal metabolic-enhancing effects of antidepressant paroxetine. Neuroreport 26, 424428.Google Scholar
Jiang, H, Kang, SU, Zhang, S, Karuppagounder, S, Xu, J, Lee, YK, Kang, BG, Lee, Y, Zhang, J, Pletnikova, O, Troncoso, JC, Pirooznia, S, Andrabi, SA, Dawson, VL and Dawson, TM (2016) Adult conditional knockout of PGC-1alpha leads to loss of dopamine neurons. eNeuro 3(4), e0183-16.2016 1–8.Google Scholar
Kang, HJ, Voleti, B, Hajszan, T, Rajkowska, G, Stockmeier, CA, Licznerski, P, Lepack, A, Majik, MS, Jeong, LS, Banasr, M, Son, H and Duman, RS (2012) Decreased expression of synapse-related genes and loss of synapses in major depressive disorder. Nature Medicine 18, 14131417.Google Scholar
Karabatsiakis, A, Bock, C, Salinas-Manrique, J, Kolassa, S, Calzia, E, Dietrich, DE and Kolassa, IT (2014) Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression. Translational Psychiatry 4, e397.Google Scholar
Kato, N (2009) Neurophysiological mechanisms of electroconvulsive therapy for depression. Neuroscience Research 64, 311.Google Scholar
Kendler, KS, Neale, MC, MacLean, CJ, Heath, AC, Eaves, LJ and Kessler, RC (1993) Smoking and major depression. A causal analysis. Archives of General Psychiatry 50, 3643.Google Scholar
Khalaj, L, Nejad, SC, Mohammadi, M, Zadeh, SS, Pour, MH, Ahmadiani, A, Khodagholi, F, Ashabi, G, Alamdary, SZ and Samami, E (2013) Gemfibrozil pretreatment proved protection against acute restraint stress-induced changes in the male rats' hippocampus. Brain Research 1527, 117130.Google Scholar
Kim, MS, Sweeney, TR, Shigenaga, JK, Chui, LG, Moser, A, Grunfeld, C and Feingold, KR (2007) Tumor necrosis factor and interleukin 1 decrease RXRalpha, PPARalpha, PPARgamma, LXRalpha, and the coactivators SRC-1, PGC-1alpha, and PGC-1beta in liver cells. Metabolism 56, 267279.Google Scholar
Kim, SH, Koh, JH, Higashida, K, Jung, SR, Holloszy, JO and Han, DH (2015) PGC-1alpha mediates a rapid, exercise-induced downregulation of glycogenolysis in rat skeletal muscle. The Journal of Physiology 593, 635643.Google Scholar
Klinedinst, NJ and Regenold, WT (2015) A mitochondrial bioenergetic basis of depression. Journal of Bioenergetics and Biomembranes 47, 155171.Google Scholar
Kolshus, E, Ryan, KM, Blackshields, G, Smyth, P, Sheils, O and McLoughlin, DM (2017) Peripheral blood microRNA and VEGFA mRNA changes following electroconvulsive therapy: implications for psychotic depression. Acta Psychiatrica Scandinavica 136, 594606.Google Scholar
Labuzek, K, Liber, S, Gabryel, B and Okopien, B (2010) AICAR (5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside) increases the production of toxic molecules and affects the profile of cytokines release in LPS-stimulated rat primary microglial cultures. Neurotoxicology 31, 134146.Google Scholar
Liang, H and Ward, WF (2006) PGC-1alpha: a key regulator of energy metabolism. Advances in Physiology Education 30, 145151.Google Scholar
Lin, PY and Tseng, PT (2015) Decreased glial cell line-derived neurotrophic factor levels in patients with depression: a meta-analytic study. Journal of Psychiatric Research 63, 2027.Google Scholar
Lin, J, Wu, PH, Tarr, PT, Lindenberg, KS, St-Pierre, J, Zhang, CY, Mootha, VK, Jager, S, Vianna, CR, Reznick, RM, Cui, L, Manieri, M, Donovan, MX, Wu, Z, Cooper, MP, Fan, MC, Rohas, LM, Zavacki, AM, Cinti, S, Shulman, GI, Lowell, BB, Krainc, D and Spiegelman, BM (2004) Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell 119, 121135.Google Scholar
Lin, JD, Liu, C and Li, S (2008) Integration of energy metabolism and the mammalian clock. Cell Cycle 7, 453457.Google Scholar
Livak, KJ and Schmittgen, TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25, 402408.Google Scholar
Luo, XJ and Zhang, C (2016) Down-regulation of SIRT1 gene expression in major depressive disorder. The American Journal of Psychiatry 173, 1046.Google Scholar
Mootha, VK, Lindgren, CM, Eriksson, KF, Subramanian, A, Sihag, S, Lehar, J, Puigserver, P, Carlsson, E, Ridderstrale, M, Laurila, E, Houstis, N, Daly, MJ, Patterson, N, Mesirov, JP, Golub, TR, Tamayo, P, Spiegelman, B, Lander, ES, Hirschhorn, JN, Altshuler, D and Groop, LC (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nature Genetics 34, 267273.Google Scholar
Muller, N and Schwarz, MJ (2007) The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression. Molecular Psychiatry 12, 9881000.Google Scholar
Nierenberg, AA, Ghaznavi, SA, Mathias, IS, Ellard, KK, Janos, JA and Sylvia, LG (2018) Peroxisome proliferator activated receptor gamma co-activator-1 alpha as a novel target for bipolar disorder and other neuropsychiatric disorders. Biological Psychiatry 83, 761769.Google Scholar
Nijland, PG, Witte, ME, van het Hof, B, van der Pol, S, Bauer, J, Lassmann, H, van der Valk, P, de Vries, HE and van Horssen, J (2014) Astroglial PGC-1alpha increases mitochondrial antioxidant capacity and suppresses inflammation: implications for multiple sclerosis. Acta Neuropathologica Communications 2, 170.Google Scholar
Ogyu, K, Kubo, K, Noda, Y, Iwata, Y, Tsugawa, S, Omura, Y, Wada, M, Tarumi, R, Plitman, E, Moriguchi, S, Miyazaki, T, Uchida, H, Graff-Guerrero, A, Mimura, M and Nakajima, S (2018) Kynurenine pathway in depression: a systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews 90, 1625.Google Scholar
Polyakova, M, Schroeter, ML, Elzinga, BM, Holiga, S, Schoenknecht, P, de Kloet, ER and Molendijk, ML (2015) Brain-derived neurotrophic factor and antidepressive effect of electroconvulsive therapy: systematic review and meta-analyses of the preclinical and clinical literature. PLoS One 10, e0141564.Google Scholar
Puigserver, P, Wu, Z, Park, CW, Graves, R, Wright, M and Spiegelman, BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92, 829839.Google Scholar
Puigserver, P, Rhee, J, Donovan, J, Walkey, CJ, Yoon, JC, Oriente, F, Kitamura, Y, Altomonte, J, Dong, H, Accili, D and Spiegelman, BM (2003) Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature 423, 550555.Google Scholar
Qin, W, Haroutunian, V, Katsel, P, Cardozo, CP, Ho, L, Buxbaum, JD and Pasinetti, GM (2009) PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia. Archives of Neurology 66, 352361.Google Scholar
Rodgers, JT, Lerin, C, Haas, W, Gygi, SP, Spiegelman, BM and Puigserver, P (2005) Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 434, 113118.Google Scholar
Ryan, KM, Glaviano, A, O'Donovan, SM, Kolshus, E, Dunne, R, Kavanagh, A, Jelovac, A, Noone, M, Tucker, GM, Dunn, MJ and McLoughlin, DM (2017) Electroconvulsive therapy modulates plasma pigment epithelium-derived factor in depression: a proteomics study. Translational Psychiatry 7, e1073.Google Scholar
Rytinki, MM and Palvimo, JJ (2009) SUMOylation attenuates the function of PGC-1alpha. The Journal of Biological Chemistry 284, 2618426193.Google Scholar
Sajan, MP, Ivey, RA and Farese, RV (2015) BMI-related progression of atypical PKC-dependent aberrations in insulin signaling through IRS-1, Akt, FoxO1 and PGC-1alpha in livers of obese and type 2 diabetic humans. Metabolism 64, 14541465.Google Scholar
Schosser, A, Gaysina, D, Cohen-Woods, S, Domenici, E, Perry, J, Tozzi, F, Korszun, A, Gunasinghe, C, Gray, J, Jones, L, Binder, EB, Holsboer, F, Craddock, N, Owen, MJ, Craig, IW, Farmer, AE, Muglia, P and McGuffin, P (2011) A follow-up case-control association study of tractable (druggable) genes in recurrent major depression. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 156B, 640650.Google Scholar
Schuch, JB, Genro, JP, Bastos, CR, Ghisleni, G and Tovo-Rodrigues, L (2017) The role of CLOCK gene in psychiatric disorders: evidence from human and animal research. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 177, 181198.Google Scholar
Schwieler, L, Samuelsson, M, Frye, MA, Bhat, M, Schuppe-Koistinen, I, Jungholm, O, Johansson, AG, Landen, M, Sellgren, CM and Erhardt, S (2016) Electroconvulsive therapy suppresses the neurotoxic branch of the kynurenine pathway in treatment-resistant depressed patients. Journal of Neuroinflammation 13, 51.Google Scholar
Semkovska, M, Landau, S, Dunne, R, Kolshus, E, Kavanagh, A, Jelovac, A, Noone, M, Carton, M, Lambe, S, McHugh, C and McLoughlin, DM (2016) Bitemporal versus high-dose unilateral twice-weekly electroconvulsive therapy for depression (EFFECT-Dep): a pragmatic, randomized, non-inferiority trial. The American Journal of Psychiatry 173, 408417.Google Scholar
Simon, GE, Von Korff, M, Saunders, K, Miglioretti, DL, Crane, PK, van Belle, G and Kessler, RC (2006) Association between obesity and psychiatric disorders in the US adult population. Archives of General Psychiatry 63, 824830.Google Scholar
Soyal, SM, Felder, TK, Auer, S, Hahne, P, Oberkofler, H, Witting, A, Paulmichl, M, Landwehrmeyer, GB, Weydt, P, Patsch, W and European Huntington Disease Network (2012) A greatly extended PPARGC1A genomic locus encodes several new brain-specific isoforms and influences Huntington disease age of onset. Human Molecular Genetics 21, 34613473.Google Scholar
St-Pierre, J, Drori, S, Uldry, M, Silvaggi, JM, Rhee, J, Jager, S, Handschin, C, Zheng, K, Lin, J, Yang, W, Simon, DK, Bachoo, R and Spiegelman, BM (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127, 397408.Google Scholar
Sugden, MC, Caton, PW and Holness, MJ (2010) PPAR control: it's SIRTainly as easy as PGC. Journal of Endocrinology 204, 93104.Google Scholar
Takacs, M, Petoukhov, MV, Atkinson, RA, Roblin, P, Ogi, FX, Demeler, B, Potier, N, Chebaro, Y, Dejaegere, A, Svergun, DI, Moras, D and Billas, IM (2013) The asymmetric binding of PGC-1alpha to the ERRalpha and ERRgamma nuclear receptor homodimers involves a similar recognition mechanism. PLoS One 8, e67810.Google Scholar
Tang, K, Wagner, PD and Breen, EC (2010) TNF-alpha-mediated reduction in PGC-1alpha may impair skeletal muscle function after cigarette smoke exposure. Journal of Cellular Physiology 222, 320327.Google Scholar
Thau, N, Knippenberg, S, Korner, S, Rath, KJ, Dengler, R and Petri, S (2012) Decreased mRNA expression of PGC-1alpha and PGC-1alpha-regulated factors in the SOD1G93A ALS mouse model and in human sporadic ALS. Journal of Neuropathology and Experimental Neurology 71, 10641074.Google Scholar
Tritos, NA, Mastaitis, JW, Kokkotou, EG, Puigserver, P, Spiegelman, BM and Maratos-Flier, E (2003) Characterization of the peroxisome proliferator activated receptor coactivator 1 alpha (PGC 1alpha) expression in the murine brain. Brain Research 961, 255260.Google Scholar
Tseng, PT, Cheng, YS, Chen, YW, Wu, CK and Lin, PY (2015) Increased levels of vascular endothelial growth factor in patients with major depressive disorder: a meta-analysis. European Neuropsychopharmacology 25, 16221630.Google Scholar
UK ECT Review Group (2003) Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 361, 799808.Google Scholar
Vega, RB, Huss, JM and Kelly, DP (2000) The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Molecular and Cellular Biology 20, 18681876.Google Scholar
Villena, JA (2015) New insights into PGC-1 coactivators: redefining their role in the regulation of mitochondrial function and beyond. The FEBS Journal 282, 647672.Google Scholar
Wang, Q and Dwivedi, Y (2017) Transcriptional profiling of mitochondria associated genes in prefrontal cortex of subjects with major depressive disorder. The World Journal of Biological Psychiatry 18, 592603.Google Scholar
Weydt, P, Soyal, SM, Landwehrmeyer, GB, Patsch, W and European Huntington Disease Network (2014) A single nucleotide polymorphism in the coding region of PGC-1alpha is a male-specific modifier of Huntington disease age-at-onset in a large European cohort. BMC Neurology 14, 1.Google Scholar
World Health Organisation (2017) Depression and Other Common Mental Disorders: Global Health Estimates. Geneva: World Health Organisation. Available at http://apps.who.int/iris/bitstream/10665/254610/1/WHO-MSD-MER-2017.2-eng.pdf?ua=1.Google Scholar
World Medical Association (2013) World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310, 21912194.Google Scholar
Yrondi, A, Sporer, M, Peran, P, Schmitt, L, Arbus, C and Sauvaget, A (2018) Electroconvulsive therapy, depression, the immune system and inflammation: a systematic review. Brain Stimulation 11, 2951.Google Scholar
Zaki, NFW, Spence, DW, BaHammam, AS, Pandi-Perumal, SR, Cardinali, DP and Brown, GM (2017) Chronobiological theories of mood disorder. European Archives of Psychiatry and Clinical Neuroscience 268, 107118.Google Scholar
Supplementary material: File

Ryan supplementary material

Table S1

Download Ryan supplementary material(File)
File 19.6 KB
Supplementary material: File

Ryan supplementary material

Table S2

Download Ryan supplementary material(File)
File 15.5 KB