Metabolic signature in nucleus accumbens for anti-depressant-like effects of 1 acetyl-L-carnitine 2 3 4

7 8 1 Laboratory for Functional and Metabolic Imaging (LIFMET), École Polytechnique Fédérale de 9 Lausanne (EPFL), Lausanne, Switzerland 10 2 Laboratory of Behavioral Genetics, Brain and Mind Institute, School of Life Sciences, Ecole 11 Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. 12 3 Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 13 New York, USA 14 4 Center for Psychiatric Neurosciences, Lausanne University Hospital (CHUV), Site de Cery, Lausanne, 15 Switzerland. 16 17 18 Running title: Effect of LAC against stress-induced depression 19

[1]  Marwa N. Atallah,et al.  Protective effects of Zingiber officinale extract on myocardium and placenta against labetalol-induced histopathological, immune-histochemical, and ultrastructural alterations in pregnant rats , 2021, The Journal of Basic and Applied Zoology.

[2]  D. Vance.  Phosphatidylcholine Metabolism , 2020 .

[3]  Zachary S. Lorsch,et al.  Multidimensional Predictors of Susceptibility and Resilience to Social Defeat Stress , 2019, Biological Psychiatry.

[4]  M. Molendijk,et al.  Coping with the forced swim stressor , 2019, Psychoneuroendocrinology.

[5]  F. Gage,et al.  Mitochondria, Metabolism, and Redox Mechanisms in Psychiatric Disorders. , 2019, Antioxidants & redox signaling.

[6]  Ricieri Mocelin,et al.  Acetyl-L-carnitine as a putative candidate for the treatment of stress-related psychiatric disorders: Novel evidence from a zebrafish model , 2019, Neuropharmacology.

[7]  M. Müller,et al.  Chronic social stress-induced hyperglycemia in mice couples individual stress susceptibility to impaired spatial memory , 2018, Proceedings of the National Academy of Sciences.

[8]  B. McEwen,et al.  Acetyl-l-carnitine deficiency in patients with major depressive disorder , 2018, Proceedings of the National Academy of Sciences.

[9]  C. Sandi,et al.  Stress‐Induced Depression: Is Social Rank a Predictive Risk Factor? , 2018, BioEssays : news and reviews in molecular, cellular and developmental biology.

[10]  A. Nierenberg,et al.  Mitochondrial Dysfunction: At the Core of Psychiatric Disorders? , 2018, Biological Psychiatry.

[11]  G. Richter-Levin,et al.  How could stress lead to major depressive disorder? , 2018, IBRO reports.

[12]  M. Weger,et al.  High anxiety trait: A vulnerable phenotype for stress-induced depression , 2018, Neuroscience & Biobehavioral Reviews.

[13]  D. Wallace,et al.  Mitochondrial Etiology of Neuropsychiatric Disorders , 2017, Biological Psychiatry.

[14]  A. Carvalho,et al.  Acetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis , 2017, Psychosomatic medicine.

[15]  C. Sandi,et al.  Diazepam actions in the VTA enhance social dominance and mitochondrial function in the nucleus accumbens by activation of dopamine D1 receptors , 2017, Molecular Psychiatry.

[16]  P. Greengard,et al.  Role of the Astroglial Glutamate Exchanger xCT in Ventral Hippocampus in Resilience to Stress , 2017, Neuron.

[17]  Rolf Gruetter,et al.  Hierarchical Status Predicts Behavioral Vulnerability and Nucleus Accumbens Metabolic Profile Following Chronic Social Defeat Stress , 2017, Current Biology.

[18]  M. McKenna,et al.  l-Carnitine and Acetyl-l-carnitine Roles and Neuroprotection in Developing Brain , 2017, Neurochemical Research.

[19]  M. Friedrich.  Depression Is the Leading Cause of Disability Around the World. , 2017, JAMA.

[20]  M. Lobo,et al.  Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression , 2017, Biological Psychiatry.

[21]  Faezeh Jafari,et al.  Taurine treatment preserves brain and liver mitochondrial function in a rat model of fulminant hepatic failure and hyperammonemia. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[22]  P. Svenningsson,et al.  Epigenetics and energetics in ventral hippocampus mediate rapid antidepressant action: Implications for treatment resistance , 2016, Proceedings of the National Academy of Sciences.

[23]  A. Mishra,et al.  ALCAR Exerts Neuroprotective and Pro-Neurogenic Effects by Inhibition of Glial Activation and Oxidative Stress via Activation of the Wnt/β-Catenin Signaling in Parkinsonian Rats , 2015, Molecular Neurobiology.

[24]  Carla Nasca,et al.  Mechanisms of stress in the brain , 2015, Nature Neuroscience.

[25]  Y. Lu,et al.  Rapid-acting antidepressant-like effects of acetyl-l-carnitine mediated by PI3K/AKT/BDNF/VGF signaling pathway in mice , 2015, Neuroscience.

[26]  E. Morava,et al.  Mitochondria and the economy of stress (mal)adaptation , 2013, Neuroscience & Biobehavioral Reviews.

[27]  Aaron S. Andalman,et al.  Dopamine neurons modulate neural encoding and expression of depression-related behaviour , 2012, Nature.

[28]  C. Sandi,et al.  Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity , 2012, Psychoneuroendocrinology.

[29]  K. Bhakoo.  N-Acetyl-Aspartate (NAA) Metabolism , 2012 .

[30]  G. Martinotti,et al.  Acetyl-l-Carnitine in the treatment of anhedonia, melancholic and negative symptoms in alcohol dependent subjects , 2011, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[31]  B. McEwen.  Stress-Induced Structural and Functional Plasticity in the Brain: Protection, Damage, and Brain–Body Communication , 2011 .

[32]  Carmen Sandi,et al.  From high anxiety trait to depression: a neurocognitive hypothesis , 2009, Trends in Neurosciences.

[33]  S. Yousuf,et al.  Restraint stress-induced oxidative damage and its amelioration with selenium. , 2008, European journal of pharmacology.

[34]  D. Diamond,et al.  Hyperglycemia not hypoglycemia alters neuronal dendrites and impairs spatial memory , 2008, Pediatric diabetes.

[35]  R. Turner,et al.  Stress burden and the lifetime incidence of psychiatric disorder in young adults: racial and ethnic contrasts. , 2004, Archives of general psychiatry.

[36]  Arne Schousboe,et al.  Compartmentation of Glutamine, Glutamate, and GABA Metabolism in Neurons and Astrocytes: Functional Implications , 2003, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[37]  Masao Iwase,et al.  Brain Regions Involved in Fatigue Sensation: Reduced Acetylcarnitine Uptake into the Brain , 2002, NeuroImage.

[38]  D. Servan-Schreiber,et al.  31P-MRS study of acetyl-L-carnitine treatment in geriatric depression: preliminary results. , 2002, Bipolar disorders.

[39]  S. Provencher.  Automatic quantitation of localized in vivo 1H spectra with LCModel , 2001, NMR in biomedicine.

[40]  J. Pettegrew,et al.  Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression , 2000, Molecular Psychiatry.

[41]  R Gruetter,et al.  Field mapping without reference scan using asymmetric echo‐planar techniques , 2000, Magnetic resonance in medicine.

[42]  J. Klein.  Membrane breakdown in acute and chronic neurodegeneration: focus on choline-containing phospholipids , 2000, Journal of Neural Transmission.

[43]  不破 相勲,et al.  脳回肥厚症の^1H-NMR spectroscopy , 1998 .

[44]  B. Siesjö,et al.  Calcium in ischemic cell death. , 1998, Stroke.

[45]  P. Magistretti,et al.  Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[46]  H. Quinney,et al.  Carnitine stimulation of glucose oxidation in the fatty acid perfused isolated working rat heart. , 1992, The Journal of biological chemistry.

[47]  F. Drago,et al.  Acetylcarnitine reduces the immobility of rats in a despair test (constrained swim). , 1990, Behavioral and neural biology.

[48]  A. Miccheli,et al.  Aging brain: effect of acetyl-l-carnitine treatment on rat brain energy and phospholipid metabolism. A study by31P and1H NMR spectroscopy , 1990, Brain Research.

[49]  M. Norenberg,et al.  Fine structural localization of glutamine synthetase in astrocytes of rat brain , 1979, Brain Research.