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Coadministration of tianeptine alters behavioral parameters and levels of neurotrophins in a chronic model of Maple Syrup Urine disease

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Abstract

Maple Syrup Urine Disease (MSUD) is caused by the deficiency in the activity of the branched-chain α-ketoacid dehydrogenase complex (BCKDC), resulting in the accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine, and their respective branched-chain α-keto acids. Patients with MSUD are at high risk of developing chronic neuropsychiatric disorders; however, the pathophysiology of brain damage in these patients remains unclear. We hypothesize that MSUD can cause depressive symptoms in patients. To test our hypothesis, Wistar rats were submitted to the BCAA and tianeptine (antidepressant) administration for 21 days, starting seven days postnatal. Depression-like symptoms were assessed by testing for anhedonia and forced swimming after treatments. After the last test, the brain structures were dissected for the evaluation of neutrophins. We demonstrate that chronic BCAA administration induced depressive-like behavior, increased BDNF levels, and decreased NGF levels, suggesting a relationship between BCAA toxicity and brain damage, as observed in patients with MSUD. However, the administration of tianeptine was effective in preventing behavioral changes and restoring neurotrophins levels.

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Data Availability

The data that support the findings of this study are available on request from the corresponding author.

References

  • Alamo C, García-Garcia P, Lopez-Muñoz F, Zaragozá C (2009) Tianeptine, an atypical pharmacological approach to depression. Rev Psiquiatr Salud Ment (Engl Ed). 12:170-186

  • Alfonso J, Frick LR, Silberman DM, Palumbo ML, Genaro AM, Frasch AC (2006) Regulation of hippocampal gene expression is conserved in two species subjected to different stressors and antidepressant treatments. Biol Psychiatry 59(3):244–251

    Article  CAS  PubMed  Google Scholar 

  • Autry AE, Monteggia LM (2012) Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 64(2):238–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bibel M, Barde YA (2000) Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev 14:2919–2937

    Article  CAS  PubMed  Google Scholar 

  • Bonfils J, Faure M, Gibrat JF, Glomot F, Papet I (2000) Sheep cytosolic branched-chain amino acid aminotransferase: cDNA cloning, primary structure and molecular modelling and its unique expression in muscles. Biochim Biophys Acta 1494:129–136

    Article  CAS  PubMed  Google Scholar 

  • Bonhoeffer T (1996) Neurotrophins and activity-dependent development of the neocortex. Curr Opin Neurobiol 6:119–126

    Article  CAS  PubMed  Google Scholar 

  • Bouchereau J, Leduc-Leballeur J, Pichard S, Imbard A, Benoist JF, Abi Warde MT, Arnoux JB, Barbier V, Brassier A, Broué P, Cano A, Chabrol B, Damon G, Gay C, Guillain I, Habarou F, Lamireau D, Ottolenghi C, Paermentier L, Sabourdy F, Touati G, Ogier de Baulny H, de Lonlay P, Schiff M (2017) Neurocognitive profiles in MSUD schoolage patients. J Inherit Metab Dis. 40:377–383

  • Bridi R, Fontella FU, Pulrolnik V, Braun CA, Zorzi GK, Coelho D, Wajner M, Vargas CR, Dutra-Filho CS (2006) A chemically-induced acute model of maple syrup urine disease in rats for neurochemical studies. J Neurosci Methods 155:224–230

    Article  CAS  PubMed  Google Scholar 

  • Canossa M, Gärtner A, Campana G, Inagaki N, Thoenen H (2001) Regulated secretion of neurotrophins by metabotropic glutamate group I (mGluRI) and Trk receptor activation is mediated via phospholipase C signalling pathways. EMBO J. 20:1640–1650

  • Carvalho AL, Caldeira MV, Santos SD, Duarte CB (2008) Role of the brain-derived neurotrophic factor at glutamatergic synapses. Br J Pharmacol 153:S310–S324

    Article  CAS  PubMed  Google Scholar 

  • Castells AA, Gueraldi D, Balada R, Tristán-Noguero A, Cortès-Saladelafont E, Ramos F, Meavillaa S, De Los Santos M, Garcia-Volpe C, Colomé R, Couce ML, Sierra C, Ormazábal A, Batllori M, Artuch R, Armstrong J, Alcántara S, Garcia-Cazorla À (2019) Discovery of Biomarker Panels for Neural Dysfunction in Inborn Errors of Amino Acid Metabolism. Sci Rep 9:9128.

  • Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J et al (2008) MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320(5880):1224–1229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chuang DT, Shih VE (2001) Maple syrup urine diasese (branched-chain ketoaciduria). In: Scriver, CR, Beaudt AL, Sly WL, Valle D, editores. The metabolic and Molecular Bases of Iheritd Disease. 8 ed. New York: Mc Graw-Hill

  • Conrad CD, Galea LA, Kuroda Y, McEwen BS (1996) Chronic stress impairs rat spatial memory on the Y maze, and this effect is blocked by tianeptine pretreatment. Behav Neurosci 110:1321–1334

    Article  CAS  PubMed  Google Scholar 

  • Croll SD, Suri C, Compton DL (1999) Brain-derived neurotrophic factor transgenic mice exhibit passive avoidance deficits, increased seizure severity and in vitro hyperexcitability in the hippocampus and entorhinal cortex. Neuroscience 93:1491–1506

    Article  CAS  PubMed  Google Scholar 

  • Cunha C, Angelucci A, D’Antoni A (2009) Brain-derived neurotrophic factor (BDNF) overexpression in the forebrain results in learning and memory impairments. Neurobiol Dis 33:358–368

    Article  CAS  PubMed  Google Scholar 

  • Czéh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M, Bartolomucci A, Fuchs E (2001) Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci U S A. 98:12796-12801

  • Danner DJ, Elsas LJ (1989) Disorders of branched chain amino acids and keto acid metabolism. In: Scriver, CR, Beaudet AL, Sly WS, Valle D, editores. The metabolic basis of inherited disease. 6 ed. New York: McGraw-Hill

  • Dean J, Keshavan M (2017) The neurobiology of depression: An integrated view. Asian J Psychiatr 27:101–111

    Article  PubMed  Google Scholar 

  • Della FP, Abelaira HM, Réus GZ, Ribeiro KF, Antunes AR, Scaini G, Jeremias IC, dos Santos LM, Jeremias GC, Streck EL, Quevedo J (2012) Tianeptine treatment induces antidepressive-like effects and alters BDNF and energy metabolism in the brain of rats. Behav Brain Res 233(2):526–535. https://doi.org/10.1016/j.bbr.2012.05.039

    Article  CAS  PubMed  Google Scholar 

  • Della FP, Abelaira HM, Réus GZ, Santos MA, Tomaz DB, Antunes AR, Scaini G, Morais MO, Streck EL, Quevedo J (2013) Treatment with tianeptine induces antidepressive-like effects and alters the neurotrophin levels, mitochondrial respiratory chain and cycle Krebs enzymes in the brain of maternally deprived adult rats. Metab Brain Dis 28(1):93–105

    Article  CAS  PubMed  Google Scholar 

  • Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 59(12):1116–27

    Article  CAS  PubMed  Google Scholar 

  • Dwivedi Y (2013) Involvement of brain derived neurotrophic factor in late-life depression. Am J Geriatr Psychiatry 21(5):433–449

    Article  PubMed  PubMed Central  Google Scholar 

  • Figurov A, Pozzo-Miller LD, Olafsson P, Wang T, Lu B (1996) Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Nature 381:706–709

    Article  CAS  PubMed  Google Scholar 

  • Gamaro GD, Manoli LP, Torres IL, Silveira R, Dalmaz C (2003) Effects of chronic variate stress on feeding behavior and on monoamine levels in different rat brain structures. Neurochem Int 42:107–114

    Article  CAS  PubMed  Google Scholar 

  • Gnahn H, Hefti F, Heumann R, Schwab ME, Thoenen H (1983) NGF-mediated increase of choline acetyltransferase (ChAT) in the neonatal rat forebrain: evidence for a physiological role of NGF in the brain? Brain Res 285:45–52

    Article  CAS  PubMed  Google Scholar 

  • Gu H, Long D, Song C, Li X (2009) Recombinant human NGF-loaded microspheres promote survival of basal forebrain cholinergic neurons and improve memory impairments of spatial learning in the rat model of Alzheimer’s disease with fimbria-fornix lesion. Neurosci Lett 453:204–209. https://doi.org/10.1016/j.neulet.2009.02.027

    Article  CAS  PubMed  Google Scholar 

  • Guillin O, Diaz J, Carroll P, Griffon N, Schwartz JC, Sokoloff P (2001) BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization. Nature 411:86–89

    Article  CAS  PubMed  Google Scholar 

  • Gulyaeva NV (2017) Interplay between brain BDNF and Glutamatergic Systems: A Brief State of the Evidence and Association with the Pathogenesis of Depression. Biochemistry (mosc) 82(3):301–307

    Article  CAS  Google Scholar 

  • Gwag BJ, Koh JY, Chen MM (1995) BDNF or IGF-I potentiates free radical-mediated injury in cortical cell cultures. NeuroReport 7:93–96

    Article  CAS  PubMed  Google Scholar 

  • Han J, Andreu V, Langreck C, Pekarskaya EA, Grinnell SG, Allain F, Magalong V, Pintar J, Kieffer BL, Harris AZ, Javitch JA, Hen R, Nautiyal KM (2021) Mu opioid receptors on hippocampal GABAergic interneurons are critical for the antidepressant effects of tianeptine. Neuropsychopharmacology. https://doi.org/10.1038/s41386-021-01192-2

  • Hanson JL, Knodt AR, Brigidi BD, Hariri AR (2015) Lower structural integrity of the uncinate fasciculus is associated with a history of child maltreatment and future psychological vulnerability to stress. Dev Psychopathol 27(4 Pt 2):1611–1619. https://doi.org/10.1017/S0954579415000978

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang EJ, Reichardt LF (2001) Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 24:677–736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang EJ, Reichardt LF (2003) Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem 72:609–642

    Article  CAS  PubMed  Google Scholar 

  • Hutson SM, Lieth E, LaNoue KF (2001) Function of leucine in excitatory neurotrasmitter metabolism in the central nervous system. J Nutr 131(3):846S-850S

    Article  CAS  PubMed  Google Scholar 

  • Jantas D, Krawczyk S, Lason W (2014) The Predominant Protective Effect of Tianeptine Over Other Antidepressants in Models of Neuronal Apoptosis: The Effect Blocked by Inhibitors of MAPK/ERK1/2 and PI3-K/Akt Pathways. Neurotox Res 25:208–225

    Article  CAS  PubMed  Google Scholar 

  • Kandratavicius L, Monteiro MR, do Val-da Silva RA, Leite JP (2010) Neurotrofinas na epilepsia do lobo temporal. J Epilepsy Clin Neurophysiol 16(1):7–12

    Article  Google Scholar 

  • Jean, Y, Lercher L, Dreyfus C (2008) Glutamate elicits release of BDNF from basal forebrain astrocytes in a process dependent on metabotropic receptors and the PLC pathway. Neuron Glia Biology, 4:35-42

  • Katz RJ, Roth KA (1981b) Carroll BJ Animal models and human depressive disorders. Neurosci Biobehav Rev 5:231–246

    Article  CAS  PubMed  Google Scholar 

  • Katz RJ, Roth KA, Carroll BJ (1981a) Acute and chronic stress effects on open field activity in the rat: implications for a model of depression. Neurosci Biobehav Rev 5:247–251

    Article  CAS  PubMed  Google Scholar 

  • Keefe KM, Sheikh IS, Smith GM (2017) Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury. Int J Mol Sci. 18:548

  • Klein RL, Hirko AC, Meyers CA, Grimes JR, Muzyczka N, Meyer EM (2000) NGF gene transfer to intrinsic basal forebrain neurons increases cholinergic cell size and protects from age-related, spatial memory deficits in middle-aged rats. Brain Res 875:144–151

    Article  CAS  PubMed  Google Scholar 

  • Korte M, Carroll P, Wolf E, Brem G, Thoenen H, Bonhoeffer T (1995) Hippocampal long-term potentiation is impaired in mice lacking brainderived neurotrophic factor. Proc Natl Acad Sci U S A 92(8856–8860):41066

    Google Scholar 

  • Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature 455:894–902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee R, Kermani P, Teng KK, Hempstead BL (2001) Regulation of cell survival by secreted proneurotrophins. Science 294:1945–1948

    Article  CAS  PubMed  Google Scholar 

  • Lessmann V, Gottmann K, Malcangio M (2003) Neurotrophin secretion: current facts and future prospects. Prog Neurobiol. 69(5):341–74

    Article  CAS  PubMed  Google Scholar 

  • León A, Gibon J, Barker PA (2021) NGF-Dependent and BDNF-Dependent DRG Sensory Neurons Deploy Distinct Degenerative Signaling Mechanisms. eNeuro 8:ENEURO.0277-20.2020

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265

    Article  CAS  PubMed  Google Scholar 

  • Lu Y, Christian K, Lu B (2008) BDNF: a key regulator for protein synthesis-dependent LTP and longterm memory? Neurobiol Learn Mem 89:312–323

    Article  CAS  PubMed  Google Scholar 

  • Lu B, Pang PT, Woo NH (2005) The yin and yang of neurotrophin action. Nat Rev Neurosci 6:603–614

    Article  CAS  PubMed  Google Scholar 

  • Luine V, Villegas M, Martinez C, McEwen BS (1994) Repeated stress causes reversible impairments of spatial memory performance. Brain Res 639:167–170

    Article  CAS  PubMed  Google Scholar 

  • Magariños AM, Deslandes A, McEwen BS (1999) Effects of antidepressants and benzodiazepine treatments on the dendritic structure of CA3 pyramidal neurons after chronic stress. Eur J Pharmacol. 371:113-122

  • McAllister AK, Katz LC, Lo DC (1999) Neurotrophins and synaptic plasticity. Annu Rev Neurosci 22:295–318

    Article  CAS  PubMed  Google Scholar 

  • McEwen BS, Chattarji S, Diamond DM, Jay TM, Reagan LP, Svenningsson P, Fuchs E (2010) The neurobiological properties of Tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation. Mol Psychiatry 15(3):237–249

    Article  CAS  PubMed  Google Scholar 

  • Mendell LM, Munson JB, Arvanian VL (2001) Neurotrophins and synaptic plasticity in the mammalian spinal cord. J Physiol 533:91–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Molteni R, Calabrese F, Chourbaji S, Brandwein C, Racagni G, Gass P, Riva MA (2010) Depression-prone mice with reduced glucocorticoid receptor expression display an altered stress-dependent regulation of brain-derived neurotrophic factor and activity-regulated cytoskeleton-associated protein. J Psychopharm 24(4):595595–595603

    Article  Google Scholar 

  • Morley-Fletcher S, Darnaudery M, Koehl M, Casolini P, Van Reeth O, Maccari S (2003) Prenatal stress in rats predicts immobility behavior in the forced swim test. Effects of a chronic treatment with tianeptine. Brain Res. 989(2):246–51

    Article  CAS  PubMed  Google Scholar 

  • Morris RG, Kelly S, Burney D, Anthony T, Boyer PA, Spedding M (2001) Tianeptine and its enantiomers: effects on spatial memory in rats with medial septum lesions. Neuropharmacology 41:272–281

    Article  CAS  PubMed  Google Scholar 

  • Mossner R, Daniel S, Albert D, Heils A, Okladnova O, Schmitt A, Lesch KP (2000) Serotonin transporter function is modulated by brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF). Neurochem Int 36:197–202

    Article  CAS  PubMed  Google Scholar 

  • Mu JS, Li WP, Yao ZB, Zhou XF (1999) Deprivation of endogenous brain-derived neurotrophic factor results in impairment of spatial learning and memory in adult rats. Brain Res 835:259–265

    Article  CAS  PubMed  Google Scholar 

  • Muelly ER, Moore GJ, Bunce SC, Mack J, Bigler DC, Morton DH, Strauss KA (2013) Biochemical correlates of neuropsychiatric illness in maple syrup urine disease. J Clin Invest 123(4):1809–1820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagahara AH, Bernot T, Moseanko R, Brignolo L, Blesch A, Conner JM, Ramirez A, Gasmi M, Tuszynski MH (2009) Long-term reversal of cholinergic neuronal decline in aged non-human primates by lentiviral NGF gene delivery. Exp Neurol 215(1):153–159. https://doi.org/10.1016/j.expneurol.2008.10.004

    Article  CAS  PubMed  Google Scholar 

  • Nestler EJ, Gould E, Manji H, Buncan M, Duman RS, Greshenfeld HK, Hen R, Koester S, Lederhendler I, Meaney M, Robbins T, Winsky L, Zalcman S (2002) Preclinical model: status of basic research in depression. Biol Psychiatry 52:503–528

    Article  PubMed  Google Scholar 

  • Patterson SL, Abel T, Deuel TA, Martin KC, Rose JC, Kandel ER (1996) Recombinant BDNF rescues deficits in basal synaptic transmission and hippocampal LTP in BDNF knockout mice. Neuron 16:1137–1145

    Article  CAS  PubMed  Google Scholar 

  • Perić I, Stanisavljević A, Inta D, Gass P, Lang UE, Borgwardt S, Filipović D (2019) Tianeptine antagonizes the reduction of PV+ and GAD67 cells number in dorsal hippocampus of socially isolated rats. Prog Neuropsychopharmacol Biol Psychiatry 89:386–399

    Article  PubMed  CAS  Google Scholar 

  • Porsolt RD, Le Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 21:266–730

    Google Scholar 

  • Poon CH, Heng BC, Lim LW (2021) New insights on brain-derived neurotrophic factor epigenetics: from depression to memory extinction. Ann N Y Acad Sci. 1484:9-31

  • Pothos EM (1995) Restricted eating with weight loss selectively decreases extracellular dopamine in the nucleus accumbes and alters dopamine responses to amphetamine, morphine, and food intake. J Neurosci 15:6640–6650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rantamäki T, Kemppainen S, Autio H, Stavén S, Koivisto H, Kojima M, Antila H, Miettinen PO, Kärkkäinen E, Karpova N, Vesa L, Lindemann L, Hoener MC, Tanila H, Castrén E (2013) The impact of Bdnf gene deficiency to the memory impairment and brain pathology of APPswe/PS1dE9 mouse model of Alzheimer’s disease. PLoS ONE 8(7):e68722. https://doi.org/10.1371/journal.pone.0068722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reagan LP, Hendry RM, Reznikov LR, Piroli GG, Wood GE, McEwen BS et al (2007) Tianeptine increases brain-derived neurotrophic factor expression in the rat amygdala. Eur J Pharmacol 565(1–3):68–75

    Article  CAS  PubMed  Google Scholar 

  • Reichardt LF (2006) Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond Ser B Biol Sci 361:1545–1564. https://doi.org/10.1098/rstb.2006.1894

    Article  CAS  Google Scholar 

  • Scaini G, Comim CM, Oliveira GM, Pasquali MA, Quevedo J, Gelain DP, Moreira JC, Schuck PF, Ferreira GC, Bogo MR, Streck EL (2013a) Chronic administration of branched-chain amino acids impairs spatial memory and increases brain-derived neurotrophic factor in a rat model. J Inherit Metab Dis 36(5):721–730. https://doi.org/10.1007/s10545-012-9549-z

    Article  CAS  PubMed  Google Scholar 

  • Scaini G, Jeremias GC, Furlanetto CB, Dominguini D, Comim CM, Quevedo J, Schuck PF, Ferreira GC, Streck EL (2014) Behavioral Responses in Rats Submitted to Chronic Administration of Branched-Chain Amino Acids. JIMD Rep. 13:159–67. https://doi.org/10.1007/8904_2013_274

    Article  PubMed  Google Scholar 

  • Scaini G, Mello-Santos LM, Furlanetto CB, Jeremias IC, Mina F, Schuck PF, Ferreira GC, Kist LW, Pereira TC, Bogo MR, Streck EL (2013b) Acute and chronic administration of the branched-chain amino acids decreases nerve growth factor in rat hippocampus. Mol Neurobiol 48(3):581–589. https://doi.org/10.1007/s12035-013-8447-1

    Article  CAS  PubMed  Google Scholar 

  • Scaini G, Morais MO, Furlanetto CB, Kist LW, Pereira TC, Schuck PF, Ferreira GC, Pasquali MA, Gelain DP, Moreira JC, Bogo MR, Streck EL (2015) Acute Administration of Branched-Chain Amino Acids Increases the Pro-BDNF/Total-BDNF Ratio in the Rat Brain. Neurochem Res 40(5):885–893. https://doi.org/10.1007/s11064-015-1541-1

    Article  CAS  PubMed  Google Scholar 

  • Scaini G, Teodorak BP, Jeremias IC, Morais MO, Mina F, Dominguini D, Pescador B, Comim CM, Schuck PF, Ferreira GC, Quevedo J, Streck EL (2012) Antioxidant administration prevents memory impairment in an animal model of maple syrup urine disease. Behav Brain Res. 231(1):92–6. https://doi.org/10.1016/j.bbr.2012.03.004

    Article  CAS  PubMed  Google Scholar 

  • Scaini G, Tonon T, de Souza CFM, Schuk PF, Ferreira GC, Neto JS, Amorim T, Schwartz IVD, Streck EL (2017) Serum Markers of Neurodegeneration in Maple Syrup Urine Disease. Mol Neurobiol 54(7):5709–5719. https://doi.org/10.1007/s12035-016-0116-8

    Article  CAS  PubMed  Google Scholar 

  • Schmidt HD, Duman RS (2007) The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior. Behav Pharmacol 18(5–6):391–418

    Article  CAS  PubMed  Google Scholar 

  • Solich J, Pałach P, Budziszewska B, Dziedzicka-Wasylewska M (2008) Effect of two behavioral tests on corticosterone level in plasma of mice lacking the noradrenaline transporter. Pharmacol Rep. 60(6):1008–13

    CAS  PubMed  Google Scholar 

  • Skaper SD (2018) Neurotrophic Factors: An Overview. Methods Mol Biol 1727:1–17. https://doi.org/10.1007/978-1-4939-7571-6_1

    Article  CAS  PubMed  Google Scholar 

  • Strauss KA, Puffenberger EG, Morton DH (2006) Maple syrup urine disease. In: Pagon R, Bird T, Dolan C, Stephens, K, Adam, M eds. GeneReviews. Seattle, Washington, USA: University of Washington

  • Strauss KA, Wardley B, Robinson D, Hendrickson C, Rider NL, Puffenberger EG, Shellmer D, Moser AB, Morton DH (2010) Classical maple syrup urine disease and brain development: principles of management and formula design. Mol Genet Metab 99(4):333–345. https://doi.org/10.1016/j.ymgme.2009.12.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taschetto L, Scaini G, Zapelini HG, Ramos ÂC, Strapazzon G, Andrade VM, Réus GZ, Michels M, Dal-Pizzol F, Quevedo J, Schuck PF, Ferreira GC, Streck EL (2017) Acute and long-term effects of intracerebroventricular administration of α-ketoisocaproic acid on oxidative stress parameters and cognitive and noncognitive behaviors. Metab Brain Dis 32(5):1507–1518. https://doi.org/10.1007/s11011-017-0035-z

    Article  CAS  PubMed  Google Scholar 

  • Taylor S, Srinivasan B, Wordinger RJ, Roque RS (2003) Glutamate stimulates neurotrophin expression in cultured Müller cells. Brain Res Mol Brain Res. 111:189-197

  • Uzbay TI (2008) Tianeptine: potential influences on neuroplasticity and novel pharmacological effects. Prog Neuropsychopharmacol Biol Psychiatry. 32:915-924

  • Uzbekov MG (2009) Antidepressant action of tianeptine is connected with acceleration of serotonin turnover in the synapse: a hypothesis. Neuropsychopharmacol Hung 11(2):83–87

    PubMed  Google Scholar 

  • Vuković O, Marić NP, Britvić D, Cvetić T, Damjanović A, Prostran M, Jasović-Gasić M (2009) Efficacy, tolerability and safety of tianeptine in special populations of depressive patients. Psychiatr Danub. 21:194–198.

  • Wisniewski MS, Carvalho-Silva M, Gomes LM, Zapelini HG, Schuck PF, Ferreira GC, Scaini G, Streck EL (2016) Intracerebroventricular administration of α-ketoisocaproic acid decreases brain-derived neurotrophic factor and nerve growth factor levels in brain of young rats. Metab Brain Dis 31(2):377–383. https://doi.org/10.1007/s11011-015-9768-8

    Article  CAS  PubMed  Google Scholar 

  • Wlaź P, Kasperek R, Wlaź A, Szumiło M, Wróbel A, Nowak G, Poleszak E (2011) NMDA and AMPA receptors are involved in the antidepressant-like activity of tianeptine in the forced swim test in mice. Pharmacol Rep. 63:1526–1532

  • Woo NH, Teng HK, Siao CJ (2005) Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat Neurosci 8:1069–1077

    Article  CAS  PubMed  Google Scholar 

  • Xu J, Jakher Y, Ahrens-Nicklas RC (2020) Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders. Int J Mol Sci. 21:7490

  • Zoladz PR, Park CR, Muñoz C, Fleshner M, Diamond DM (2008) Tianeptine: An Antidepressant with Memory-Protective Properties. Curr Neuropharmacol 6:311–321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zoladz PR, Muñoz C, Diamond DM (2010) Beneficial Effects of Tianeptine on Hippocampus-Dependent Long-Term Memory and Stress-Induced Alterations of Brain Structure and Function. Pharmaceuticals 3:3143–3166

    Article  CAS  PubMed Central  Google Scholar 

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Funding

This research was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Universidade do Extremo Sul Catarinense (UNESC).

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Morais, F.A., Lemos, I.S., Matiola, R.T. et al. Coadministration of tianeptine alters behavioral parameters and levels of neurotrophins in a chronic model of Maple Syrup Urine disease. Metab Brain Dis 37, 1585–1596 (2022). https://doi.org/10.1007/s11011-022-00969-8

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