CoChat
Sign Up
Cited by 403Treatment of Major DepressionNerve injury and regenerationTryptophan and brain disorders

Peripheral BDNF Produces Antidepressant-Like Effects in Cellular and Behavioral Models

Open access
Schmidt, Heath D, Duman, Ronald S·2010·Neuropsychopharmacology
DOI 10.1038/npp.2010.114PMC PMC2955759
Open this paper in CoChat — free account

Abstract

Recent clinical studies demonstrate that serum levels of brain-derived neurotrophic factor (BDNF) are significantly decreased in patients with major depressive disorder (MDD) and that antidepressant treatments reverse this effect, indicating that serum BDNF is a biomarker of MDD. These findings raise the possibility that serum BDNF may also have effects on neuronal activity and behavior, but the functional significance of altered serum BDNF is unknown. To address this issue, we determined the influence of peripheral BDNF administration on depression- and anxiety-like behavior, including the forced swim test (FST), chronic unpredictable stress (CUS)/anhedonia, novelty-induced hypophagia (NIH) test, and elevated-plus maze (EPM). Furthermore, we examined adult hippocampal neurogenesis as well as hippocampal and striatal expression of BDNF, extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB), in order to determine whether peripherally administered BDNF produces antidepressant-like cellular responses in the brain. Peripheral BDNF administration increased mobility in the FST, attenuated the effects of CUS on sucrose consumption, decreased latency in the NIH test, and increased time spent in the open arms of an EPM. Moreover, adult hippocampal neurogenesis was increased after chronic, peripheral BDNF administration. We also found that BDNF levels as well as expression of pCREB and pERK were elevated in the hippocampus of adult mice receiving peripheral BDNF. Taken together, these results indicate that peripheral/serum BDNF may not only represent a biomarker of MDD, but also have functional consequences on molecular signaling substrates, neurogenesis, and behavior.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/npp.2010.114

Cites

12 of 12 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Experiments conducted to date support the hypothesis that a global increase in BDNF expression or TrkB activation induces an overall antidepressant effect.

    “Since BDNF-TrkB signaling may contribute differently to the symptomatology of depression depending on brain region (c.f. above), it is not certain that a global increase in BDNF expression or TrkB activation induces an overall antidepressant effect, although experiments conducted to date support this hypothesis (Duman and Voleti, 2012; Schmidt and Duman, 2010).”

    From BDNF - a key transducer of antidepressant effects (2016) · cites this paper as Schmidt and Duman, 2010

    The Introduction (page unavailable) reports that chronic peripheral BDNF administration produced antidepressant-like behavioral responses in animal models and increased BDNF signaling in the hippocampus. The Discussion (page unavailable) says these effects likely involve increased brain BDNF and TrkB-ERK signaling, which supports the hypothesis. The study did not establish a global increase in BDNF expression or TrkB activation across brain regions, so that part of the claim exceeds its findings. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Peripheral, subcutaneous injections of BDNF produce antidepressant- and anxiolytic-like effects in rodents, prevent depression-related effects of chronic stress, and increase cell survival in the hippocampus and prefrontal cortex.

    “In separate work, peripheral, subcutaneous injections of BDNF were reported to produce antidepressant- and anxiolytic-like effects in rodents, prevent depression-related effects of chronic stress, and to increase cell survival in the hippocampus and prefrontal cortex (Schmidt and Duman, 2010).”

    From BDNF - a key transducer of antidepressant effects (2016) · cites this paper as Schmidt and Duman, 2010

    The Results and Discussion report antidepressant- and anxiolytic-like effects in mice and increased survival of cells in the hippocampus and prefrontal cortex. But the Results describe only partial attenuation of chronic-stress-induced anhedonia, not prevention of the stress effects; the Methods specify continuous subcutaneous delivery by implanted pumps rather than injections (page numbers unavailable). (LLM, conf=0.90)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 96

  1. Aberg MA Aberg ND Hedbacker H Oscarsson J Eriksson PS Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus J Neurosci 2000 20 8 2896 2903 10751442 PMC6772218
  2. Altar CA Boylan CB Jackson C Hershenson S Miller J Wiegand SJ Brain-derived neurotrophic factor augments rotational behavior and nigrostriatal dopamine turnover in vivo Proc Natl Acad Sci U S A 1992 89 23 11347 11351 1454818 PMC50547
  3. Aydemir C Yalcin ES Aksaray S Kisa C Yildirim SG Uzbay T Brain-derived neurotrophic factor (BDNF) changes in the serum of depressed women Prog Neuropsychopharmacol Biol Psychiatry 2006 30 7 1256 1260 16647794
  4. Aydemir O Deveci A Taneli F The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study Prog Neuropsychopharmacol Biol Psychiatry 2005 29 2 261 265 15694233
  5. Banasr M Duman RS Glial Loss in the Prefrontal Cortex Is Sufficient to Induce Depressive-like Behaviors Biol Psychiatry 2008 64 10 863 870 18639237 PMC2709733
  6. Banasr M Valentine GW Li XY Gourley SL Taylor JR Duman RS Chronic unpredictable stress decreases cell proliferation in the cerebral cortex of the adult rat Biol Psychiatry 2007b 62 5 496 504 17585885
  7. Berton O McClung CA Dileone RJ Krishnan V Renthal W Russo SJ Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress Science 2006 311 5762 864 868 16469931
  8. Bocchio-Chiavetto L Zanardini R Bortolomasi M Abate M Segala M Giacopuzzi M Electroconvulsive Therapy (ECT) increases serum Brain Derived Neurotrophic Factor (BDNF) in drug resistant depressed patients Eur Neuropsychopharmacol 2006 16 8 620 624 16757154
  9. Branchi I D'Andrea I Sietzema J Fiore M Di Fausto V Aloe L Early social enrichment augments adult hippocampal BDNF levels and survival of BrdU-positive cells while increasing anxiety- and "depression"-like behavior J Neurosci Res 2006 83 6 965 973 16477619
  10. Braun A Lommatzsch M Mannsfeldt A Neuhaus-Steinmetz U Fischer A Schnoy N Cellular sources of enhanced brain-derived neurotrophic factor production in a mouse model of allergic inflammation Am J Respir Cell Mol Biol 1999 21 4 537 546 10502564
  11. Brunoni AR Lopes M Fregni F A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression Int J Neuropsychopharmacol 2008 11 8 1169 1180 18752720
  12. Caldarone BJ Karthigeyan K Harrist A Hunsberger JG Wittmack E King SL Sex differences in response to oral amitriptyline in three animal models of depression in C57BL/6J mice Psychopharmacology (Berl) 2003 170 1 94 101 12879206
  13. Cameron HA Gould E Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus Neuroscience 1994 61 2 203 209 7969902
  14. Carlezon WA Jr Duman RS Nestler EJ The many faces of CREB Trends Neurosci 2005 28 8 436 445 15982754
  15. Chen AC Shirayama Y Shin KH Neve RL Duman RS Expression of the cAMP response element binding protein (CREB) in hippocampus produces an antidepressant effect Biol Psychiatry 2001a 49 9 753 762 11331083
  16. Chen B Dowlatshahi D MacQueen GM Wang JF Young LT Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication Biol Psychiatry 2001b 50 4 260 265 11522260
  17. Chen ZY Jing D Bath KG Ieraci A Khan T Siao CJ Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior Science 2006 314 5796 140 143 17023662 PMC1880880
  18. Cirulli F Berry A Chiarotti F Alleva E Intrahippocampal administration of BDNF in adult rats affects short-term behavioral plasticity in the Morris water maze and performance in the elevated plus-maze Hippocampus 2004 14 7 802 807 15382250
  19. Cotter D Mackay D Chana G Beasley C Landau S Everall IP Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder Cereb Cortex 2002 12 4 386 394 11884354
  20. Cotter D Mackay D Landau S Kerwin R Everall I Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder Arch Gen Psychiatry 2001 58 6 545 553 11386983
  21. Cryan JF Page ME Lucki I Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment Psychopharmacology (Berl) 2005 182 3 335 344 16001105
  22. Czeh B Muller-Keuker JI Rygula R Abumaria N Hiemke C Domenici E Chronic social stress inhibits cell proliferation in the adult medial prefrontal cortex: hemispheric asymmetry and reversal by fluoxetine treatment Neuropsychopharmacology 2007 32 7 1490 1503 17164819
  23. Deltheil T Tanaka K Reperant C Hen R David DJ Gardier AM Synergistic neurochemical and behavioural effects of acute intrahippocampal injection of brain-derived neurotrophic factor and antidepressants in adult mice Int J Neuropsychopharmacol 2009 1 11 19236729
  24. Dulawa SC Hen R Recent advances in animal models of chronic antidepressant effects: the novelty-induced hypophagia test Neurosci Biobehav Rev 2005 29 4–5 771 783 15890403
  25. Dulawa SC Holick KA Gundersen B Hen R Effects of chronic fluoxetine in animal models of anxiety and depression Neuropsychopharmacology 2004 29 7 1321 1330 15085085
  26. Duman CH Schlesinger L Kodama M Russell DS Duman RS A Role for MAP Kinase Signaling in Behavioral Models of Depression and Antidepressant Treatment Biol Psychiatry 2007 61 5 661 670 16945347
  27. Duman CH Schlesinger L Terwilliger R Russell DS Newton SS Duman RS Peripheral insulin-like growth factor-I produces antidepressant-like behavior and contributes to the effect of exercise Behav Brain Res 2008 PMC2729431 19056428
  28. Duman RS Monteggia LM A neurotrophic model for stress-related mood disorders Biol Psychiatry 2006 59 12 1116 1127 16631126
  29. Dwivedi Y Rizavi HS Conley RR Roberts RC Tamminga CA Pandey GN Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects Arch Gen Psychiatry 2003 60 8 804 815 12912764
  30. Egan MF Kojima M Callicott JH Goldberg TE Kolachana BS Bertolino A The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function Cell 2003 112 2 257 269 12553913
  31. Eisch AJ Bolanos CA de Wit J Simonak RD Pudiak CM Barrot M Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: a role in depression Biol Psychiatry 2003 54 10 994 1005 14625141
  32. Fabel K Fabel K Tam B Kaufer D Baiker A Simmons N VEGF is necessary for exercise-induced adult hippocampal neurogenesis Eur J Neurosci 2003 18 10 2803 2812 14656329
  33. Gatt JM Nemeroff CB Dobson-Stone C Paul RH Bryant RA Schofield PR Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety Mol Psychiatry 2009 14 7 681 695 19153574
  34. Gervasoni N Aubry JM Bondolfi G Osiek C Schwald M Bertschy G Partial normalization of serum brain-derived neurotrophic factor in remitted patients after a major depressive episode Neuropsychobiology 2005 51 4 234 238 15897674
  35. Gielen A Khademi M Muhallab S Olsson T Piehl F Increased brain-derived neurotrophic factor expression in white blood cells of relapsing-remitting multiple sclerosis patients Scand J Immunol 2003 57 5 493 497 12753507
  36. Gold PW Chrousos GP Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states Mol Psychiatry 2002 7 3 254 275 11920153
  37. Gorman JM Comorbid depression and anxiety spectrum disorders Depress Anxiety 1996 4 4 160 168 9166648
  38. Gourley SL Kiraly DD Howell JL Olausson P Taylor JR Acute hippocampal brain-derived neurotrophic factor restores motivational and forced swim performance after corticosterone Biol Psychiatry 2008a 64 10 884 890 18675955 PMC2633780
  39. Gourley SL Wu FJ Kiraly DD Ploski JE Kedves AT Duman RS Regionally specific regulation of ERK MAP kinase in a model of antidepressant-sensitive chronic depression Biol Psychiatry 2008b 63 4 353 359 17889834 PMC2277331
  40. Govindarajan A Rao BS Nair D Trinh M Mawjee N Tonegawa S Transgenic brain-derived neurotrophic factor expression causes both anxiogenic and antidepressant effects Proc Natl Acad Sci U S A 2006 103 35 13208 13213 16924103 PMC1559778
  41. Holick KA Lee DC Hen R Dulawa SC Behavioral effects of chronic fluoxetine in BALB/cJ mice do not require adult hippocampal neurogenesis or the serotonin 1A receptor Neuropsychopharmacology 2008 33 2 406 417 17429410
  42. Huang GJ Bannerman D Flint J Chronic fluoxetine treatment alters behavior, but not adult hippocampal neurogenesis, in BALB/cJ mice Mol Psychiatry 2008a 13 2 119 121 18202694
  43. Huang TL Lee CT Liu YL Serum brain-derived neurotrophic factor levels in patients with major depression: effects of antidepressants J Psychiatr Res 2008b 42 7 521 525 17585940
  44. Karege F Bondolfi G Gervasoni N Schwald M Aubry JM Bertschy G Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity Biol Psychiatry 2005a 57 9 1068 1072 15860348
  45. Karege F Vaudan G Schwald M Perroud N La Harpe R Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs Brain Res Mol Brain Res 2005b 136 1–2 29 37 15893584
  46. Kaufman J Charney D Comorbidity of mood and anxiety disorders Depress Anxiety 2000 12 Suppl 1 69 76 11098417
  47. Kawakami T Wakabayashi Y Isono T Aimi Y Okada Y Expression of neurotrophin messenger RNAs during rat urinary bladder development Neurosci Lett 2002 329 1 77 80 12161267
  48. Kerschensteiner M Gallmeier E Behrens L Leal VV Misgeld T Klinkert WE Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med 1999 189 5 865 870 10049950 PMC2192942
  49. Kim YK Lee HP Won SD Park EY Lee HY Lee BH Low plasma BDNF is associated with suicidal behavior in major depression Prog Neuropsychopharmacol Biol Psychiatry 2007 31 1 78 85 16904252
  50. Kodama M Fujioka T Duman RS Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat Biol Psychiatry 2004 56 8 570 580 15476686
  51. Lee BH Kim H Park SH Kim YK Decreased plasma BDNF level in depressive patients J Affect Disord 2006 17173978
  52. Li Y Luikart BW Birnbaum S Chen J Kwon CH Kernie SG TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment Neuron 2008 59 3 399 412 18701066 PMC2655199
  53. Lister RG The use of a plus-maze to measure anxiety in the mouse Psychopharmacology (Berl) 1987 92 2 180 185 3110839
  54. Lommatzsch M Braun A Mannsfeldt A Botchkarev VA Botchkareva NV Paus R Abundant production of brain-derived neurotrophic factor by adult visceral epithelia. Implications for paracrine and target-derived Neurotrophic functions Am J Pathol 1999 155 4 1183 1193 10514401 PMC1867012
  55. Lommatzsch M Niewerth A Klotz J Schulte-Herbruggen O Zingler C Schuff-Werner P Platelet and plasma BDNF in lower respiratory tract infections of the adult Respir Med 2007 101 7 1493 1499 17317133
  56. Lommatzsch M Quarcoo D Schulte-Herbruggen O Weber H Virchow JC Renz H Neurotrophins in murine viscera: a dynamic pattern from birth to adulthood Int J Dev Neurosci 2005 23 6 495 500 15978771
  57. Madsen TM Yeh DD Valentine GW Duman RS Electroconvulsive seizure treatment increases cell proliferation in rat frontal cortex Neuropsychopharmacology 2005 30 1 27 34 15383831
  58. Mufson EJ Kroin JS Liu YT Sobreviela T Penn RD Miller JA Intrastriatal and intraventricular infusion of brain-derived neurotrophic factor in the cynomologous monkey: distribution, retrograde transport and co-localization with substantia nigra dopamine-containing neurons Neuroscience 1996 71 1 179 191 8834401
  59. Mufson EJ Kroin JS Sobreviela T Burke MA Kordower JH Penn RD Intrastriatal infusions of brain-derived neurotrophic factor: retrograde transport and colocalization with dopamine containing substantia nigra neurons in rat Exp Neurol 1994 129 1 15 26 7523178
  60. Nakagawa S Kim JE Lee R Chen J Fujioka T Malberg J Localization of phosphorylated cAMP response element-binding protein in immature neurons of adult hippocampus J Neurosci 2002a 22 22 9868 9876 12427843 PMC6757843
  61. Nakagawa S Kim JE Lee R Malberg JE Chen J Steffen C Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP response element-binding protein J Neurosci 2002b 22 9 3673 3682 11978843 PMC6758358
  62. Nassenstein C Braun A Erpenbeck VJ Lommatzsch M Schmidt S Krug N The neurotrophins nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 are survival and activation factors for eosinophils in patients with allergic bronchial asthma J Exp Med 2003 198 3 455 467 12900521 PMC2194097
  63. Nestler EJ Carlezon WA Jr The mesolimbic dopamine reward circuit in depression Biol Psychiatry 2006 59 12 1151 1159 16566899
  64. Newton SS Thome J Wallace TL Shirayama Y Schlesinger L Sakai N Inhibition of cAMP response element-binding protein or dynorphin in the nucleus accumbens produces an antidepressant-like effect J Neurosci 2002 22 24 10883 10890 12486182 PMC6758459
  65. Okamoto T Yoshimura R Ikenouchi-Sugita A Hori H Umene-Nakano W Inoue Y Efficacy of electroconvulsive therapy is associated with changing blood levels of homovanillic acid and brain-derived neurotrophic factor (BDNF) in refractory depressed patients: a pilot study Prog Neuropsychopharmacol Biol Psychiatry 2008 32 5 1185 1190 18403081
  66. Pardridge WM Wu D Sakane T Combined use of carboxyl-directed protein pegylation and vector-mediated blood-brain barrier drug delivery system optimizes brain uptake of brain-derived neurotrophic factor following intravenous administration Pharm Res 1998 15 4 576 582 9587954
  67. Paxinos G Franklin KB The mouse brain in stereotaxic coordinates 2001 New York Academic Press
  68. Pearse RN Swendeman SL Li Y Rafii D Hempstead BL A neurotrophin axis in myeloma: TrkB and BDNF promote tumor-cell survival Blood 2005 105 11 4429 4436 15657181
  69. Pellow S Chopin P File SE Briley M Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat J Neurosci Methods 1985 14 3 149 167 2864480
  70. Poduslo JF Curran GL Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF Brain Res Mol Brain Res 1996 36 2 280 286 8965648
  71. Price RD Milne SA Sharkey J Matsuoka N Advances in small molecules promoting neurotrophic function Pharmacol Ther 2007 115 2 292 306 17599430
  72. Radka SF Holst PA Fritsche M Altar CA Presence of brain-derived neurotrophic factor in brain and human and rat but not mouse serum detected by a sensitive and specific immunoassay Brain Res 1996 709 1 122 301 8869564
  73. Rajkowska G Miguel-Hidalgo JJ Wei J Dilley G Pittman SD Meltzer HY Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression Biol Psychiatry 1999 45 9 1085 1098 10331101
  74. Saarelainen T Hendolin P Lucas G Koponen E Sairanen M MacDonald E Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects J Neurosci 2003 23 1 349 357 12514234 PMC6742146
  75. Sairanen M Lucas G Ernfors P Castren M Castren E Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus J Neurosci 2005 25 5 1089 1094 15689544 PMC6725966
  76. Santarelli L Saxe M Gross C Surget A Battaglia F Dulawa S Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants Science 2003 301 5634 805 809 12907793
  77. Scarisbrick IA Jones EG Isackson PJ Coexpression of mRNAs for NGF, BDNF, and NT-3 in the cardiovascular system of the pre- and postnatal rat J Neurosci 1993 13 3 875 893 8441013 PMC6576594
  78. Schmidt HD Banasr M Duman RS Future Antidepressant Targets: Neurotrophic Factors and Related Signaling Cascades Drug Discov Today Ther Strateg 2008 5 3 151 156 19802372 PMC2739451
  79. Schmidt HD Duman RS The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior Behav Pharmacol 2007 18 5–6 391 418 17762509
  80. Sen S Duman R Sanacora G Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications Biol Psychiatry 2008 64 6 527 532 18571629 PMC2597158
  81. Shimizu E Hashimoto K Okamura N Koike K Komatsu N Kumakiri C Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants Biol Psychiatry 2003 54 1 70 75 12842310
  82. Shirayama Y Chen AC Nakagawa S Russell DS Duman RS Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression J Neurosci 2002 22 8 3251 3261 11943826 PMC6757539
  83. Siuciak JA Lewis DR Wiegand SJ Lindsay RM Antidepressant-like effect of brain-derived neurotrophic factor (BDNF) Pharmacol Biochem Behav 1997 56 1 131 137 8981620
  84. Timmusk T Palm K Metsis M Reintam T Paalme V Saarma M Multiple promoters direct tissue-specific expression of the rat BDNF gene Neuron 1993 10 3 475 489 8461137
  85. Uranova NA Vostrikov VM Orlovskaya DD Rachmanova VI Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium Schizophr Res 2004 67 2–3 269 275 14984887
  86. Wallace DL Han MH Graham DL Green TA Vialou V Iniguez SD CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits Nat Neurosci 2009 12 2 200 209 19151710 PMC2721778
  87. Wang JW David DJ Monckton JE Battaglia F Hen R Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells J Neurosci 2008 28 6 1374 1384 18256257 PMC6671574
  88. Warner-Schmidt JL Duman RS VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants Proc Natl Acad Sci U S A 2007 104 11 4647 4652 17360578 PMC1838655
  89. Willner P Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation Psychopharmacology (Berl) 1997 134 4 319 329 9452163
  90. Willner P Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS Neuropsychobiology 2005 52 2 90 110 16037678
  91. Willner P Moreau JL Nielsen CK Papp M Sluzewska A Decreased hedonic responsiveness following chronic mild stress is not secondary to loss of body weight Physiol Behav 1996 60 1 129 134 8804652
  92. Yalcin I Belzung C Surget A Mouse strain differences in the unpredictable chronic mild stress: a four-antidepressant survey Behav Brain Res 2008 193 1 140 143 18565601
  93. Yamamoto M Sobue G Yamamoto K Terao S Mitsuma T Expression of mRNAs for neurotrophic factors (NGF, BDNF, NT-3, and GDNF) and their receptors (p75NGFR, trkA, trkB, and trkC) in the adult human peripheral nervous system and nonneural tissues Neurochem Res 1996 21 8 929 938 8895847
  94. Yoshimura R Mitoma M Sugita A Hori H Okamoto T Umene W Effects of paroxetine or milnacipran on serum brain-derived neurotrophic factor in depressed patients Prog Neuropsychopharmacol Biol Psychiatry 2007 31 5 1034 1037 17459550
  95. Zanardini R Gazzoli A Ventriglia M Perez J Bignotti S Rossini PM Effect of repetitive transcranial magnetic stimulation on serum brain derived neurotrophic factor in drug resistant depressed patients J Affect Disord 2006 91 1 83 86 16448701
  96. Zhang Y Pardridge WM Conjugation of brain-derived neurotrophic factor to a blood-brain barrier drug targeting system enables neuroprotection in regional brain ischemia following intravenous injection of the neurotrophin Brain Res 2001 889 1–2 49 56 11166685

Cited by

Sorted by citations

Authors
Schmidt, H. D., & Duman, R. S.
Affiliations
Yale University (US)
Corresponding author
Duman, Ronald S
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2010-08-04
Volume
35
Issue
12
Pages
2378-2391
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/npp.2010.114
PMC
PMC2955759
OpenAlex
W2072457730
Cited by
403
References
12
Citations by year
2026: 3 · 2025: 11 · 2024: 20 · 2023: 18 · 2022: 25 · 2021: 14 · 2020: 18 · 2019: 24 · 2018: 23 · 2017: 32 · 2016: 28 · 2015: 31 · 2014: 40 · 2013: 43 · 2012: 40
FWCI
27.13
Type
journal article
Language
en
Update notices
erratum (2010-11-17)
Open access
Licence
Locations
  • Neuropsychopharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Regeneron Pharmaceuticals
  • National Institutes of Health
  • U.S. Public Health Service
  • National Institute of Mental Health (2P01 MH25642, MH-45481, R37MH045481, P01MH025642, R01MH045481)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
brain-derived neurotrophic factor, major depressive disorder, antidepressant-like effects, depression-like behavior, anxiety-like behavior, anhedonia, novelty-induced hypophagia, adult hippocampal neurogenesis, CREB phosphorylation, ERK1/2 phosphorylation, chronic unpredictable mild stress, serum biomarkers
MeSH terms
Animals, Antidepressive Agents, Anxiety, Corpus Striatum, Depression, Disease Models, Animal, Hippocampus, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Recombinant Proteins, Anti-Anxiety Agents, Cyclic AMP Response Element-Binding Protein, Brain-Derived Neurotrophic Factor, Extracellular Signal-Regulated MAP Kinases, Mice, Infusions, Subcutaneous, Neurogenesis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review