Interaction of Brain-derived Neurotrophic Factor, Exercise, and Fear Extinction: Implications for Post-traumatic Stress Disorder


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Abstract

Brain-Derived Neurotrophic Factor (BDNF) plays an important role in brain development, neural plasticity, and learning and memory. The Val66Met single-nucleotide polymorphism is a common genetic variant that results in deficient activity-dependent release of BDNF. This polymorphism and its impact on fear conditioning and extinction, as well as on symptoms of post-traumatic stress disorder (PTSD), have been of increasing research interest over the last two decades. More recently, it has been demonstrated that regular physical activity may ameliorate impairments in fear extinction and alleviate symptoms in individuals with PTSD via an action on BDNF levels and that there are differential responses to exercise between the Val66Met genotypes. This narrative literature review first describes the theoretical underpinnings of the development and persistence of intrusive and hypervigilance symptoms commonly seen in PTSD and their treatment. It then discusses recent literature on the involvement of BDNF and the Val66Met polymorphism in fear conditioning and extinction and its involvement in PTSD diagnosis and severity. Finally, it investigates research on the impact of physical activity on BDNF secretion, the differences between the Val66Met genotypes, and the effect on fear extinction learning and memory and symptoms of PTSD.

About the authors

Emily Antolasic

School of Psychology and Public Health, La Trobe University

Email: info@benthamscience.net

Emily Jaehne

School of Psychology and Public Health, La Trobe University

Email: info@benthamscience.net

Maarten van den Buuse

School of Psychology and Public Health, La Trobe University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Koenen, K.C.; Ratanatharathorn, A.; Ng, L.; McLaughlin, K.A.; Bromet, E.J.; Stein, D.J.; Karam, E.G.; Meron Ruscio, A.; Benjet, C.; Scott, K.; Atwoli, L.; Petukhova, M.; Lim, C.C.W.; Aguilar-Gaxiola, S.; Al-Hamzawi, A.; Alonso, J.; Bunting, B.; Ciutan, M.; de Girolamo, G.; Degenhardt, L.; Gureje, O.; Haro, J.M.; Huang, Y.; Kawakami, N.; Lee, S.; Navarro-Mateu, F.; Pennell, B.E.; Piazza, M.; Sampson, N.; ten Have, M.; Torres, Y.; Viana, M.C.; Williams, D.; Xavier, M.; Kessler, R.C. Posttraumatic stress disorder in the world mental health surveys. Psychol. Med., 2017, 47(13), 2260-2274. doi: 10.1017/S0033291717000708 PMID: 28385165
  2. Lewis, S.J.; Arseneault, L.; Caspi, A.; Fisher, H.L.; Matthews, T.; Moffitt, T.E.; Odgers, C.L.; Stahl, D.; Teng, J.Y.; Danese, A. The epidemiology of trauma and post-traumatic stress disorder in a representative cohort of young people in England and Wales. Lancet Psychiatry, 2019, 6(3), 247-256. doi: 10.1016/S2215-0366(19)30031-8 PMID: 30798897
  3. Salehi, M.; Amanat, M.; Mohammadi, M.; Salmanian, M.; Rezaei, N.; Saghazadeh, A.; Garakani, A. The prevalence of post-traumatic stress disorder related symptoms in Coronavirus outbreaks: A systematic-review and meta-analysis. J. Affect. Disord., 2021, 282, 527-538. doi: 10.1016/j.jad.2020.12.188 PMID: 33433382
  4. Woolgar, F.; Garfield, H.; Dalgleish, T.; Meiser-Stedman, R. Systematic review and meta-analysis: prevalence of posttraumatic stress disorder in trauma-exposed preschool-aged children. J. Am. Acad. Child Adolesc. Psychiatry, 2022, 61(3), 366-377.
  5. Olff, M. Sex and gender differences in post-traumatic stress disorder: An update. Eur. J. Psychotraumatol., 2017, 8(sup4), 1351204. doi: 10.1080/20008198.2017.1351204
  6. Diagnostic and statistical manual of mental disorders (DSM-5), 5th ed; American Psychiatric Association: Arlington, VA, 2013.
  7. Hayes, J.P.; LaBar, K.S.; McCarthy, G.; Selgrade, E.; Nasser, J.; Dolcos, F.; Morey, R.A. Reduced hippocampal and amygdala activity predicts memory distortions for trauma reminders in combat-related PTSD. J. Psychiatr. Res., 2011, 45(5), 660-669.
  8. Li, H.; Penzo, M.A.; Taniguchi, H.; Kopec, C.D.; Huang, Z.J.; Li, B. Experience-dependent modification of a central amygdala fear circuit. Nat. Neurosci., 2013, 16(3), 332-339. doi: 10.1038/nn.3322 PMID: 23354330
  9. Nievergelt, C.M.; Maihofer, A.X.; Klengel, T.; Atkinson, E.G.; Chen, C.Y.; Choi, K.W.; Coleman, J.R.I.; Dalvie, S.; Duncan, L.E.; Gelernter, J.; Levey, D.F.; Logue, M.W.; Polimanti, R.; Provost, A.C.; Ratanatharathorn, A.; Stein, M.B.; Torres, K.; Aiello, A.E.; Almli, L.M.; Amstadter, A.B.; Andersen, S.B.; Andreassen, O.A.; Arbisi, P.A.; Ashley-Koch, A.E.; Austin, S.B.; Avdibegovic, E.; Babić, D.; Bækvad-Hansen, M.; Baker, D.G.; Beckham, J.C.; Bierut, L.J.; Bisson, J.I.; Boks, M.P.; Bolger, E.A.; Børglum, A.D.; Bradley, B.; Brashear, M.; Breen, G.; Bryant, R.A.; Bustamante, A.C.; Bybjerg-Grauholm, J.; Calabrese, J.R. Caldas- de- Almeida, J.M.; Dale, A.M.; Daly, M.J.; Daskalakis, N.P.; Deckert, J.; Delahanty, D.L.; Dennis, M.F.; Disner, S.G.; Domschke, K.; Dzubur-Kulenovic, A.; Erbes, C.R.; Evans, A.; Farrer, L.A.; Feeny, N.C.; Flory, J.D.; Forbes, D.; Franz, C.E.; Galea, S.; Garrett, M.E.; Gelaye, B.; Geuze, E.; Gillespie, C.; Uka, A.G.; Gordon, S.D.; Guffanti, G.; Hammamieh, R.; Harnal, S.; Hauser, M.A.; Heath, A.C.; Hemmings, S.M.J.; Hougaard, D.M.; Jakovljevic, M.; Jett, M.; Johnson, E.O.; Jones, I.; Jovanovic, T.; Qin, X.J.; Junglen, A.G.; Karstoft, K.I.; Kaufman, M.L.; Kessler, R.C.; Khan, A.; Kimbrel, N.A.; King, A.P.; Koen, N.; Kranzler, H.R.; Kremen, W.S.; Lawford, B.R.; Lebois, L.A.M.; Lewis, C.E.; Linnstaedt, S.D.; Lori, A.; Lugonja, B.; Luykx, J.J.; Lyons, M.J.; Maples-Keller, J.; Marmar, C.; Martin, A.R.; Martin, N.G.; Maurer, D.; Mavissakalian, M.R.; McFarlane, A.; McGlinchey, R.E.; McLaughlin, K.A.; McLean, S.A.; McLeay, S.; Mehta, D.; Milberg, W.P.; Miller, M.W.; Morey, R.A.; Morris, C.P.; Mors, O.; Mortensen, P.B.; Neale, B.M.; Nelson, E.C.; Nordentoft, M.; Norman, S.B.; O’Donnell, M.; Orcutt, H.K.; Panizzon, M.S.; Peters, E.S.; Peterson, A.L.; Peverill, M.; Pietrzak, R.H.; Polusny, M.A.; Rice, J.P.; Ripke, S.; Risbrough, V.B.; Roberts, A.L.; Rothbaum, A.O.; Rothbaum, B.O.; Roy-Byrne, P.; Ruggiero, K.; Rung, A.; Rutten, B.P.F.; Saccone, N.L.; Sanchez, S.E.; Schijven, D.; Seedat, S.; Seligowski, A.V.; Seng, J.S.; Sheerin, C.M.; Silove, D.; Smith, A.K.; Smoller, J.W.; Sponheim, S.R.; Stein, D.J.; Stevens, J.S.; Sumner, J.A.; Teicher, M.H.; Thompson, W.K.; Trapido, E.; Uddin, M.; Ursano, R.J.; van den Heuvel, L.L.; Van Hooff, M.; Vermetten, E.; Vinkers, C.H.; Voisey, J.; Wang, Y.; Wang, Z.; Werge, T.; Williams, M.A.; Williamson, D.E.; Winternitz, S.; Wolf, C.; Wolf, E.J.; Wolff, J.D.; Yehuda, R.; Young, R.M.; Young, K.A.; Zhao, H.; Zoellner, L.A.; Liberzon, I.; Ressler, K.J.; Haas, M.; Koenen, K.C. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci. Nat. Commun., 2019, 10(1), 4558. doi: 10.1038/s41467-019-12576-w PMID: 31594949
  10. Friedman, M.J.; Keane, T.M.; Resick, P.A.; Amaya-Jackson, L.M. Handbook of PTSD: Science and practice, 2nd ed; Guilford Press: New York, 2014.
  11. Lancaster, C.; Teeters, J.; Gros, D.; Back, S. Posttraumatic Stress Disorder: Overview of evidence-based assessment and treatment. J. Clin. Med., 2016, 5(11), 105. doi: 10.3390/jcm5110105 PMID: 27879650
  12. Flandreau, E.I.; Toth, M. Animal models of PTSD: A critical review. Curr. Top. Behav. Neurosci., 2017, 38, 47-68. doi: 10.1007/7854_2016_65 PMID: 28070873
  13. Milad, M.R.; Rauch, S.L.; Pitman, R.K.; Quirk, G.J. Fear extinction in rats: Implications for human brain imaging and anxiety disorders. Biol. Psychol., 2006, 73(1), 61-71. doi: 10.1016/j.biopsycho.2006.01.008 PMID: 16476517
  14. Fanselow, M.S. What is conditioned fear? Trends Neurosci., 1984, 7(12), 460-462. doi: 10.1016/S0166-2236(84)80253-2
  15. Milad, M.R.; Quirk, G.J. Fear extinction as a model for translational neuroscience: Ten years of progress. Annu. Rev. Psychol., 2012, 63, 129-151. doi: 10.1146/annurev.psych.121208.131631
  16. Andero, R.; Ressler, K.J. Fear extinction and BDNF: Translating animal models of PTSD to the clinic. Genes Brain Behav., 2012, 11(5), 503-512. doi: 10.1111/j.1601-183X.2012.00801.x PMID: 22530815
  17. Kim, J.J.; Jung, M.W. Neural circuits and mechanisms involved in Pavlovian fear conditioning: A critical review. Neurosci. Biobehav. Rev., 2006, 30(2), 188-202. doi: 10.1016/j.neubiorev.2005.06.005 PMID: 16120461
  18. Milad, M.R.; Quirk, G.J. Neurons in medial prefrontal cortex signal memory for fear extinction. Nature, 2002, 420(6911), 70-74. doi: 10.1038/nature01138 PMID: 12422216
  19. Ravindran, L.N.; Stein, M.B. Pharmacotherapy of PTSD: Premises, principles, and priorities. Brain Res., 2009, 1293, 24-39. doi: 10.1016/j.brainres.2009.03.037 PMID: 19332035
  20. Asnis, G.M.; Kohn, S.R.; Henderson, M.; Brown, N.L. SSRIs versus non-SSRIs in post-traumatic stress disorder: An update with recommendations. Drugs, 2004, 64(4), 383-404. doi: 10.2165/00003495-200464040-00004 PMID: 14969574
  21. Huang, E.J.; Reichardt, L.F. Neurotrophins: Roles in neuronal development and function. Ann. Rev. Neurosci., 2001, 24(1), 677-736.
  22. Notaras, M.; van den Buuse, M. Brain-derived neurotrophic factor and its role in stress-related disorders. Stress: Genetics, epigenetics, and genomics; Fink, G., Ed.; Academic Press, Elsevier: San Diego, Cambridge, Oxford, 2021, Vol. 4, pp. 253-261. doi: 10.1016/B978-0-12-813156-5.00023-6
  23. Notaras, M.; Hill, R.; van den Buuse, M. The BDNF gene Val66Met polymorphism as a modifier of psychiatric disorder susceptibility: progress and controversy. Mol. Psychiatry, 2015, 20(8), 916-930. doi: 10.1038/mp.2015.27 PMID: 25824305
  24. Notaras, M.; van den Buuse, M. Brain-Derived Neurotrophic Factor (BDNF): Novel insights into regulation and genetic variation. Neuroscientist, 2019, 25(5), 434-454. doi: 10.1177/1073858418810142 PMID: 30387693
  25. Yang, J.; Siao, C.J.; Nagappan, G.; Marinic, T.; Jing, D.; McGrath, K.; Chen, Z.Y.; Mark, W.; Tessarollo, L.; Lee, F.S.; Lu, B.; Hempstead, B.L. Neuronal release of proBDNF. Nat. Neurosci., 2009, 12(2), 113-115. doi: 10.1038/nn.2244 PMID: 19136973
  26. Nagappan, G.; Zaitsev, E.; Senatorov, V.V., Jr; Yang, J.; Hempstead, B.L.; Lu, B. Control of extracellular cleavage of ProBDNF by high frequency neuronal activity. Proc. Natl. Acad. Sci. USA, 2009, 106(4), 1267-1272. doi: 10.1073/pnas.0807322106 PMID: 19147841
  27. Notaras, M.; van den Buuse, M. Neurobiology of BDNF in fear memory, sensitivity to stress, and stress-related disorders. Mol. Psychiatry, 2020, 25(10), 2251-2274. doi: 10.1038/s41380-019-0639-2 PMID: 31900428
  28. Conner, J.M.; Lauterborn, J.C.; Yan, Q.; Gall, C.M.; Varon, S. Distribution of brain-derived neurotrophic factor (BDNF) protein and mRNA in the normal adult rat CNS: evidence for anterograde axonal transport. J. Neurosci., 1997, 17(7), 2295-2313. doi: 10.1523/JNEUROSCI.17-07-02295.1997 PMID: 9065491
  29. Minichiello, L. TrkB signalling pathways in LTP and learning. Nat. Rev. Neurosci., 2009, 10(12), 850-860. doi: 10.1038/nrn2738 PMID: 19927149
  30. Miranda, M.; Morici, J.F.; Zanoni, M.B.; Bekinschtein, P. Brain-Derived Neurotrophic Factor: A key molecule for memory in the healthy and the pathological brain. Front. Cell. Neurosci., 2019, 13, 363. doi: 10.3389/fncel.2019.00363
  31. Figurov, A.; Pozzo-Miller, L.D.; Olafsson, P.; Wang, T.; Lu, B. Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Nature, 1996, 381(6584), 706-709. doi: 10.1038/381706a0 PMID: 8649517
  32. Sasi, M.; Vignoli, B.; Canossa, M.; Blum, R. Neurobiology of local and intercellular BDNF signaling. Pflugers Arch., 2017, 469(5-6), 593-610. doi: 10.1007/s00424-017-1964-4 PMID: 28280960
  33. Hill, R.A.; van den Buuse, M. Sex-dependent and region-specific changes in TrkB signaling in BDNF heterozygous mice. Brain Res., 2011, 1384, 51-60. doi: 10.1016/j.brainres.2011.01.060
  34. Klug, M.; Hill, R.A.; Choy, K.H.C.; Kyrios, M.; Hannan, A.J.; van den Buuse, M. Long-term behavioral and NMDA receptor effects of young-adult corticosterone treatment in BDNF heterozygous mice. Neurobiol. Dis., 2012, 46(3), 722-731. doi: 10.1016/j.nbd.2012.03.015 PMID: 22426399
  35. Montkowski, A.; Holsboer, F. Intact spatial learning and memory in transgenic mice with reduced BDNF. Neuroreport, 1997, 8(3), 779-782. doi: 10.1097/00001756-199702100-00040 PMID: 9106766
  36. Gray, J.; Yeo, G.S.H.; Cox, J.J.; Morton, J.; Adlam, A.L.R.; Keogh, J.M.; Yanovski, J.A.; El Gharbawy, A.; Han, J.C.; Tung, Y.C.L.; Hodges, J.R.; Raymond, F.L.; O’Rahilly, S.; Farooqi, I.S. Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene. Diabetes, 2006, 55(12), 3366-3371. doi: 10.2337/db06-0550 PMID: 17130481
  37. Gray, J.; Yeo, G.; Hung, C.; Keogh, J.; Clayton, P.; Banerjee, K.; McAulay, A.; O’Rahilly, S.; Farooqi, I.S. Functional characterization of human NTRK2 mutations identified in patients with severe early-onset obesity. Int. J. Obes., 2007, 31(2), 359-364. doi: 10.1038/sj.ijo.0803390
  38. Yeo, G.S.H.; Connie Hung, C.C.; Rochford, J.; Keogh, J.; Gray, J.; Sivaramakrishnan, S.; O’Rahilly, S.; Farooqi, I.S. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat. Neurosci., 2004, 7(11), 1187-1189. doi: 10.1038/nn1336 PMID: 15494731
  39. Arosio, B.; Guerini, F.R.; Voshaar, R.C.O.; Aprahamian, I. Blood Brain-Derived Neurotrophic Factor (BDNF) and Major Depression: Do we have a translational perspective? Front. Behav. Neurosci., 2021, 15, 626906. doi: 10.3389/fnbeh.2021.626906 PMID: 33643008
  40. Arumugam, V.; John, V.; Augustine, N.; Jacob, T.; Joy, S.; Sen, S.; Sen, T. The impact of antidepressant treatment on brain-derived neurotrophic factor level: An evidence-based approach through systematic review and meta-analysis. Indian J. Pharmacol., 2017, 49(3), 236-242. doi: 10.4103/ijp.IJP_700_16 PMID: 29033483
  41. Casarotto, P.C.; Girych, M.; Fred, S.M.; Kovaleva, V.; Moliner, R.; Enkavi, G.; Biojone, C.; Cannarozzo, C.; Sahu, M.P.; Kaurinkoski, K.; Brunello, C.A.; Steinzeig, A.; Winkel, F.; Patil, S.; Vestring, S.; Serchov, T.; Diniz, C.R.A.F.; Laukkanen, L.; Cardon, I.; Antila, H.; Rog, T.; Piepponen, T.P.; Bramham, C.R.; Normann, C.; Lauri, S.E.; Saarma, M.; Vattulainen, I.; Castrén, E. Antidepressant drugs act by directly binding to TRKB neurotrophin receptors. Cell, 2021, 184(5), 1299-1313.e19. doi: 10.1016/j.cell.2021.01.034 PMID: 33606976
  42. Rosas-Vidal, L.E.; Do-Monte, F.H.; Sotres-Bayon, F.; Quirk, G.J. Hippocampal--prefrontal BDNF and memory for fear extinction. Neuropsychopharmacology, 2014, 39(9), 2161-2169. doi: 10.1038/npp.2014.64 PMID: 24625752
  43. Kataoka, T.; Fuchikami, M.; Nojima, S.; Nagashima, N.; Araki, M.; Omura, J.; Miyagi, T.; Okamoto, Y.; Morinobu, S. Combined brain-derived neurotrophic factor with extinction training alleviate impaired fear extinction in an animal model of post-traumatic stress disorder. Genes Brain Behav., 2018, 12520. doi: 10.1111/gbb.12520 PMID: 30246290
  44. Chaaya, N.; Wang, J.; Jacques, A.; Beecher, K.; Chaaya, M.; Battle, A.R.; Johnson, L.R.; Chehrehasa, F.; Belmer, A.; Bartlett, S.E. Contextual fear memory maintenance changes expression of pMAPK, BDNF and IBA-1 in the prelimbic cortex in a layer-specific manner. Front. Neural Circuits, 2021, 15, 660199. doi: 10.3389/fncir.2021.660199 PMID: 34295224
  45. Peters, J.; Dieppa-Perea, L.M.; Melendez, L.M.; Quirk, G.J. Induction of fear extinction with hippocampal-infralimbic BDNF. Science, 2010, 328(5983), 1288-1290. doi: 10.1126/science.1186909 PMID: 20522777
  46. Chang, S.H.; Yu, Y.H.; He, A.; Ou, C.Y.; Shyu, B.C.; Huang, A.C.W. BDNF protein and BDNF mRNA expression of the medial prefrontal cortex, amygdala, and hippocampus during situational reminder in the PTSD animal model. Behav. Neurol., 2021, 2021, 1-13. doi: 10.1155/2021/6657716 PMID: 33763156
  47. Kirtley, A.; Thomas, K.L. The exclusive induction of extinction is gated by BDNF. Learn. Mem., 2010, 17(12), 612-619. doi: 10.1101/lm.1877010 PMID: 21127000
  48. Radiske, A.; Rossato, J.I.; Köhler, C.A.; Gonzalez, M.C.; Medina, J.H.; Cammarota, M. Requirement for BDNF in the reconsolidation of fear extinction. J. Neurosci., 2015, 35(16), 6570-6574. doi: 10.1523/JNEUROSCI.4093-14.2015 PMID: 25904806
  49. Chaaya, N.; Jacques, A.; Belmer, A.; Beecher, K.; Ali, S.A.; Chehrehasa, F.; Battle, A.R.; Johnson, L.R.; Bartlett, S.E. Contextual fear conditioning alter microglia number and morphology in the rat dorsal hippocampus. Front. Cell. Neurosci., 2019, 13, 214. doi: 10.3389/fncel.2019.00214 PMID: 31139053
  50. Endres, T.; Lessmann, V. Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice. Learn. Mem., 2012, 19(12), 561-570. doi: 10.1101/lm.028068.112 PMID: 23154927
  51. Meis, S.; Endres, T.; Munsch, T.; Lessmann, V. The relation between long-term synaptic plasticity at glutamatergic synapses in the amygdala and fear learning in adult heterozygous BDNF-knockout Mice. Cereb. Cortex, 2018, 28(4), 1195-1208. doi: 10.1093/cercor/bhx032 PMID: 28184413
  52. Psotta, L.; Lessmann, V.; Endres, T. Impaired fear extinction learning in adult heterozygous BDNF knock-out mice. Neurobiol. Learn. Mem., 2013, 103, 34-38. doi: 10.1016/j.nlm.2013.03.003 PMID: 23578839
  53. Hill, J.L.; Hardy, N.F.; Jimenez, D.V.; Maynard, K.R.; Kardian, A.S.; Pollock, C.J.; Schloesser, R.J.; Martinowich, K. Loss of promoter IV-driven BDNF expression impacts oscillatory activity during sleep, sensory information processing and fear regulation. Transl. Psychiatry, 2016, 6(8), e873. doi: 10.1038/tp.2016.153 PMID: 27552586
  54. Choi, D.C.; Maguschak, K.A.; Ye, K.; Jang, S.W.; Myers, K.M.; Ressler, K.J. Prelimbic cortical BDNF is required for memory of learned fear but not extinction or innate fear. Proc. Natl. Acad. Sci. USA, 2010, 107(6), 2675-2680. doi: 10.1073/pnas.0909359107 PMID: 20133801
  55. McEwen, B.S.; Bowles, N.P.; Gray, J.D.; Hill, M.N.; Hunter, R.G.; Karatsoreos, I.N.; Nasca, C. Mechanisms of stress in the brain. Nat. Neurosci., 2015, 18(10), 1353-1363. doi: 10.1038/nn.4086 PMID: 26404710
  56. Gururajan, A.; Hill, R.A.; van den Buuse, M. Brain-derived neurotrophic factor heterozygous mutant rats show selective cognitive changes and vulnerability to chronic corticosterone treatment. Neuroscience, 2015, 284, 297-310. doi: 10.1016/j.neuroscience.2014.10.009 PMID: 25445195
  57. Wu, Y.C.; Hill, R.A.; Gogos, A.; van den Buuse, M. Sex differences and the role of estrogen in animal models of schizophrenia: Interaction with BDNF. Neuroscience, 2013, 239, 67-83. doi: 10.1016/j.neuroscience.2012.10.024 PMID: 23085218
  58. Baker-Andresen, D.; Flavell, C.R.; Li, X.; Bredy, T.W. Activation of BDNF signaling prevents the return of fear in female mice. Learn. Mem., 2013, 20(5), 237-240. doi: 10.1101/lm.029520.112 PMID: 23589089
  59. Aksu, S.; Unlu, G.; Kardesler, A.C.; Cakaloz, B.; Aybek, H. Altered levels of brain-derived neurotrophic factor, proBDNF and tissue plasminogen activator in children with posttraumatic stress disorder. Psychiatry Res., 2018, 268, 478-483. doi: 10.1016/j.psychres.2018.07.013 PMID: 30142554
  60. Stratta, P.; Sanità, P.; Bonanni, R.L.; de Cataldo, S.; Angelucci, A.; Rossi, R.; Origlia, N.; Domenici, L.; Carmassi, C.; Piccinni, A.; Dell’Osso, L.; Rossi, A. Clinical correlates of plasma brain-derived neurotrophic factor in post-traumatic stress disorder spectrum after a natural disaster. Psychiatry Res., 2016, 244, 165-170. doi: 10.1016/j.psychres.2016.07.019 PMID: 27479108
  61. Bücker, J.; Fries, G.R.; Kapczinski, F.; Post, R.M.; Yatham, L.N.; Vianna, P.; Bogo Chies, J.A.; Gama, C.S.; Magalhães, P.V.; Aguiar, B.W.; Pfaffenseller, B. Kauer-Sant’Anna, M. Brain-derived neurotrophic factor and inflammatory markers in school-aged children with early trauma. Acta Psychiatr. Scand., 2015, 131(5), 360-368. doi: 10.1111/acps.12358 PMID: 25401224
  62. Matsuoka, Y.; Nishi, D.; Noguchi, H.; Kim, Y.; Hashimoto, K. Longitudinal changes in serum brain-derived neurotrophic factor in accident survivors with posttraumatic stress disorder. Neuropsychobiology, 2013, 68(1), 44-50. doi: 10.1159/000350950 PMID: 23774996
  63. Su, S.; Xiao, Z.; Lin, Z.; Qiu, Y.; Jin, Y.; Wang, Z. Plasma brain-derived neurotrophic factor levels in patients suffering from post-traumatic stress disorder. Psychiatry Res., 2015, 229(1-2), 365-369. doi: 10.1016/j.psychres.2015.06.038 PMID: 26160204
  64. Howie, H.; Rijal, C.M.; Ressler, K.J. A review of epigenetic contributions to post-traumatic stress disorder. Dialogues Clin. Neurosci., 2019, 21(4), 417-428. doi: 10.31887/DCNS.2019.21.4/kressler PMID: 31949409
  65. Kim, T.Y.; Kim, S.J.; Chung, H.G.; Choi, J.H.; Kim, S.H.; Kang, J.I. Epigenetic alterations of the BDNF gene in combat-related post-traumatic stress disorder. Acta Psychiatr. Scand., 2017, 135(2), 170-179. doi: 10.1111/acps.12675 PMID: 27886370
  66. Pilakka-Kanthikeel, S.; Atluri, V.S.; Sagar, V.; Saxena, S.K.; Nair, M. Targeted brain derived neurotropic factors (BDNF) delivery across the blood-brain barrier for neuro-protection using magnetic nano carriers: an in-vitro study. PLoS One, 2013, 8(4), e62241.
  67. Mahan, A.L.; Ressler, K.J. Fear conditioning, synaptic plasticity and the amygdala: implications for posttraumatic stress disorder. Trends Neurosci., 2012, 35(1), 24-35. doi: 10.1016/j.tins.2011.06.007 PMID: 21798604
  68. Zeng, Y.; Liu, Y.; Wu, M.; Liu, J.; Hu, Q. Activation of TrkB by 7,8-dihydroxyflavone prevents fear memory defects and facilitates amygdalar synaptic plasticity in aging. J. Alzheimers Dis., 2012, 31(4), 765-778. doi: 10.3233/JAD-2012-120886 PMID: 22710915
  69. Andero, R.; Heldt, S.A.; Ye, K.; Liu, X.; Armario, A.; Ressler, K.J. Effect of 7,8-dihydroxyflavone, a small-molecule TrkB agonist, on emotional learning. Am. J. Psychiatry, 2011, 168(2), 163-172.
  70. Flavell, C.R.; Lambert, E.A.; Winters, B.D.; Bredy, T.W. Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction. Front. Behav. Neurosci., 2013, 7, 214. doi: 10.3389/fnbeh.2013.00214 PMID: 24421762
  71. Klein, R.; Nanduri, V.; Jing, S.; Lamballe, F.; Tapley, P.; Bryant, S.; Cordon-Cardo, C.; Jones, K.R.; Reichardt, L.F.; Barbacid, M. The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Cell, 1991, 66(2), 395-403. doi: 10.1016/0092-8674(91)90628-C PMID: 1649702
  72. Soppet, D.; Escandon, E.; Maragos, J.; Middlemas, D.S.; Raid, S.W.; Blair, J.; Burton, L.E.; Stanton, B.R.; Kaplan, D.R.; Hunter, T.; Nikolics, K.; Parade, L.F. The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Cell, 1991, 65(5), 895-903. doi: 10.1016/0092-8674(91)90396-G PMID: 1645620
  73. Chen, Z.Y.; Ieraci, A.; Teng, H.; Dall, H.; Meng, C.X.; Herrera, D.G.; Nykjaer, A.; Hempstead, B.L.; Lee, F.S. Sortilin controls intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathway. J. Neurosci., 2005, 25(26), 6156-6166. doi: 10.1523/JNEUROSCI.1017-05.2005 PMID: 15987945
  74. Yang, M.; Lim, Y.; Li, X.; Zhong, J.H.; Zhou, X.F. Precursor of brain-derived neurotrophic factor (proBDNF) forms a complex with Huntingtin-associated protein-1 (HAP1) and sortilin that modulates proBDNF trafficking, degradation, and processing. J. Biol. Chem., 2011, 286(18), 16272-16284. doi: 10.1074/jbc.M110.195347 PMID: 21357693
  75. Chen, Z.Y.; Jing, D.; Bath, K.G.; Ieraci, A.; Khan, T.; Siao, C.J.; Herrera, D.G.; Toth, M.; Yang, C.; McEwen, B.S.; Hempstead, B.L.; Lee, F.S. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science, 2006, 314(5796), 140-143. doi: 10.1126/science.1129663 PMID: 17023662
  76. Mercado, N.M.; Stancati, J.A.; Sortwell, C.E.; Mueller, R.L.; Boezwinkle, S.A.; Duffy, M.F.; Fischer, D.L.; Sandoval, I.M.; Manfredsson, F.P.; Collier, T.J.; Steece-Collier, K. The BDNF Val66Met polymorphism (rs6265) enhances dopamine neuron graft efficacy and side-effect liability in rs6265 knock-in rats. Neurobiol. Dis., 2021, 148, 105175. doi: 10.1016/j.nbd.2020.105175 PMID: 33188920
  77. Egan, M.F.; Kojima, M.; Callicott, J.H.; Goldberg, T.E.; Kolachana, B.S.; Bertolino, A.; Zaitsev, E.; Gold, B.; Goldman, D.; Dean, M.; Lu, B.; Weinberger, D.R. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell, 2003, 112(2), 257-269. doi: 10.1016/S0092-8674(03)00035-7 PMID: 12553913
  78. Petryshen, T.L.; Sabeti, P.C.; Aldinger, K.A.; Fry, B.; Fan, J.B.; Schaffner, S.F.; Waggoner, S.G.; Tahl, A.R.; Sklar, P. Population genetic study of the brain-derived neurotrophic factor (BDNF) gene. Mol. Psychiatry, 2010, 15(8), 810-815. doi: 10.1038/mp.2009.24 PMID: 19255578
  79. Dincheva, I.; Pattwell, S.S.; Tessarollo, L.; Bath, K.G.; Lee, F.S. BDNF modulates contextual fear learning during adolescence. Dev. Neurosci., 2014, 36(3-4), 269-276. doi: 10.1159/000358824 PMID: 24992985
  80. Felmingham, K.L.; Zuj, D.V.; Hsu, K.C.M.; Nicholson, E.; Palmer, M.A.; Stuart, K.; Vickers, J.C.; Malhi, G.S.; Bryant, R.A. The BDNF Val66Met polymorphism moderates the relationship between Posttraumatic Stress Disorder and fear extinction learning. Psychoneuroendocrinology, 2018, 91, 142-148. doi: 10.1016/j.psyneuen.2018.03.002 PMID: 29550677
  81. Giza, J.I.; Kim, J.; Meyer, H.C.; Anastasia, A.; Dincheva, I.; Zheng, C.I.; Lopez, K.; Bains, H.; Yang, J.; Bracken, C.; Liston, C.; Jing, D.; Hempstead, B.L.; Lee, F.S. The BDNF val66met prodomain disassembles dendritic spines altering fear extinction circuitry and behavior. Neuron, 2018, 99(1), 163-178.e6. doi: 10.1016/j.neuron.2018.05.024 PMID: 29909994
  82. Mühlberger, A.; Andreatta, M.; Ewald, H.; Glotzbach-Schoon, E.; Tröger, C.; Baumann, C.; Reif, A.; Deckert, J.; Pauli, P. The BDNF Val66Met polymorphism modulates the generalization of cued fear responses to a novel context. Neuropsychopharmacology, 2014, 39(5), 1187-1195. doi: 10.1038/npp.2013.320 PMID: 24247044
  83. Soliman, F.; Glatt, C.E.; Bath, K.G.; Levita, L.; Jones, R.M.; Pattwell, S.S.; Jing, D.; Tottenham, N.; Amso, D.; Somerville, L.H.; Voss, H.U.; Glover, G.; Ballon, D.J.; Liston, C.; Teslovich, T.; Van Kempen, T.; Lee, F.S.; Casey, B.J. A genetic variant BDNF polymorphism alters extinction learning in both mouse and human. Science, 2010, 327(5967), 863-866. doi: 10.1126/science.1181886 PMID: 20075215
  84. Lonsdorf, T.B.; Golkar, A.; Lindström, K.M.; Haaker, J.; Öhman, A.; Schalling, M.; Ingvar, M. BDNF val66met affects neural activation pattern during fear conditioning and 24 h delayed fear recall. Soc. Cogn. Affect. Neurosci., 2015, 10(5), 664-671. doi: 10.1093/scan/nsu102 PMID: 25103087
  85. Lonsdorf, T.B.; Weike, A.I.; Golkar, A.; Schalling, M.; Hamm, A.O.; Öhman, A. Amygdala-dependent fear conditioning in humans is modulated by the BDNFval66met polymorphism. Behav. Neurosci., 2010, 124(1), 9-15. doi: 10.1037/a0018261 PMID: 20141276
  86. Asthana, M.K.; Brunhuber, B.; Mühlberger, A.; Reif, A.; Schneider, S.; Herrmann, M.J. Preventing the return of fear using reconsolidation update mechanisms depends on the met-allele of the brain derived neurotrophic factor val66met polymorphism. Int. J. Neuropsychopharmacol., 2015, 19(6), pyv137. doi: 10.1093/ijnp/pyv137 PMID: 26721948
  87. Jaehne, E.J.; Kent, J.N.; Antolasic, E.J.; Wright, B.J.; Spiers, J.G.; Creutzberg, K.C.; De Rosa, F.; Riva, M.A.; Sortwell, C.E.; Collier, T.J.; van den Buuse, M. Behavioral phenotyping of a rat model of the BDNF Val66Met polymorphism reveals selective impairment of fear memory. Transl. Psychiatry, 2022, 12(1), 93. doi: 10.1038/s41398-022-01858-5 PMID: 35256586
  88. Long, V.A.; Fanselow, M.S. Stress-enhanced fear learning in rats is resistant to the effects of immediate massed extinction. Stress, 2012, 15(6), 627-636. doi: 10.3109/10253890.2011.650251 PMID: 22176467
  89. Raju, S.; Notaras, M.; Grech, A.M.; Schroeder, A.; van den Buuse, M.; Hill, R.A. BDNF Val66Met genotype and adolescent glucocorticoid treatment induce sex-specific disruptions to fear extinction and amygdala GABAergic interneuron expression in mice. Horm. Behav., 2022, 144, 105231. doi: 10.1016/j.yhbeh.2022.105231 PMID: 35779519
  90. Notaras, M.; Hill, R.; Gogos, J.A.; van den Buuse, M. BDNF Val66Met genotype determines hippocampus-dependent behavior via sensitivity to glucocorticoid signaling. Mol. Psychiatry, 2016, 21(6), 730-732. doi: 10.1038/mp.2015.152 PMID: 26821977
  91. Corrone, M.; Ratnayake, R.; De Oliveira, N.; Jaehne, E.J.; van den Buuse, M. Methamphetamine-induced locomotor sensitization in mice is not associated with deficits in a range of cognitive, affective and social behaviours: Interaction with brain-derived neurotrophic factor (BDNF) Val66Met. Behav. Pharmacol., 2022, 34(1), 20-36.
  92. Richter-Levin, G.; Stork, O.; Schmidt, M.V. Animal models of PTSD: A challenge to be met. Mol. Psychiatry, 2019, 24(8), 1135-1156. doi: 10.1038/s41380-018-0272-5 PMID: 30816289
  93. Osterburg, A.R.; Hexley, P.; Supp, D.M.; Robinson, C.T.; Noel, G.; Ogle, C.; Boyce, S.T.; Aronow, B.J.; Babcock, G.F. Concerns over interspecies transcriptional comparisons in mice and humans after trauma. Proc. Natl. Acad. Sci. USA, 2013, 110(36), E3370. doi: 10.1073/pnas.1306033110 PMID: 23847210
  94. Cohen, H.; Geva, A.B.; Matar, M.A.; Zohar, J.; Kaplan, Z. Post-traumatic stress behavioural responses in inbred mouse strains: can genetic predisposition explain phenotypic vulnerability? Int. J. Neuropsychopharmacol., 2008, 11(3), 331-349. doi: 10.1017/S1461145707007912 PMID: 17655807
  95. Shansky, R.M. Sex differences in PTSD resilience and susceptibility: Challenges for animal models of fear learning. Neurobiol. Stress, 2015, 1, 60-65.
  96. Dai, W.; Kaminga, A.C.; Wu, X.; Wen, S.W.; Tan, H.; Yan, J.; Deng, J.; Lai, Z.; Liu, A. Brain-derived neurotropic factor val66met polymorphism and posttraumatic stress disorder among survivors of the 1998 Dongting lake flood in China. BioMed Res. Int., 2017, 2017, 1-9. doi: 10.1155/2017/4569698 PMID: 28589140
  97. Guo, J.C.; Yang, Y.J.; Zheng, J.F.; Guo, M.; Wang, X.D.; Gao, Y.S.; Fu, L.Q.; Jiang, X.L.; Fu, L.M.; Huang, T. Functional rs6265 polymorphism in the brain‐derived neurotrophic factor gene confers protection against neurocognitive dysfunction in posttraumatic stress disorder among Chinese patients with hepatocellular carcinoma. J. Cell. Biochem., 2019, 120(6), 10434-10443. doi: 10.1002/jcb.28328 PMID: 30659644
  98. Young, D.A.; Neylan, T.C.; O’Donovan, A.; Metzler, T.; Richards, A.; Ross, J.A.; Inslicht, S.S. The interaction of BDNF Val66Met, PTSD, and child abuse on psychophysiological reactivity and HPA axis function in a sample of Gulf War Veterans. J. Affect. Disord., 2018, 235, 52-60. doi: 10.1016/j.jad.2018.04.004 PMID: 29649711
  99. Li, R.H.; Fan, M.; Hu, M.S.; Ran, M.S.; Fang, D.Z. Reduced severity of posttraumatic stress disorder associated with Val allele of Val66Met polymorphism at brain-derived neurotrophic factor gene among Chinese adolescents after Wenchuan earthquake. Psychophysiology, 2016, 53(5), 705-711. doi: 10.1111/psyp.12603 PMID: 26751724
  100. Zhang, L.; Benedek, D.M.; Fullerton, C.S.; Forsten, R.D.; Naifeh, J.A.; Li, X.X.; Hu, X.Z.; Li, H.; Jia, M.; Xing, G.Q.; Benevides, K.N.; Ursano, R.J. PTSD risk is associated with BDNF Val66Met and BDNF overexpression. Mol. Psychiatry, 2014, 19(1), 8-10. doi: 10.1038/mp.2012.180 PMID: 23319005
  101. Nedic Erjavec, G.; Nikolac Perkovic, M.; Tudor, L.; Uzun, S.; Kovacic Petrovic, Z.; Konjevod, M.; Sagud, M.; Kozumplik, O.; Svob Strac, D.; Peraica, T.; Mimica, N.; Havelka, M.A.; Zilic, D.; Pivac, N. Moderating effects of BDNF genetic variants and smoking on cognition in PTSD veterans. Biomolecules, 2021, 11(5), 641. doi: 10.3390/biom11050641 PMID: 33926045
  102. Dretsch, M.N.; Williams, K.; Emmerich, T.; Crynen, G.; Ait-Ghezala, G.; Chaytow, H.; Mathura, V.; Crawford, F.C.; Iverson, G.L. Brain‐derived neurotropic factor polymorphisms, traumatic stress, mild traumatic brain injury, and combat exposure contribute to postdeployment traumatic stress. Brain Behav., 2016, 6(1), e00392. doi: 10.1002/brb3.392 PMID: 27110438
  103. Pivac, N.; Kozaric-Kovacic, D.; Grubisic-Ilic, M.; Nedic, G.; Rakos, I.; Nikolac, M.; Blazev, M.; Muck-Seler, D. The association between brain-derived neurotrophic factor Val66Met variants and psychotic symptoms in posttraumatic stress disorder. World J. Biol. Psychiatry, 2012, 13(4), 306-311. doi: 10.3109/15622975.2011.582883 PMID: 21728904
  104. Felmingham, K.L.; Dobson-Stone, C.; Schofield, P.R.; Quirk, G.J.; Bryant, R.A. The brain-derived neurotrophic factor val66met polymorphism predicts response to exposure therapy in posttraumatic stress disorder. Biol. Psychiatry, 2013, 73(11), 1059-1063. doi: 10.1016/j.biopsych.2012.10.033
  105. Lyoo, I.K.; Kim, J.E.; Yoon, S.J.; Hwang, J.; Bae, S.; Kim, D.J. The neurobiological role of the dorsolateral prefrontal cortex in recovery from trauma. Longitudinal brain imaging study among survivors of the South Korean subway disaster. Arch. Gen. Psychiatry, 2011, 68(7), 701-713. doi: 10.1001/archgenpsychiatry.2011.70 PMID: 21727254
  106. Jin, M.J.; Jeon, H.; Hyun, M.H.; Lee, S.H. Influence of childhood trauma and brain-derived neurotrophic factor Val66Met polymorphism on posttraumatic stress symptoms and cortical thickness. Sci. Rep., 2019, 9(1), 6028. doi: 10.1038/s41598-019-42563-6 PMID: 30988377
  107. van den Heuvel, L.; Suliman, S.; Malan-Müller, S.; Hemmings, S.; Seedat, S. Brain-derived neurotrophic factor Val66met polymorphism and plasma levels in road traffic accident survivors. Anxiety Stress Coping, 2016, 29(6), 616-629. doi: 10.1080/10615806.2016.1163545 PMID: 26999419
  108. Valente, N.L.M.; Vallada, H.; Cordeiro, Q.; Miguita, K.; Bressan, R.A.; Andreoli, S.B.; Mari, J.J.; Mello, M.F. Candidate-gene approach in posttraumatic stress disorder after urban violence: Association analysis of the genes encoding serotonin transporter, dopamine transporter, and BDNF. J. Mol. Neurosci., 2011, 44(1), 59-67. doi: 10.1007/s12031-011-9513-7 PMID: 21491204
  109. Bruenig, D.; Lurie, J.; Morris, C.P.; Harvey, W.; Lawford, B.; Young, R.M.; Voisey, J. A case-control study and meta-analysis reveal BDNF val66met is a possible risk factor for PTSD. Neural Plast., 2016, 2016, 1-10. doi: 10.1155/2016/6979435 PMID: 27413557
  110. Guo, J.C.; Yang, Y.J.; Guo, M.; Wang, X.D.; Juan, Y.; Gao, Y.S.; Fu, L.Q.; Jiang, X.L.; Fu, L.M.; Huang, T. Guo; Yang, Y.-J.; Guo, M.; Wang, X.-D.; Juan, Y.; Gao, Y.-S.; Fu, L.-Q.; Jiang, X.-L.; Fu, L.-M.; Huang, T., Correlations of four genetic single nucleotide polymorphisms in brain-derived neurotrophic factor with posttraumatic stress disorder. Psychiatry Investig., 2018, 15(4), 407-412. doi: 10.30773/pi.2017.06.17.1 PMID: 29551049
  111. Bountress, K.E.; Bacanu, S.A.; Tomko, R.L.; Korte, K.J.; Hicks, T.; Sheerin, C.; Lind, M.J.; Marraccini, M.; Nugent, N.; Amstadter, A.B. The effects of a BDNF val66met polymorphism on posttraumatic stress disorder: A meta-analysis. Neuropsychobiology, 2017, 76(3), 136-142. doi: 10.1159/000489407 PMID: 29874672
  112. Tudor, L.; Konjevod, M.; Nikolac Perkovic, M.; Svob Strac, D.; Nedic Erjavec, G.; Uzun, S.; Kozumplik, O.; Sagud, M.; Kovacic Petrovic, Z.; Pivac, N. Genetic variants of the brain-derived neurotrophic factor and metabolic indices in veterans with posttraumatic stress disorder. Front. Psychiatry, 2018, 9, 637. doi: 10.3389/fpsyt.2018.00637 PMID: 30542302
  113. Dinoff, A.; Herrmann, N.; Swardfager, W.; Lanctôt, K.L. The effect of acute exercise on blood concentrations of brain-derived neurotrophic factor in healthy adults: A meta-analysis. Eur. J. Neurosci., 2017, 46(1), 1635-1646. doi: 10.1111/ejn.13603 PMID: 28493624
  114. Patki, G.; Li, L.; Allam, F.; Solanki, N.; Dao, A.T.; Alkadhi, K.; Salim, S. Moderate treadmill exercise rescues anxiety and depression-like behavior as well as memory impairment in a rat model of posttraumatic stress disorder. Physiol. Behav., 2014, 130, 47-53. doi: 10.1016/j.physbeh.2014.03.016
  115. Vaynman, S.; Ying, Z.; Gomez-Pinilla, F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur. J. Neurosci., 2004, 20(10), 2580-2590. doi: 10.1111/j.1460-9568.2004.03720.x PMID: 15548201
  116. Fang, Z.H.; Lee, C.H.; Seo, M.K.; Cho, H.; Lee, J.G.; Lee, B.J.; Park, S.W.; Kim, Y.H. Effect of treadmill exercise on the BDNF-mediated pathway in the hippocampus of stressed rats. Neurosci. Res., 2013, 76(4), 187-194. doi: 10.1016/j.neures.2013.04.005 PMID: 23665137
  117. Lu, J.; Xu, Y.; Hu, W.; Gao, Y.; Ni, X.; Sheng, H.; Liu, Y. Exercise ameliorates depression-like behavior and increases hippocampal BDNF level in ovariectomized rats. Neurosci. Lett., 2014, 573, 13-18. doi: 10.1016/j.neulet.2014.04.053
  118. Marais, L.; Stein, D.J.; Daniels, W.M.U. Exercise increases BDNF levels in the striatum and decreases depressive-like behavior in chronically stressed rats. Metab. Brain Dis., 2009, 24(4), 587-597. doi: 10.1007/s11011-009-9157-2 PMID: 19844781
  119. Marlatt, M.W.; Potter, M.C.; Lucassen, P.J.; van Praag, H. Running throughout middle-age improves memory function, hippocampal neurogenesis, and BDNF levels in female C57BL/6J mice. Dev. Neurobiol., 2012, 72(6), 943-952. doi: 10.1002/dneu.22009 PMID: 22252978
  120. Shafia, S.; Vafaei, A.A.; Samaei, S.A.; Bandegi, A.R.; Rafiei, A.; Valadan, R.; Hosseini-Khah, Z.; Mohammadkhani, R.; Rashidy-Pour, A. Effects of moderate treadmill exercise and fluoxetine on behavioural and cognitive deficits, hypothalamic-pituitary-adrenal axis dysfunction and alternations in hippocampal BDNF and mRNA expression of apoptosis – related proteins in a rat model of post-traumatic stress disorder. Neurobiol. Learn. Mem., 2017, 139, 165-178. doi: 10.1016/j.nlm.2017.01.009 PMID: 28137660
  121. Neeper, S.A.; Gómez-Pinilla, F.; Choi, J.; Cotman, C.W. Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res., 1996, 726(1-2), 49-56. doi: 10.1016/0006-8993(96)00273-9 PMID: 8836544
  122. Sun, L.; Cui, K.; Xing, F.; Liu, X. Akt dependent adult hippocampal neurogenesis regulates the behavioral improvement of treadmill running to mice model of post-traumatic stress disorder. Behav. Brain Res., 2020, 379, 112375. doi: 10.1016/j.bbr.2019.112375 PMID: 31759046
  123. van Praag, H. Neurogenesis and exercise: past and future directions. Neuromol. Med., 2008, 10(2), 128-140. doi: 10.1007/s12017-008-8028-z PMID: 18286389
  124. Nowacka-Chmielewska, M.; Grabowska, K.; Grabowski, M.; Meybohm, P.; Burek, M.; Małecki, A. Running from stress: Neurobiological mechanisms of exercise-induced stress resilience. Int. J. Mol. Sci., 2022, 23(21), 13348. doi: 10.3390/ijms232113348 PMID: 36362131
  125. Ishikawa, R.; Uchida, C.; Kitaoka, S.; Furuyashiki, T.; Kida, S. Improvement of PTSD-like behavior by the forgetting effect of hippocampal neurogenesis enhancer memantine in a social defeat stress paradigm. Mol. Brain, 2019, 12(1), 68. doi: 10.1186/s13041-019-0488-6 PMID: 31370877
  126. Schoenfeld, T.J.; Rhee, D.; Martin, L.; Smith, J.A.; Sonti, A.N.; Padmanaban, V.; Cameron, H.A. New neurons restore structural and behavioral abnormalities in a rat model of PTSD. Hippocampus, 2019, 29(9), 848-861. doi: 10.1002/hipo.23087 PMID: 30865372
  127. Powers, M.B.; Medina, J.L.; Burns, S.; Kauffman, B.Y.; Monfils, M.; Asmundson, G.J.; Diamond, A.; McIntyre, C.; Smits, J.A. Exercise augmentation of exposure therapy for PTSD: Rationale and pilot efficacy data. Cogn. Behav. Ther., 2015, 44(4), 314-327.
  128. Crombie, K.M.; Sartin-Tarm, A.; Sellnow, K.; Ahrenholtz, R.; Lee, S.; Matalamaki, M.; Almassi, N.E.; Hillard, C.J.; Koltyn, K.F.; Adams, T.G.; Cisler, J.M. Exercise-induced increases in Anandamide and BDNF during extinction consolidation contribute to reduced threat following reinstatement: Preliminary evidence from a randomized controlled trial. Psychoneuroendocrinology, 2021, 132, 105355. doi: 10.1016/j.psyneuen.2021.105355 PMID: 34280820
  129. Szuhany, K.L.; Bugatti, M.; Otto, M.W. A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J. Psychiatr. Res., 2015, 60, 56-64. doi: 10.1016/j.jpsychires.2014.10.003 PMID: 25455510
  130. Hu, S.; Tucker, L.; Wu, C.; Yang, L. Beneficial effects of exercise on depression and anxiety during the COVID-19 pandemic: A narrative review. Front. Psychiatry, 2020, 11, 587557. doi: 10.3389/fpsyt.2020.587557 PMID: 33329133
  131. Ruiz-González, D.; Hernández-Martínez, A.; Valenzuela, P.L.; Morales, J.S.; Soriano-Maldonado, A. Effects of physical exercise on plasma brain-derived neurotrophic factor in neurodegenerative disorders: A systematic review and meta-analysis of randomized controlled trials. Neurosci. Biobehav. Rev., 2021, 128, 394-405. doi: 10.1016/j.neubiorev.2021.05.025 PMID: 34087277
  132. Cavalcante, B.R.R.; Improta-Caria, A.C.; Melo, V.H.; De Sousa, R.A.L. Exercise-linked consequences on epilepsy. Epilepsy Behav., 2021, 121(Pt A), 108079. doi: 10.1016/j.yebeh.2021.108079 PMID: 34058490
  133. Murawska-Ciałowicz, E.; Wiatr, M.; Ciałowicz, M.; Gomes de Assis, G.; Borowicz, W.; Rocha-Rodrigues, S.; Paprocka-Borowicz, M.; Marques, A. BDNF impact on biological markers of depression - Role of physical exercise and training. Int. J. Environ. Res. Public Health, 2021, 18(14), 7553. doi: 10.3390/ijerph18147553 PMID: 34300001
  134. Jaehne, E.J.; Kent, J.N.; Lam, N.; Schonfeld, L.; Spiers, J.G.; Begni, V.; De Rosa, F.; Riva, M.A.; van den Buuse, M. Chronic running‐wheel exercise from adolescence leads to increased anxiety and depression‐like phenotypes in adulthood in rats: Effects on stress markers and interaction with BDNF Val66Met genotype. Dev. Psychobiol., 2023, 65(1), e22347. doi: 10.1002/dev.22347 PMID: 36567651
  135. Nascimento, C.M.C.; Pereira, J.R.; Pires de Andrade, L.; Garuffi, M.; Ayan, C.; Kerr, D.S.; Talib, L.L.; Cominetti, M.R.; Stella, F. Physical exercise improves peripheral BDNF levels and cognitive functions in mild cognitive impairment elderly with different bdnf Val66Met genotypes. J. Alzheimers Dis., 2014, 43(1), 81-91. doi: 10.3233/JAD-140576 PMID: 25062900
  136. Rahman, M.S.; Millischer, V.; Zeebari, Z.; Forsell, Y.; Lavebratt, C. BDNF Val66Met and childhood adversity on response to physical exercise and internet-based cognitive behavioural therapy in depressed Swedish adults. J. Psychiatr. Res., 2017, 93, 50-58.
  137. Kim, J.M.; Stewart, R.; Bae, K.Y.; Kim, S.W.; Yang, S.J.; Park, K.H.; Shin, I.S.; Yoon, J.S. Role of BDNF val66met polymorphism on the association between physical activity and incident dementia. Neurobiol. Aging, 2011, 32(3), 551.e5-12. doi: 10.1016/j.neurobiolaging.2010.01.018
  138. Liu, T.; Canon, M.D.; Shen, L.; Marples, B.A.; Colton, J.P.; Lo, W.J.; Gray, M.; Li, C. The influence of the BDNF Val66Met polymorphism on the association of regular physical activity with cognition among individuals with diabetes. Biol. Res. Nurs., 2021, 23(3), 318-330. doi: 10.1177/1099800420966648 PMID: 33063528
  139. Zarza-Rebollo, J.A.; Molina, E.; López-Isac, E.; Pérez-Gutiérrez, A.M.; Gutiérrez, B.; Cervilla, J.A.; Rivera, M. Interaction effect between physical activity and the BDNF Val66Met polymorphism on depression in women from the PISMA-ep study. Int. J. Environ. Res. Public Health, 2022, 19(4), 2068. doi: 10.3390/ijerph19042068 PMID: 35206257
  140. Mata, J.; Thompson, R.J.; Gotlib, I.H. BDNF genotype moderates the relation between physical activity and depressive symptoms. Health Psychol., 2010, 29(2), 130-133. doi: 10.1037/a0017261 PMID: 20230085
  141. Takeuchi, H.; Tomita, H.; Taki, Y.; Kikuchi, Y.; Ono, C.; Yu, Z.; Sekiguchi, A.; Nouchi, R.; Kotozaki, Y.; Nakagawa, S.; Miyauchi, C.M.; Iizuka, K.; Yokoyama, R.; Shinada, T.; Yamamoto, Y.; Hanawa, S.; Araki, T.; Kunitoki, K.; Sassa, Y.; Kawashima, R. Effect of the interaction between BDNF Val66Met polymorphism and daily physical activity on mean diffusivity. Brain Imaging Behav., 2020, 14(3), 806-820. doi: 10.1007/s11682-018-0025-8 PMID: 30617785
  142. Caldwell, H.A.E.; Bryan, A.D.; Hagger, M.S. What keeps a body moving? The brain-derived neurotrophic factor val66met polymorphism and intrinsic motivation to exercise in humans. J. Behav. Med., 2014, 37(6), 1180-1192. doi: 10.1007/s10865-014-9567-4 PMID: 24805993
  143. Ieraci, A.; Madaio, A.I.; Mallei, A.; Lee, F.S.; Popoli, M. Brain-derived neurotrophic factor val66met human polymorphism impairs the beneficial exercise-induced neurobiological changes in mice. Neuropsychopharmacology, 2016, 41(13), 3070-3079. doi: 10.1038/npp.2016.120 PMID: 27388329
  144. Lemos, J.R., Jr; Alves, C.R.; de Souza, S.B.C.; Marsiglia, J.D.C.; Silva, M.S.M.; Pereira, A.C.; Teixeira, A.L.; Vieira, E.L.M.; Krieger, J.E.; Negrão, C.E.; Alves, G.B.; de Oliveira, E.M.; Bolani, W.; Dias, R.G.; Trombetta, I.C. Peripheral vascular reactivity and serum BDNF responses to aerobic training are impaired by the BDNF Val66Met polymorphism. Physiol. Genomics, 2016, 48(2), 116-123. doi: 10.1152/physiolgenomics.00086.2015 PMID: 26603150
  145. Watts, A.; Andrews, S.J.; Anstey, K.J. Sex differences in the impact of BDNF genotype on the longitudinal relationship between physical activity and cognitive performance. Gerontology, 2018, 64(4), 361-372. doi: 10.1159/000486369 PMID: 29402782
  146. Helm, E.E.; Matt, K.S.; Kirschner, K.F.; Pohlig, R.T.; Kohl, D.; Reisman, D.S. The influence of high intensity exercise and the Val66Met polymorphism on circulating BDNF and locomotor learning. Neurobiol. Learn. Mem., 2017, 144, 77-85. doi: 10.1016/j.nlm.2017.06.003 PMID: 28668279
  147. Keyan, D.; Bryant, R.A. Acute exercise-induced enhancement of fear inhibition is moderated by BDNF Val66Met polymorphism. Transl. Psychiatry, 2019, 9(1), 131. doi: 10.1038/s41398-019-0464-z PMID: 30967530
  148. Pitts, B.L.; Whealin, J.M.; Harpaz-Rotem, I.; Duman, R.S.; Krystal, J.H.; Southwick, S.M.; Pietrzak, R.H. BDNF Val66Met polymorphism and posttraumatic stress symptoms in U.S. military veterans: Protective effect of physical exercise. Psychoneuroendocrinology, 2019, 100, 198-202. doi: 10.1016/j.psyneuen.2018.10.011 PMID: 30388593
  149. Keyan, D.; Bryant, R.A. Role of BDNF val66met polymorphism in modulating exercised-induced emotional memories. Psychoneuroendocrinology, 2017, 77, 150-157. doi: 10.1016/j.psyneuen.2016.12.013 PMID: 28056410

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