Brain-Derived Neurotrophic Factor Delivered Intranasally Relieves Post-Traumatic Stress Disorder Symptoms Caused by a Single Prolonged Stress in Rats

Zhang L.a,b· Deng L.a,c· Ma C.b· Zhang H.d· Dang Y.a,e

Author affiliations

aCollege of Medicine and Forensics, Xi’an Jiaotong University Health Science Center, Xi’an, China
bXi’an Center for Disease Control and Prevention, Xi’an, China
cDepartment of Psychiatry, First Affiliated Hospital of Xi’an Jiaotong University Health Science Center, Xi’an, China
dXi’an Mental Health Center, Xi’an, China
eKey Laboratory of the Health Ministry for Forensic Medicine, Xi’an Jiaotong University Health Science Center, Xi’an, China

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Article / Publication Details

First-Page Preview

Abstract of Research Article

Received: March 02, 2022
Accepted: December 12, 2022
Published online: January 11, 2023

Number of Print Pages: 11
Number of Figures: 8
Number of Tables: 0

ISSN: 0302-282X (Print)
eISSN: 1423-0224 (Online)

For additional information: https://www.karger.com/NPS

Abstract

Introduction: In our previous study, we successfully constructed the recombinant brain-derived neurotrophic factor (BDNF)-adeno-associated virus (AAV) modified by the influenza virus hemagglutinin-2 (HA2) and trans-transcriptional activator (TAT). BDNF-HA2TAT/AAV has been confirmed to have antidepression effects. BDNF-HA2TAT/AAV seems a promising therapy for post-traumatic stress disorder (PTSD) as the BDNF plays an important role in the function of the nervous system. However, the effects of BDNF-HA2TAT/AAV on PTSD caused by the single prolonged stress (SPS) model are unknown. Methods: After the SPS model was established, BDNF-HA2TAT/AAV was administered (1 × 1011 vg per rat) through inhalation in the SPS + BDNF group for 2 weeks. Next, the rats underwent behavioral tests including an open-field test (OFT), elevated plus maze (EPM), and a forced swimming test (FST). Sera and hippocampi were obtained from the rats, and an enzyme-linked immune sorbent assay was performed to determine corticosterone concentration. Western blotting was conducted to determine BDNF, tyrosine kinase receptor B (TrkB), cAMP-response element-binding protein, and protein kinase B levels. Results: BDNF-HA2TAT/AAV released anxiety-like and depression-like behaviors in OFT, EPM, and FST. BDNF-HA2TAT/AAV also results in high plasma concentrations of corticosterone, BDNF, and TrkB in the hippocampus. Conclusions: SPS is an excellent animal model to assess PTSD. BDNF-HA2TAT/AAV therapeutically effects PTSD caused by SPS, with changes seen in plasma corticosterone and BDNF-TrkB pathways within the hippocampus; therefore, BDNF-HA2TAT/AAV may be a promising treatment for patients with PTSD.

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References Thakur GS, Daigle BJ Jr., Dean KR, Zhang Y, Rodriguez-Fernandez M, Hammamieh R, et al. Systems biology approach to understanding post-traumatic stress disorder. Mol Biosyst. 2015;11(4):980–93. Langford DJ, Theodore BR, Balsiger D, Tran C, Doorenbos AZ, Tauben DJ, et al. Number and type of post-traumatic stress disorder symptom domains are associated with patient-reported outcomes in patients with chronic pain. J Pain. 2018;19(5):506–14. Righy C, Rosa RG, da Silva RTA, Kochhann R, Migliavaca CB, Robinson CC, et al. Prevalence of post-traumatic stress disorder symptoms in adult critical care survivors: a systematic review and meta-analysis. Crit Care. 2019;23(1):213. Koenen KC, Ratanatharathorn A, Ng L, McLaughlin KA, Bromet EJ, Stein DJ, et al. Posttraumatic stress disorder in the world mental health surveys. Psychol Med. 2017;47(13):2260–74. Knox D, George SA, Fitzpatrick CJ, Rabinak CA, Maren S, Liberzon I. Single prolonged stress disrupts retention of extinguished fear in rats. Learn Mem. 2012;19(2):43–9. Keller SM, Schreiber WB, Stanfield BR, Knox D. Inhibiting corticosterone synthesis during fear memory formation exacerbates cued fear extinction memory deficits within the single prolonged stress model. Behav Brain Res. 2015;287:182–6. Flandreau EI, Toth M. Animal models of PTSD: a critical review. Curr Top Behav Neurosci. 2018;38:47–68. Roberts NP, Roberts PA, Jones N, Bisson JI. Psychological interventions for post-traumatic stress disorder and comorbid substance use disorder: a systematic review and meta-analysis. Clin Psychol Rev. 2015;38:25–38. Kar N. Cognitive behavioral therapy for the treatment of post-traumatic stress disorder: a review. Neuropsychiatr Dis Treat. 2011;7:167–81. Lee DJ, Schnitzlein CW, Wolf JP, Vythilingam M, Rasmusson AM, Hoge CW. Psychotherapy versus pharmacotherapy for posttraumatic stress disorder: systemic review and meta-analyses to determine first-line treatments. Depress Anxiety. 2016;33(9):792–806. Forman-Hoffman V, Middleton JC, Feltner C, Gaynes BN, Weber RP, Bann C, et al. Psychological and pharmacological treatments for adults with posttraumatic stress disorder: a systematic review update. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018. Stein MBKNA, Kline NA, Matloff JL. Adjunctive olanzapine for SSRI-resistant combat-related PTSD: a double-blind, placebo-controlled study. Am J Psychiatry. 2002;159(10):1777–9. Di Lazzaro V, Profice P, Pilato F, Dileone M, Florio L, Tonali PA, et al. BDNF plasma levels in acute stroke. Neurosci Lett. 2007;422(2):128–30. Cesbron Y, Shaheen U, Free P, Levy R. TAT and HA2 facilitate cellular uptake of gold nanoparticles but do not lead to cytosolic localisation. PLoS One. 2015;10(4):e0121683. Xu R, Dong Y, Wang L, Tao X, Sun A, Wei D, et al. TAT-RhoGDI2, a novel tumor metastasis suppressor fusion protein: expression, purification and functional evaluation. Appl Microbiol Biotechnol. 2014;98(23):9633–41. Wang Y, Fu L, Liu B, Wang X, Wang K, Ye M. Construction of human LRIG1-TAT fusions and TAT-mediated LRIG1 protein delivery. Biomed Pharmacother. 2015;69:396–401. Ma XC, Liu P, Zhang XL, Jiang WH, Jia M, Wang CX, et al. Intranasal delivery of recombinant AAV containing BDNF fused with HA2TAT: a potential promising therapy strategy for major depressive disorder. Sci Rep. 2016;6:22404. Chen C, Dong Y, Liu F, Gao C, Ji C, Dang Y, et al. A study of antidepressant effect and mechanism on intranasal delivery of BDNF-ha2tat/AAV to rats with post-stroke depression. Neuropsychiatr Dis Treat. 2020;16:637–49. Esvald EE, Tuvikene J, Sirp A, Patil S, Bramham CR, Timmusk T. CREB family transcription factors are major mediators of BDNF transcriptional autoregulation in cortical neurons. J Neurosci. 2020;40(7):1405–26. Duan B, Liu DS, Huang Y, Zeng WZ, Wang X, Yu H, et al. PI3-kinase/Akt pathway-regulated membrane insertion of acid-sensing ion channel 1a underlies BDNF-induced pain hypersensitivity. J Neurosci. 2012;32(18):6351–63. Andero R, Daviu N, Escorihuela RM, Nadal R, Armario A. 7, 8-dihydroxyflavone, a TrkB receptor agonist, blocks long-term spatial memory impairment caused by immobilization stress in rats. Hippocampus. 2012;22(3):399–408. Homiack D, O’Cinneide E, Hajmurad S, Barrileaux B, Stanley M, Kreutz MR, et al. Predator odor evokes sex-independent stress responses in male and female Wistar rats and reduces phosphorylation of cyclic-adenosine monophosphate response element binding protein in the male, but not the female hippocampus. Hippocampus. 2017;27(9):1016–29. Wang J, Gao F, Cui S, Yang S, Gao F, Wang X, et al. Utility of 7, 8-dihydroxyflavone in preventing astrocytic and synaptic deficits in the hippocampus elicited by PTSD. Pharmacol Res. 2022;176:106079. Kinlein SA, Phillips DJ, Keller CR, Karatsoreos IN. Role of corticosterone in altered neurobehavioral responses to acute stress in a model of compromised hypothalamic-pituitary-adrenal axis function. Psychoneuroendocrinology. 2019;102:248–55. Spencer RL, Deak T. A users guide to HPA axis research. Physiol Behav. 2017;178:43–65. Harnett NG, Goodman AM, Knight DC. PTSD-related neuroimaging abnormalities in brain function, structure, and biochemistry. Exp Neurol. 2020;330:113331. Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM, et al. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry. 1995;152(7):973–81. Milad MR, Pitman RK, Ellis CB, Gold AL, Shin LM, Lasko NB, et al. Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry. 2009;66(12):1075–82. Shin LM, Whalen PJ, Pitman RK, Bush G, Macklin ML, Lasko NB, et al. An fMRI study of anterior cingulate function in posttraumatic stress disorder. Biol Psychiatry. 2001;50(12):932–42. Shin LM, Rauch SL, Pitman RK. Amygdala, medial prefrontal cortex, and hippocampal function in PTSD. Ann N Y Acad Sci. 2006;1071:67–79. Willner P. The validity of animal models of depression. Psychopharmacology. 1984;83:1–16. Yehuda RAS, Antelman SM. Criteria for rationally evaluating animal models of posttraumatic stress disorder. Biol Psychiatry. 1993;33(7):479–86. Wakizono T, Sawamura T, Shimizu K, Nibuya M, Suzuki G, Toda H, et al. Stress vulnerabilities in an animal model of post-traumatic stress disorder. Physiol Behav. 2007;90(4):687–95. Cohen H, Zohar J, Matar MA, Zeev K, Loewenthal U, Richter-Levin G. Setting apart the affected: the use of behavioral criteria in animal models of post traumatic stress disorder. Neuropsychopharmacology. 2004;29(11):1962–70. Adamec R, Muir C, Grimes M, Pearcey K. Involvement of noradrenergic and corticoid receptors in the consolidation of the lasting anxiogenic effects of predator stress. Behav Brain Res. 2007;179(2):192–207. Yamamoto S, Morinobu S, Takei S, Fuchikami M, Matsuki A, Yamawaki S, et al. Single prolonged stress: toward an animal model of posttraumatic stress disorder. Depress Anxiety. 2009;26(12):1110–7. Daskalakis NP, Yehuda R, Diamond DM. Animal models in translational studies of PTSD. Psychoneuroendocrinology. 2013;38(9):1895–911. Berardi A, Trezza V, Campolongo C. Modeling specific phobias and posttraumatic stress disorder in rodents: the challenge to convey both cognitive and emotional features. Rev Neurosci. 2012;23(5–6):645–57. Deslauriers J, Toth M, Der-Avakian A, Risbrough VB. Current status of animal models of posttraumatic stress disorder: behavioral and biological phenotypes, and future challenges in improving translation. Biol Psychiatry. 2018;83(10):895–907. Knox D, Nault T, Henderson C, Liberzon I. Glucocorticoid receptors and extinction retention deficits in the single prolonged stress model. Neuroscience. 2012;223:163–73. Ardi Z, Albrecht A, Richter-Levin A, Saha R, Richter-Levin G. Behavioral profiling as a translational approach in an animal model of posttraumatic stress disorder. Neurobiol Dis. 2016;88:139–47. Vyas A, Mitra R, Shankaranarayana Rao BS, Chattarji S. Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J Neurosci. 2002;22(15):6810–8. Mitra R, Jadhav S, McEwen BS, Vyas A, Chattarji S. Stress duration modulates the spatiotemporal patterns of spine formation in the basolateral amygdala. Proc Natl Acad Sci U S A. 2005;102(26):9371–6. Wu Z, Tian Q, Li F, Gao J, Liu Y, Mao M, et al. Behavioral changes over time in post-traumatic stress disorder: insights from a rat model of single prolonged stress. Behav Processes. 2016;124:123–9. Imanaka A, Morinobu S, Toki S, Yamawaki S. Importance of early environment in the development of post-traumatic stress disorder-like behaviors. Behav Brain Res. 2006;173(1):129–37. Liberzon IKM, Krstov M, Young EA. Stress-restress: effects on ACTH and fast feedback. Psychoneuroendocrinology. 1997;22(6):443–53. Pitman RK, Rasmusson AM, Koenen KC, Shin LM, Orr SP, Gilbertson MW, et al. Biological studies of post-traumatic stress disorder. Nat Rev Neurosci. 2012;13(11):769–87. Yehuda R, Halligan SL, Bierer LM. Relationship of parental trauma exposure and PTSD to PTSD, depressive and anxiety disorders in offspring. J Psychiatr Res. 2001;35(5):261–70. Miao YL, Guo WZ, Shi WZ, Fang WW, Liu Y, Liu J, et al. Midazolam ameliorates the behavior deficits of a rat posttraumatic stress disorder model through dual 18 kDa translocator protein and central benzodiazepine receptor and neurosteroidogenesis. PLoS One. 2014;9(7):e101450. Hoskins M, Pearce J, Bethell A, Dankova L, Barbui C, Tol WA, et al. Pharmacotherapy for post-traumatic stress disorder: systematic review and meta-analysis. Br J Psychiatry. 2015;206(2):93–100. Martenyi F, Soldatenkova V. Fluoxetine in the acute treatment and relapse prevention of combat-related post-traumatic stress disorder: analysis of the veteran group of a placebo-controlled, randomized clinical trial. Eur Neuropsychopharmacol. 2006;16(5):340–9. Zohar JAD, Amital D, Miodownik C, Kotler M, Bleich A, Lane RM. Double-blind placebo-controlled pilot study of sertraline in military veterans with posttraumatic stress disorder. J Clin Psychopharmacol. 2002;22(2):190–5. Stein DJ, Ipser JC, Seedat S. Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2006;2006(1):CD002795. Huang ZD, Zhao YF, Li S, Gu HY, Lin LL, Yang ZY, et al. Comparative efficacy and acceptability of pharmaceutical management for adults with post-traumatic stress disorder: a systematic review and meta-analysis. Front Pharmacol. 2020;11:559. Szeszko PR, Lehrner A, Yehuda R. Glucocorticoids and hippocampal structure and function in PTSD. Harv Rev Psychiatry. 2018;26(3):142–57. Sapolsky RMKL, Krey LC, McEwen BS. The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev. 1986;7(3):284–301. Harvey BH, Brand L, Jeeva Z, Stein DJ. Cortical/hippocampal monoamines, HPA-axis changes and aversive behavior following stress and restress in an animal model of post-traumatic stress disorder. Physiol Behav. 2006;87(5):881–90. Yehuda R, Southwick SM, Nussbaum G, Wahby V, Giller EL Jr., Mason JW. Low urinary cortisol excretion in patients with posttraumatic stress disorder. J Nerv Ment Dis. 1990;178(6):366–9. Gurvits TV, Shenton ME, Hokama H, Ohta H, Lasko NB, Gilbertson MW, et al. Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder. Biol Psychiatry. 1996;40(11):1091–9. Stein MB, Koverola C, Hanna C, Torchia MG, McClarty B. Hippocampal volume in women victimized by childhood sexual abuse. Psychol Med. 1997;27(4):951–9. Kitayama N, Vaccarino V, Kutner M, Weiss P, Bremner JD. Magnetic resonance imaging (MRI) measurement of hippocampal volume in posttraumatic stress disorder: a meta-analysis. J Affect Disord. 2005;88(1):79–86. Bazak N, Kozlovsky N, Kaplan Z, Matar M, Golan H, Zohar J, et al. Pre-pubertal stress exposure affects adult behavioral response in association with changes in circulating corticosterone and brain-derived neurotrophic factor. Psychoneuroendocrinology. 2009;34(6):844–58. Hoffman JR, Ostfeld I, Stout JR, Harris RC, Kaplan Z, Cohen H. β-Alanine supplemented diets enhance behavioral resilience to stress exposure in an animal model of PTSD. Amino acids. 2015;47(6):1247–57. Kozlovsky N, Matar MA, Kaplan Z, Kotler M, Zohar J, Cohen H. Long-term down-regulation of BDNF mRNA in rat hippocampal CA1 subregion correlates with PTSD-like behavioural stress response. Int J Neuropsychopharmacol. 2007;10(6):741–58. Schaaf MJ, de Jong J, de Kloet ER, Vreugdenhil E. Downregulation of BDNF mRNA and protein in the rat hippocampus by corticosterone. Brain Res. 1998;813(1):112–20. Article / Publication Details

First-Page Preview

Abstract of Research Article

Received: March 02, 2022
Accepted: December 12, 2022
Published online: January 11, 2023

Number of Print Pages: 11
Number of Figures: 8
Number of Tables: 0

ISSN: 0302-282X (Print)
eISSN: 1423-0224 (Online)

For additional information: https://www.karger.com/NPS

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