Inhibiting Brd4 alleviated PTSD-like behaviors and fear memory through regulating immediate early genes expression and neuroinflammation in rats.
Animals
Anxiety
/ drug therapy
Azepines
/ pharmacology
Brain Chemistry
/ drug effects
Cues
Dendritic Spines
/ drug effects
Depression
/ drug therapy
Encephalitis
/ drug therapy
Fear
/ psychology
Gene Expression Regulation
/ drug effects
Genes, Immediate-Early
/ drug effects
Male
Memory
/ drug effects
Motor Activity
/ drug effects
Nuclear Proteins
/ antagonists & inhibitors
Rats
Rats, Wistar
Stress Disorders, Post-Traumatic
/ drug therapy
Transcription Factors
/ antagonists & inhibitors
Triazoles
/ pharmacology
Brd4
immediate early gene
inescapable foot shock
microglia
post-traumatic stress disorder
pro-inflammatory cytokines
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
11
05
2021
received:
30
01
2021
accepted:
18
05
2021
pubmed:
30
5
2021
medline:
12
11
2021
entrez:
29
5
2021
Statut:
ppublish
Résumé
Post-traumatic stress disorder (PTSD) is characterized by depression/anxiety and memory failure, primarily fear memory. According to the reports, neuroinflammation and synaptic plasticity can play a role in the neurophysiological mechanisms underlying PTSD. Bromodomain-containing protein 4 (Brd4) intriguingly affects regulating of inflammatory responses and learning and memory. This study aimed to explore the effect of inhibiting Brd4 on depression/anxiety-like behaviors, spatial and fear memory, and underlying mechanisms in a model of PTSD. Inescapable foot shocks (IFS) with a sound reminder in 6 days were used to induce PTSD-like behaviors which were tested using contextual and cue fear tests, sucrose preference test, open-field test, elevated plus maze test, and Y-maze test. Meanwhile, the Brd4 inhibitor JQ1 was used as an intervention. The results found that IFS induced PTSD-like behaviors and indicated obvious Brd4 expression in microglia of the prefrontal cortex (PFC), hippocampus, and amygdala, pro-inflammatory cytokines over-expression, microglial activation, and nuclear factor-kappa B over-expression in PFC and hippocampus but not in amygdala. Meanwhile, the alterations of immediate early genes (IEGs) were found in PFC, hippocampus, and amygdala. Besides, dendritic spine density was reduced in PFC and hippocampus but was elevated in amygdala of rats with IFS. In addition, treatment with JQ1 significantly reduced freezing time in the contextual and cue fear test, reversed the behavioral impairment, decreased the elevated neuroinflammation, and normalized the alteration in IEGs and dendritic spine densities. The results suggested that Brd4 was involved in IFS-induced PTSD-like behaviors through regulating neuroinflammation, dynamics of IEGs, and synaptic plasticity.
Substances chimiques
(+)-JQ1 compound
0
Azepines
0
Brd4 protein, rat
0
Nuclear Proteins
0
Transcription Factors
0
Triazoles
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
912-927Informations de copyright
© 2021 International Society for Neurochemistry.
Références
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders : DSM-IV-TR (American Psychiatric Association).
Bali, A., & Jaggi, A. S. (2015). Electric foot shock stress: A useful tool in neuropsychiatric studies. Reviews in the Neurosciences, 26, 655-677. https://doi.org/10.1515/revneuro-2015-0015
Barrett, E., Brothers, S., Wahlestedt, C., & Beurel, E. (2014). I-BET151 selectively regulates IL-6 production. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1842(9), 1549-1555. https://doi.org/10.1016/j.bbadis.2014.05.013
Benito, E., Ramachandran, B., Schroeder, H., Schmidt, G., Urbanke, H., Burkhardt, S., Capece, V., Dean, C., & Fischer, A. (2017). The BET/BRD inhibitor JQ1 improves brain plasticity in WT and APP mice. Translational Psychiatry, 7, e1239. https://doi.org/10.1038/tp.2017.202
Chau, L. S., Prakapenka, A., Fleming, S. A., Davis, A. S., & Galvez, R. (2013). Elevated Arc/Arg 3.1 protein expression in the basolateral amygdala following auditory trace-cued fear conditioning. Neurobiology of Learning and Memory, 106, 127-133. https://doi.org/10.1016/j.nlm.2013.07.010
Clarke, D. J., Chohan, T. W., Kassem, M. S., Smith, K. L., Chesworth, R., Karl, T., Kuligowski, M. P., Fok, S. Y., Bennett, M. R., & Arnold, J. C. (2019). Neuregulin 1 deficiency modulates adolescent stress-induced dendritic spine loss in a brain region-specific manner and increases complement 4 expression in the hippocampus. Schizophrenia Bulletin, 45, 339-349. https://doi.org/10.1093/schbul/sby029
Covington, H. E., Lobo, M. K., Maze, I., Vialou, V., Hyman, J. M., Zaman, S., LaPlant, Q., Mouzon, E., Ghose, S., Tamminga, C. A., Neve, R. L., Deisseroth, K., & Nestler, E. J. (2010). Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex. Journal of Neuroscience, 30, 16082-16090. https://doi.org/10.1523/JNEUROSCI.1731-10.2010
Dong, Y., Li, S., Lu, Y., Li, X., Liao, Y., Peng, Z., Li, Y., Hou, L., Yuan, Z., & Cheng, J. (2020). Stress-induced NLRP3 inflammasome activation negatively regulates fear memory in mice. Journal of Neuroinflammation, 17, 205. http://dx.doi.org/10.1186/s12974-020-01842-0
Duan, Q., Huang, F.-L., Li, S.-J., Chen, K.-Z., Gong, L., Qi, J., Yang, Z.-H., Yang, T., Li, F., & Li, C.-Q. (2020). BET proteins inhibitor JQ-1 impaired the extinction of remote auditory fear memory: An effect mediated by insulin like growth factor 2. Neuropharmacology, 177, 108255. https://doi.org/10.1016/j.neuropharm.2020.108255
Duclot, F., & Kabbaj, M. (2017). The role of early growth response 1 (EGR1) in brain plasticity and neuropsychiatric disorders. Frontiers in Behavioral Neuroscience, 11, 35. https://doi.org/10.3389/fnbeh.2017.00035
Enomoto, S., & Kato, T. A. (2021). Involvement of microglia in disturbed fear memory regulation: Possible microglial contribution to the pathophysiology of posttraumatic stress disorder. Neurochemistry International, 142, 104921. https://doi.org/10.1016/j.neuint.2020.104921
Eraly, S. A., Nievergelt, C. M., Maihofer, A. X., Barkauskas, D. A., Biswas, N., Agorastos, A., O’Connor, D. T.; Baker, D. G.. (2014). Assessment of plasma C-reactive protein as a biomarker of posttraumatic stress disorder risk. JAMA Psychiatry, 71, 423-431. https://doi.org/10.1001/jamapsychiatry.2013.4374
Figge, D. A., & Standaert, D. G. (2017). Dysregulation of BET proteins in levodopa-induced dyskinesia. Neurobiology of Diseases, 102, 125-132. https://doi.org/10.1016/j.nbd.2017.03.003
Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., Philpott, M., Munro, S., McKeown, M. R., Wang, Y., Christie, A. L., West, N., Cameron, M. J., Schwartz, B., Heightman, T. D., … Bradner, J. E. (2010). Selective inhibition of BET bromodomains. Nature, 468, 1067-1073. https://doi.org/10.1038/nature09504
Gallo, F. T., Katche, C., Morici, J. F., Medina, J. H., & Weisstaub, N. V. (2018). Immediate early genes, memory and psychiatric disorders: focus on c-Fos, Egr1 and Arc. Frontiers in Behavioral Neuroscience, 12, 79..https://doi.org/10.3389/fnbeh.2018.00079
Guo, W., Long, H., Bu, Q., Zhao, Y., Wang, H., Tian, J., & Cen, X. (2020). Role of BRD4 phosphorylation in the nucleus accumbens in relapse to cocaine-seeking behavior in mice. Addiction Biology, 25, e12808. https://doi.org/10.1111/adb.12808
Han, Y., Tao, C., Gao, X., Wang, L., Jiang, F., Wang, C., Fang, K., Chen, X., Chen, Z., & Ge, J. (2018). BDNF-related imbalance of copine 6 and synaptic plasticity markers couples with depression-like behavior and immune activation in CUMS rats. Frontiers in Neuroscience, 12, 731. https://doi.org/10.3389/fnins.2018.00731
He, M., Wei, J.-X., Mao, M., Zhao, G.-Y., Tang, J.-J., Feng, S., Lu, X.-M., & Wang, Y.-T. (2018). Synaptic plasticity in PTSD and associated comorbidities: the function and mechanism for diagnostics and therapy. Current Pharmaceutical Design, 24, 4051-4059. https://doi.org/10.2174/1381612824666181120094749
Henry, C. J., Huang, Y., Wynne, A., Hanke, M., Himler, J., Bailey, M. T., Sheridan, J. F., & Godbout, J. P. (2008). Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia. Journal of Neuroinflammation, 5, 15. https://doi.org/10.1186/1742-2094-5-15
Hoogland, I. C. M., Houbolt, C., van Westerloo, D. J., van Gool, W. A., & van de Beek, D. (2015). Systemic inflammation and microglial activation: systematic review of animal experiments. Journal of Neuroinflammation, 12, 114. https://doi.org/10.1186/s12974-015-0332-6
Hori, H., & Kim, Y. (2019). Inflammation and post-traumatic stress disorder. Psychiatry and Clinical Neurosciences, 73, 143-153. https://doi.org/10.1111/pcn.12820
Huang, B., Yang, X.-D., Zhou, M.-M., Ozato, K., & Chen, L.-F. (2009). Brd4 coactivates transcriptional activation of NF-κB via specific binding to acetylated RelA. Molecular and Cellular Biology, 29, 1375-1387. https://doi.org/10.1128/MCB.01365-08
Jiang, Y., Zhu, L., Zhang, T., Lu, H., Wang, C., Xue, B., Xu, X., Liu, Y. U., Cai, Z., Sang, W., Hua, Y., & Ma, J. (2017). BRD4 has dual effects on the HMGB1 and NF-κB signalling pathways and is a potential therapeutic target for osteoarthritis. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1863, 3001-3015. https://doi.org/10.1016/j.bbadis.2017.08.009
Känel, R. V., Hepp, U., Kraemer, B., Traber, R., Keel, M., Mica, L., & Schnyder, U. (2007). Evidence for low-grade systemic proinflammatory activity in patients with posttraumatic stress disorder. Journal of Psychiatric Research, 41, 744-752. https://doi.org/10.1016/j.jpsychires.2006.06.009
Kim, Y.-K., Amidfar, M., & Won, E. (2018). A review on inflammatory cytokine-induced alterations of the brain as potential neural biomarkers in post-traumatic stress disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 91, 103-112. https://doi.org/10.1016/j.pnpbp.2018.06.008
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., Aguilar-Gaxiola, S., Al-Hamzawi, A., Alonso, J., Bunting, B., Ciutan, M., de Girolamo, G., … Kessler, R. C. (2017). Posttraumatic stress disorder in the World Mental Health Surveys. Psychological Medicine, 47, 2260-2274. https://doi.org/10.1017/S0033291717000708
Korb, E., Herre, M., Zucker-Scharff, I., Darnell, R. B., & Allis, C. D. (2015). BET protein Brd4 activates transcription in neurons and BET inhibitor Jq1 blocks memory in mice. Nature Neuroscience, 18, 1464-1473. https://doi.org/10.1038/nn.4095
Korb, E., Herre, M., Zucker-Scharff, I., Gresack, J., Allis, C. D., & Darnell, R. B. (2017). Excess translation of epigenetic regulators contributes to Fragile X syndrome and is alleviated by Brd4 inhibition. Cell, 170, 1209-1223.e20. https://doi.org/10.1016/j.cell.2017.07.033
Krystal, J. H., Davis, L. L., Neylan, T. C., A. Raskind, M., Schnurr, P. P., Stein, M. B., Vessicchio, J., Shiner, B., Gleason, T. D., & Huang, G. D. (2017). It is time to address the crisis in the pharmacotherapy of posttraumatic stress disorder: a consensus statement of the PTSD Psychopharmacology Working Group. Biological Psychiatry, 82, e51-e59. https://doi.org/10.1016/j.biopsych.2017.03.007
Kunimatsu, A., Yasaka, K., Akai, H., Kunimatsu, N., & Abe, O. (2020). MRI findings in posttraumatic stress disorder. Journal of Magnetic Resonance Imaging, 52, 380-396. https://doi.org/10.1002/jmri.26929
Le, Y., Liu, S., Peng, M., Tan, C., Liao, Q., Duan, K., Ouyang, W., & Tong, J. (2014). Aging differentially affects the loss of neuronal dendritic spine, neuroinflammation and memory impairment at rats after surgery. PLoS One, 9, e106837. https://doi.org/10.1371/journal.pone.0106837
Levin, S. G., & Godukhin, O. V. (2017). Modulating effect of cytokines on mechanisms of synaptic plasticity in the brain. Biochemistry (Moscow), 82, 264-274. https://doi.org/10.1134/S000629791703004X
Levkovitz, Y., Fenchel, D., Kaplan, Z., Zohar, J., & Cohen, H. (2015). Early post-stressor intervention with minocycline, a second-generation tetracycline, attenuates post-traumatic stress response in an animal model of PTSD. European Neuropsychopharmacology, 25, 124-132. https://doi.org/10.1016/j.euroneuro.2014.11.012
Li, F., Xiang, H., Lu, J., Chen, Z., Huang, C., & Yuan, X. (2020). Lycopene ameliorates PTSD-like behaviors in mice and rebalances the neuroinflammatory response and oxidative stress in the brain. Physiology & Behavior, 224, 113026. https://doi.org/10.1016/j.physbeh.2020.113026
Li, S., Liao, Y., Dong, Y., Li, X., Li, J., Cheng, Y., Cheng, J., & Yuan, Z. (2021). Microglial deletion and inhibition alleviate behavior of post-traumatic stress disorder in mice. Journal of Neuroinflammation, 18, 7. https://doi.org/10.1186/s12974-020-02069-9
Liang, E., Ma, M., Wang, L., Liu, X., Xu, J., Zhang, M., Yang, R., & Zhao, Y. (2018). The BET/BRD inhibitor JQ1 attenuates diabetes-induced cognitive impairment in rats by targeting Nox4-Nrf2 redox imbalance. Biochemical and Biophysical Research Communications, 495, 204-211. https://doi.org/10.1016/j.bbrc.2017.11.020
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods, 25, 402-408. https://doi.org/10.1006/meth.2001.1262
Machida, M., Lonart, G., & Sanford, L. D. (2018). Effects of stressor controllability on transcriptional levels of c-fos, Arc, and brain-derived neurotrophic factor in mouse amygdala and medial prefrontal cortex. NeuroReport, 29, 112-117. https://doi.org/10.1097/WNR.0000000000000919
Meissner, A., Visanji, N. P., Momen, M. A., Feng, R., Francis, B. M., Bolz, S.-S., & Hazrati, L.-N. (2015). Tumor necrosis factor-α underlies loss of cortical dendritic spine density in a mouse model of congestive heart failure. Journal of the American Heart Association, 4(5), e001920. https://doi.org/10.1161/JAHA.115.001920
Meng, S., Zhang, L., Tang, Y., Tu, Q., Zheng, L., Yu, L., Murray, D., Cheng, J., Kim, S. H., Zhou, X., & Chen, J. (2014). BET inhibitor JQ1 blocks inflammation and bone destruction. Journal of Dental Research, 93, 657-662. https://doi.org/10.1177/0022034514534261
Michopoulos, V., Powers, A., Gillespie, C. F., Ressler, K. J., & Jovanovic, T. (2017). Inflammation in fear- and anxiety-based disorders: PTSD, GAD, and beyond. Neuropsychopharmacology, 42, 254-270. https://doi.org/10.1038/npp.2016.146
Minatohara, K., Akiyoshi, M., & Okuno, H. (2016). Role of immediate-early genes in synaptic plasticity and neuronal ensembles underlying the memory trace. Frontiers in Molecular Neuroscience, 8, 78. https://doi.org/10.3389/fnmol.2015.00078
Nalloor, R., Bunting, K. M., & Vazdarjanova, A. (2014). Altered hippocampal function before emotional trauma in rats susceptible to PTSD-like behaviors. Neurobiology of Learning and Memory, 112, 158-167. https://doi.org/10.1016/j.nlm.2014.02.006
Nikolaienko, O., Patil, S., Eriksen, M. S., & Bramham, C. R. (2018). Arc protein: A flexible hub for synaptic plasticity and cognition. Seminars in Cell & Developmental Biology, 77, 33-42. https://doi.org/10.1016/j.semcdb.2017.09.006
Okada, R., Matsumoto, K., Tsushima, R., Fujiwara, H., & Tsuneyama, K. (2014). Social isolation stress-induced fear memory deficit is mediated by down-regulated neuro-signaling system and Egr-1 expression in the brain. Neurochemical Research, 39, 875-882. https://doi.org/10.1007/s11064-014-1283-5
Ons, S., Rotllant, D., Marín-Blasco, I. J., & Armario, A. (2010). Immediate-early gene response to repeated immobilization: Fos protein and arc mRNA levels appear to be less sensitive than c-fos mRNA to adaptation. European Journal of Neuroscience, 31, 2043-2052. https://doi.org/10.1111/j.1460-9568.2010.07242.x
Ploski, J. E., Pierre, V. J., Smucny, J., Park, K., Monsey, M. S., Overeem, K. A., & Schafe, G. E. (2008). The activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) is required for memory consolidation of pavlovian fear conditioning in the lateral amygdala. Journal of Neuroscience, 28, 12383-12395. https://doi.org/10.1523/JNEUROSCI.1662-08.2008
Prut, L., & Belzung, C. (2003). The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: A review. European Journal of Pharmacology, 463, 3-33. https://doi.org/10.1016/S0014-2999(03)01272-X
Rosen, J. B., Fanselow, M. S., Young, S. L., Sitcoske, M., & Maren, S. (1998). Immediate-early gene expression in the amygdala following footshock stress and contextual fear conditioning. Brain Research, 796, 132-142. https://doi.org/10.1016/S0006-8993(98)00294-7
Rudman, M. D., Choi, J. S., Lee, H. E., Tan, S. K., Ayad, N. G., & Lee, J. K. (2018). Bromodomain and extraterminal domain-containing protein inhibition attenuates acute inflammation after spinal cord injury. Experimental Neurology, 309, 181-192. https://doi.org/10.1016/j.expneurol.2018.08.005
Runge, K., Cardoso, C., & de Chevigny, A. (2020). Dendritic spine plasticity: Function and mechanisms. Frontiers in Synaptic Neuroscience, 12,36. https://doi.org/10.3389/fnsyn.2020.00036
Sánchez-Ventura, J., Amo-Aparicio, J., Navarro, X., & Penas, C. (2019). BET protein inhibition regulates cytokine production and promotes neuroprotection after spinal cord injury. Journal of Neuroinflammation, 16, 124. https://doi.org/10.1186/s12974-019-1511-7
Shalev, A., Liberzon, I., & Marmar, C. (2017). Post-traumatic stress disorder. New England Journal of Medicine, 376, 2459-2469. https://doi.org/10.1056/NEJMra1612499
Singh, M. B., & Sartor, G. C. (2020). BET bromodomains as novel epigenetic targets for brain health and disease. Neuropharmacology, 181, 108306. https://doi.org/10.1016/j.neuropharm.2020.108306
Smith, K. L., Kassem, M. S., Clarke, D. J., Kuligowski, M. P., Bedoya-Pérez, M. A., Todd, S. M., Lagopoulos, J., Bennett, M. R., & Arnold, J. C. (2019). Microglial cell hyper-ramification and neuronal dendritic spine loss in the hippocampus and medial prefrontal cortex in a mouse model of PTSD. Brain, Behavior, and Immunity, 80, 889-899. https://doi.org/10.1016/j.bbi.2019.05.042
Speer, K., Upton, D., Semple, S., & McKune, A. (2018). Systemic low-grade inflammation in post-traumatic stress disorder: A systematic review. Journal of Inflammation Research, 11, 111-121. https://doi.org/10.2147/JIR.S155903
Spencer, S. J., D’Angelo, H., Soch, A., Watkins, L. R., Maier, S. F., & Barrientos, R. M. (2017). High-fat diet and aging interact to produce neuroinflammation and impair hippocampal- and amygdalar-dependent memory. Neurobiology of Aging, 58, 88-101. https://doi.org/10.1016/j.neurobiolaging.2017.06.014
Sun, L., Zhang, H., Wang, W., Chen, Z., Wang, S., Li, J., Li, G., Gao, C., & Sun, X. (2020). Astragaloside IV exerts cognitive benefits and promotes hippocampal neurogenesis in stroke mice by downregulating interleukin-17 expression via Wnt pathway. Frontiers in Pharmacology, 11, 111. https://doi.org/10.3389/fphar.2020.00421
Tucker, P., Ruwe, W. D., Masters, B., Parker, D. E., Hossain, A., Trautman, R. P., & Wyatt, D. B. (2004). Neuroimmune and cortisol changes in selective serotonin reuptake inhibitor and placebo treatment of chronic posttraumatic stress disorder. Biological Psychiatry, 56, 121-128. https://doi.org/10.1016/j.biopsych.2004.03.009
Verbitsky, A., Dopfel, D., & Zhang, N. (2020). Rodent models of post-traumatic stress disorder: Behavioral assessment. Translational Psychiatry, 10, 1-28. https://doi.org/10.1038/s41398-020-0806-x
Wang, H., Huang, W., Liang, M., Shi, Y., Zhang, C., Li, Q., Liu, M., Shou, Y., Yin, H., Zhu, X., Sun, X., Hu, Y. U., & Shen, Z. (2018). (+)-JQ1 attenuated LPS-induced microglial inflammation via MAPK/NFκB signaling. Cell & Bioscience, 8, 60. https://doi.org/10.1186/s13578-018-0258-7
Wang, J., Chen, J., Jin, H., Lin, D., Chen, Y. U., Chen, X., Wang, B., Hu, S., Wu, Y., Wu, Y., Zhou, Y., Tian, N., Gao, W., Wang, X., & Zhang, X. (2019). BRD4 inhibition attenuates inflammatory response in microglia and facilitates recovery after spinal cord injury in rats. Journal of Cellular and Molecular Medicine, 23, 3214-3223. https://doi.org/10.1111/jcmm.14196
Wang, J., Hu, J., Chen, X., Huang, C., Lin, J., Shao, Z., Gu, M., Wu, Y., Tian, N., Gao, W., Zhou, Y., Wang, X., & Zhang, X. (2019). BRD4 inhibition regulates MAPK, NF-κB signals, and autophagy to suppress MMP-13 expression in diabetic intervertebral disc degeneration. The FASEB Journal, 33, 11555-11566. https://doi.org/10.1096/fj.201900703R
Wang, J., Zhou, F., Li, Z., Mei, H., Wang, Y. E., Ma, H., Shi, L., Huang, A. I., Zhang, T., Lin, Z., & Wu, G. (2018). Pharmacological targeting of BET proteins attenuates radiation-induced lung fibrosis. Scientific Reports, 8, 998. https://doi.org/10.1038/s41598-018-19343-9
Wang, R., Wang, W., Xu, J., Liu, D., Wu, H., Qin, X., Jiang, H., & Pan, F. (2020). Jmjd3 is involved in the susceptibility to depression induced by maternal separation via enhancing the neuroinflammation in the prefrontal cortex and hippocampus of male rats. Experimental Neurology, 328, 113254. https://doi.org/10.1016/j.expneurol.2020.113254
Wang, S.-C., Lin, C.-C., Chen, C.-C., Tzeng, N.-S., & Liu, Y.-P. (2018). Effects of oxytocin on fear memory and neuroinflammation in a rodent model of posttraumatic stress disorder. International Journal of Molecular Sciences, 19(12), 3848. https://doi.org/10.3390/ijms19123848
Wang, W., Wang, R., Xu, J., Qin, X., Jiang, H., Khalid, A., Liu, D., Pan, F., Ho, C. S. H., & Ho, R. C. M. (2018). Minocycline attenuates stress-induced behavioral changes via its anti-inflammatory effects in an animal model of post-traumatic stress disorder. Frontiers in Psychiatry, 9, 558. https://doi.org/10.3389/fpsyt.2018.00558
Wang, Y., Zhu, T., Wang, M., Zhang, F., Zhang, G., Zhao, J., Zhang, Y., Wu, E., & Li, X. (2019). Icariin attenuates M1 activation of microglia and Aβ plaque accumulation in the hippocampus and prefrontal cortex by up-regulating PPARγ in restraint/isolation-stressed APP/PS1 mice. Frontiers in Neuroscience, 13, 291. https://doi.org/10.3389/fnins.2019.00291
Willner, P., Towell, A., Sampson, D., Sophokleous, S., & Muscat, R. (1987). Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology, 93, 358-364. https://doi.org/10.1007/BF00187257
Xu, Y., Pan, J., Sun, J., Ding, L., Ruan, L., Reed, M., Yu, X., klabnik, J., Lin, D., Li, J., Chen, L., Zhang, C., Zhang, H., & O'Donnell, J. M. (2015). Inhibition of phosphodiesterase 2 reverses impaired cognition and neuronal remodeling caused by chronic stress. Neurobiology of Aging, 36, 955-970. https://doi.org/10.1016/j.neurobiolaging.2014.08.028
Yoon, S., & Kim, Y.-K. (2019). Neuroendocrinological treatment targets for posttraumatic stress disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 90, 212-222. https://doi.org/10.1016/j.pnpbp.2018.11.021
Zhao, M., Wang, W., Jiang, Z., Zhu, Z., Liu, D., & Pan, F. (2020). Long-term effect of post-traumatic stress in adolescence on dendrite development and H3K9me2/BDNF expression in male rat hippocampus and prefrontal cortex. Frontiers in Cell and Developmental Biology, 8, 682. https://doi.org/10.3389/fcell.2020.00682
Zhou, Y., Gu, Y., & Liu, J. (2019). BRD4 suppression alleviates cerebral ischemia-induced brain injury by blocking glial activation via the inhibition of inflammatory response and pyroptosis. Biochemical and Biophysical Research Communications, 519, 481-488. https://doi.org/10.1016/j.bbrc.2019.07.097