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Original Research | Open Access

Compound B vitamins mitigate post-traumatic stress disorder-like behaviors induced by single prolonged stress in rats by inhibiting hippocampal mitochondrial DNA methylation

Yanteng Lia,b, Runzi Wangc, Fang Xied, Lingjia Qiand( ), Yong Zhangc( ), Jianning Zhanga,b( )
Senior Department of Neurosurgery, the First Medical Center of PLA General Hospital, Beijing 100853, China
PLA Medical School, Beijing 100853, China
Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Institute of Exercise and Health, Tianjin University of Sport, Tianjin 301901, China
Department of Military Cognition and Stress Medicine, Institute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing 100039, China
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Abstract

Background

Post-traumatic stress disorder (PTSD) is a serious mental disorder. Current treatments, typically using serotonin reuptake inhibitors, have limited effectiveness and often cause severe adverse effects. In the present study, we investigated whether Compound B vitamins (VBco) have protective effects in improving PTSD-like behaviors and the possible related molecular mechanisms in a rat model of single prolonged stress (SPS).

Methods

Eighty adult male rats were randomly divided into four groups (n = 20): control (CTRL), SPS, VBco control (CTRL-VBco), and SPS and VBco (SPS-VBco). After modeling, behavioral tests (including open field test, forced swimming test, sucrose preference test, fear conditioning test) were conducted. Blood was collected to detect plasma homocysteine (Hcy) concentrations. Brain tissue was collected for mitochondrial function analysis, western blotting, and quantitative real-time Polymerase Chain Reaction (PCR).

Results

VBco reduced plasma Hcy levels significantly 1 week post-SPS. The SPS-VBco group showed decreased grooming times and increased movement speed in the open field test, less resting time in the forced swim test, increased sucrose preference ratios in the sucrose preference test, and less freezing time in the fear conditioning test. VBco increased the expression of mRNA for subunits of respiratory chain-related protein in hippocampal mitochondria and improved mitochondrial complex Ⅰ and Ⅳ activity and membrane potential in hippocampus. VBco reversed SPS-induced mtND1 and mtND3 methylation in hippocampal mitochondria. VBco downregulated the levels of methyltransferases (DNMT1, DNMT3A, DNMT3B) in hippocampal mitochondria.

Conclusion

VBco can inhibit hippocampal mitochondrial DNA methylation effectively. This may be one of the mechanisms by which it attenuates PTSD-like behaviors.

Keywords

DNA methylationPost-traumatic stress disorderCompound B vitaminsHippocampusMitochondriaSingle prolonged stress

References

1

Ostacher MJ, Cifu AS. Management of posttraumatic stress disorder. JAMA. 2019;321(2):200–201. https://doi.org/10.1001/jama.2018.19290.
Crossref Google Scholar
2

Lang AJ, Hamblen JL, Holtzheimer P, et al. A clinician's guide to the 2023 VA/DoD clinical practice guideline for management of posttraumatic stress disorder and acute stress disorder. J Trauma Stress. 2024;37(1):19–34. https://doi.org/10.1002/jts.23013.
Crossref Google Scholar
3

Ressler KJ, Berretta S, Bolshakov VY, et al. Post-traumatic stress disorder: clinical and translational neuroscience from cells to circuits. Nat Rev Neurol. 2022;18(5):273–288. https://doi.org/10.1038/s41582-022-00635-8.
Crossref Google Scholar
4

Song Y, Cao H, Zuo CC, et al. Mitochondrial dysfunction: a fatal blow in depression. Biomed Pharmacother. 2023;167:115652. https://doi.org/10.1016/j.biopha.2023.115652.
Crossref Google Scholar
5

Kaplan GB, Dadhi NA, Whitaker CS. Mitochondrial dysfunction in animal models of PTSD: relationships between behavioral models, neural regions, and cellular maladaptation. Front Physiol. 2023;14:1105839. https://doi.org/10.3389/fphys.2023.1105839.
Crossref Google Scholar
6

Ali NH, Al-Kuraishy HM, Al-Gareeb AI, et al. Role of brain renin-angiotensin system in depression: a new perspective. CNS Neurosci Ther. 2024;30(4):e14525. https://doi.org/10.1111/cns.14525.
Crossref Google Scholar
7

Geng HX, An QH, Song J, et al. Cadmium-induced global DNA hypermethylation promoting mitochondrial dynamics dysregulation in hippocampal neurons. Environ Toxicol. 2024;39(4):2043–2051. https://doi.org/10.1002/tox.24083.
Crossref Google Scholar
8

Kim H, Kim G, Jang W, et al. Association between intake of B vitamins and cognitive function in elderly Koreans with cognitive impairment. Nutr J. 2014;13(1):118. https://doi.org/10.1186/1475-2891-13-118.
Crossref Google Scholar
9

Rosenberg IH. Vitamin B12 and age-related cognitive decline-dementia and “alzheimer's disease”. Food Nutr Bull. 2024;45(1_suppl l):S50–S52. https://doi.org/10.1177/03795721241228060.
Crossref Google Scholar
10

Al-Kuraishy HM, Abdulhadi MH, Hussien NR, et al. Involvement of orexinergic system in psychiatric and neurodegenerative disorders: a scoping review. Brain Circ. 2020;6(2):70–80. https://doi.org/10.4103/bc.bc_42_19.
Crossref Google Scholar
11

Al-Kuraishy HM, Al-Gareeb AI, Alexiou A, et al. New insights on the potential effect of orexin receptor antagonist suvorexant on Parkinson's disease symptoms. Neurol Sci. 2024;45(5):2367–2368. https://doi.org/10.1007/s10072-023-07261-2.
Crossref Google Scholar
12

Ling YT, Yuan SQ, Huang XX, et al. Associations of folate/folic acid supplementation alone and in combination with other B vitamins on dementia risk and brain structure: evidence from 466224 UK biobank participants. J Gerontol A Biol Sci Med Sci. 2024;79(4):glad266. https://doi.org/10.1093/gerona/glad266.
Crossref Google Scholar
13

Smith AD, Refsum H. Homocysteine, B vitamins, and cognitive impairment. Annu Rev Nutr. 2016;36:211–239. https://doi.org/10.1146/annurev-nutr-071715-050947.
Crossref Google Scholar
14

Wang SD, Wang X, Zhao Y, et al. Homocysteine-induced disturbances in DNA methylation contribute to development of stress-associated cognitive decline in rats. Neurosci Bull. 2022;38(8):887–900. https://doi.org/10.1007/s12264-022-00852-7.
Crossref Google Scholar
15

Lisieski MJ, Eagle AL, Conti AC, et al. Single-prolonged stress: a review of two decades of progress in a rodent model of post-traumatic stress disorder. Front Psychiatr. 2018;9:196. https://doi.org/10.3389/fpsyt.2018.00196.
Crossref Google Scholar
16

Kong CH, Park K, Kim DY, et al. Effects of oleanolic acid and ursolic acid on depression-like behaviors induced by maternal separation in mice. Eur J Pharmacol. 2023;956:175954. https://doi.org/10.1016/j.ejphar.2023.175954.
Crossref Google Scholar
17

Li TQ, Steibel JP, Willette AA. Vitamin B6, B12, and folate's influence on neural networks in the UK biobank cohort. Nutrients. 2024;16(13):2050. https://doi.org/10.3390/nu16132050.
Crossref Google Scholar
18

Ramamoorthy K, Yoshimura R, Al-Juburi S, et al. Alzheimer's disease is associated with disruption in thiamin transport physiology: a potential role for neuroinflammation. Neurobiol Dis. 2022;171:105799. https://doi.org/10.1016/j.nbd.2022.105799.
Crossref Google Scholar
19

Huang H, Zheng SY, Chen M, et al. The potential of the P2X7 receptor as a therapeutic target in a sub-chronic PCP-induced rodent model of schizophrenia. J Chem Neuroanat. 2021;116:101993. https://doi.org/10.1016/j.jchemneu.2021.101993.
Crossref Google Scholar
20

Imeni Kashan A, Mirzaasgari Z, Nouri Shirazi S. Relationship between serum levels of folic acid and homocysteine with cognitive impairment in patients diagnosed with multiple sclerosis. Medicine. 2024;103(28):e38680. https://doi.org/10.1097/MD.0000000000038680.
Crossref Google Scholar
21

Śliwiński W, Gawlik-Kotelnicka O. Circulating B vitamins metabolites in depressive disorders - connections with the microbiota-gut-brain axis. Behav Brain Res. 2024;472:115145. https://doi.org/10.1016/j.bbr.2024.115145.
Crossref Google Scholar
22

Rowe K, Bröcker E, Suliman S, et al. The relationship between nutrient intake and executive function in adults with post-traumatic stress disorder. J Affect Disord. 2024;349:125–131. https://doi.org/10.1016/j.jad.2024.01.065.
Crossref Google Scholar
23

Souza RR, Noble LJ, McIntyre CK. Using the single prolonged stress model to examine the pathophysiology of PTSD. Front Pharmacol. 2017;8:615. https://doi.org/10.3389/fphar.2017.00615.
Crossref Google Scholar
24

McCaddon A, Miller JW. Homocysteine-a retrospective and prospective appraisal. Front Nutr. 2023;10:1179807. https://doi.org/10.3389/fnut.2023.1179807.
Crossref Google Scholar
25

Prajjwal P, Asharaf S, Makhanasa D, et al. Association of Alzheimer's dementia with oral bacteria, vitamin B12, folate, homocysteine levels, and insulin resistance along with its pathophysiology, genetics, imaging, and biomarkers. Dis Mon. 2023;69(5):101546. https://doi.org/10.1016/j.disamonth.2023.101546.
Crossref Google Scholar
26

Jendricko T, Vidović A, Grubisić-Ilić M, et al. Homocysteine and serum lipids concentration in male war veterans with posttraumatic stress disorder. Prog Neuro-Psychopharmacol Biol Psychiatry. 2009;33(1):134–140. https://doi.org/10.1016/j.pnpbp.2008.11.002.
Crossref Google Scholar
27

Yang LD, Xing WL, Shi Y, et al. Stress-induced NLRP3 inflammasome activation and myelin alterations in the hippocampus of PTSD rats. Neuroscience. 2024;555:156–166. https://doi.org/10.1016/j.neuroscience.2024.07.028.
Crossref Google Scholar
28

Van der Watt ASJ, Plessis SD, Ahmed F, et al. Hippocampus, amygdala, and Insula activation in response to romantic relationship dissolution stimuli: a case-case-control fMRI study on emerging adult students. J Affect Disord. 2024;356:604–615. https://doi.org/10.1016/j.jad.2024.04.059.
Crossref Google Scholar
29

Ben-Zion Z, Korem N, Fine NB, et al. Structural neuroimaging of hippocampus and amygdala subregions in posttraumatic stress disorder: a scoping review. Biol Psychiatry Glob Open Sci. 2023;4(1):120–134. https://doi.org/10.1016/j.bpsgos.2023.07.001.
Crossref Google Scholar
30

Kmita H, Pinna G, Lushchak VI. Potential oxidative stress related targets of mitochondria-focused therapy of PTSD. Front Physiol. 2023;14:1266575. https://doi.org/10.3389/fphys.2023.1266575.
Crossref Google Scholar
31

Zhang L, Li H, Hu X, et al. Mitochondria-focused gene expression profile reveals common pathways and CPT1B dysregulation in both rodent stress model and human subjects with PTSD. Transl Psychiatry. 2015;5(6):e580. https://doi.org/10.1038/tp.2015.65.
Crossref Google Scholar
32

Lushchak O, Strilbytska O, Koliada A, et al. An orchestrating role of mitochondria in the origin and development of post-traumatic stress disorder. Front Physiol. 2022;13:1094076. https://doi.org/10.3389/fphys.2022.1094076.
Crossref Google Scholar
33

Bahabry R, Hauser RM, Sánchez RG, et al. Alterations in DNA 5-hydroxymethylation patterns in the hippocampus of an experimental model of chronic epilepsy. Neurobiol Dis. 2024;200:106638. https://doi.org/10.1016/j.nbd.2024.106638.
Crossref Google Scholar
34

Park C, Rosenblat JD, Brietzke E, et al. Stress, epigenetics and depression: a systematic review. Neurosci Biobehav Rev. 2019;102:139–152. https://doi.org/10.1016/j.neubiorev.2019.04.010.
Crossref Google Scholar
35

Wheater ENW, Stoye DQ, Cox SR, et al. DNA methylation and brain structure and function across the life course: a systematic review. Neurosci Biobehav Rev. 2020;113:133–156. https://doi.org/10.1016/j.neubiorev.2020.03.007.
Crossref Google Scholar
36

Fujikawa R, Ramsaran AI, Guskjolen A, et al. Neurogenesis-dependent remodeling of hippocampal circuits reduces PTSD-like behaviors in adult mice. Mol Psychiatr. 2024;29(11):3316–3329. https://doi.org/10.1038/s41380-024-02585-7.
Crossref Google Scholar
37

Du J, Zhu M, Bao HK, et al. The role of nutrients in protecting mitochondrial function and neurotransmitter signaling: implications for the treatment of depression, PTSD, and suicidal behaviors. Crit Rev Food Sci Nutr. 2016;56(15):2560–2578. https://doi.org/10.1080/10408398.2013.876960.
Crossref Google Scholar
Journal of Neurorestoratology
Volume 13 Issue 2,
April 2025
DOI: 10.1016/j.jnrt.2025.100187
Cite this article:
Li Y, Wang R, Xie F, et al. Compound B vitamins mitigate post-traumatic stress disorder-like behaviors induced by single prolonged stress in rats by inhibiting hippocampal mitochondrial DNA methylation. Journal of Neurorestoratology, 2025, 13(2). https://doi.org/10.1016/j.jnrt.2025.100187

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Received: 21 August 2024
Revised: 17 November 2024
Accepted: 04 December 2024
Published: 01 April 2025
© 2025

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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