Role mechanism of the postsynaptic scaffold protein Preso in the induction of post-traumatic stress disorder by blast traumatic brain injury

CAO Zixuan; ZHANG Zhuoyuan; LIU Dan; LI Tianjing; LIAO Dan; ZHANG Min; GE Junmiao; LUO Peng; LI Xin

doi:10.11883/bzycj-2024-0216

Article Contents

Article Navigation > Explosion And Shock Waves > 2024 > Accepted Manuscript

CAO Zixuan, ZHANG Zhuoyuan, LIU Dan, LI Tianjing, LIAO Dan, ZHANG Min, GE Junmiao, LUO Peng, LI Xin. Role mechanism of the postsynaptic scaffold protein Preso in the induction of post-traumatic stress disorder by blast traumatic brain injury[J]. Explosion And Shock Waves. doi: 10.11883/bzycj-2024-0216

Citation:

CAO Zixuan, ZHANG Zhuoyuan, LIU Dan, LI Tianjing, LIAO Dan, ZHANG Min, GE Junmiao, LUO Peng, LI Xin. Role mechanism of the postsynaptic scaffold protein Preso in the induction of post-traumatic stress disorder by blast traumatic brain injury[J]. Explosion And Shock Waves. doi: 10.11883/bzycj-2024-0216

Citation:

CAO Zixuan, ZHANG Zhuoyuan, LIU Dan, LI Tianjing, LIAO Dan, ZHANG Min, GE Junmiao, LUO Peng, LI Xin. Role mechanism of the postsynaptic scaffold protein Preso in the induction of post-traumatic stress disorder by blast traumatic brain injury[J]. Explosion And Shock Waves. doi: 10.11883/bzycj-2024-0216

PDF( 1925 KB)

Role mechanism of the postsynaptic scaffold protein Preso in the induction of post-traumatic stress disorder by blast traumatic brain injury

doi: 10.11883/bzycj-2024-0216

CAO Zixuan^{1, 2
,},
ZHANG Zhuoyuan^{1, 3},
LIU Dan^{1, 3},
LI Tianjing^{1, 3},
LIAO Dan¹,
ZHANG Min¹,
GE Junmiao¹,
LUO Peng¹,
LI Xin^{1
,
,}

1.
Xijing Hospital, Air Force Medical University, Xiʼan 710032, Shaanxi, China
2.
School of Basic Medicine, Air Force Medical University, Xiʼan 710032, Shaanxi, China
3.
College of Life Sciences, Northwest University, Xiʼan 710069, Shaanxi, China

Received Date: 2024-07-01
Rev Recd Date: 2025-05-12

Available Online: 2024-10-24

Abstract

Abstract

To investigate the mechanism of post-synaptic scaffold protein Preso in the exacerbation of post-traumatic stress disorder (PTSD) by blast-related traumatic brain injury (bTBI), thirty-six male C57 mice were randomly divided into the control group (Sham group), 3.5 MPa bTBI group, 4.5 MPa bTBI group, 5.5 MPa bTBI group, 4.5 MPa bTBI+saline group, 4.5 MPa bTBI+small molecule interfering peptide (TAT-FERM) group, and 6 mice in each group. And twelve Preso^-/- mice were randomly divided into Sham group and 4.5 MPa bTBI group, with 6 mice in each group. The mice were subjected to bTBI modelling and were routinely kept for 2 weeks after completion. 4.5 MPa bTBI+saline group and 4.5 MPa bTBI+TAT-FERM group were administered once a day through the tail vein for 5 consecutive days after bTBI modelling. Compared with the control group, the anxiety and depression behavior of 3.5 MPa bTBI mice was not significantly changed. Mice in the 4.5 MPa bTBI and 5.5 MPa bTBI groups showed significant PTSD symptoms and promoted the formation of the Preso/mGluR1 complex. The use of TAT-FERM blocked the interaction between Preso and mGluR1, inhibited the formation of Preso/mGluR1 complex without altering the expression of Preso/mGluR1 complex component proteins, and ameliorated PTSD symptoms caused by bTBI. Results display that the promotion of Preso/mGluR1 complex formation by bTBI is an important molecular pathological mechanism by which bTBI induces PTSD symptoms. The effect of bTBI on PTSD can be attenuated by blocking the interaction between Preso and mGluR1, providing a potential target for the treatment of bTBI-associated PTSD.
- blast traumatic brain injury,
- post-traumatic stress disorder,
- postsynaptic scaffolding proteins,
- metabotropic glutamate receptors,
- small molecule peptides

FullText(HTML)

References(13)

References

[1]	LINDBERG M A, MOY MARTIN E M, MARION D W. Military traumatic brain injury: the history, impact, and future [J]. Journal of Neurotrauma, 2022, 39(17/18): 1133–1145. DOI: 10.1089/neu.2022.0103.
[2]	TROYANSKAYA M, PASTOREK N J, SCHEIBEL R S, et al. Combat exposure, PTSD symptoms, and cognition following blast-related traumatic brain injury in OEF/OIF/OND service members and veterans [J]. Military Medicine, 2015, 180(3): 285–289. DOI: 10.7205/MILMED-D-14-00256.
[3]	KAPLAN G B, LEITE-MORRIS K A, WANG L, et al. Pathophysiological bases of comorbidity: traumatic brain injury and post-traumatic stress disorder [J]. Journal of Neurotrauma, 2018, 35(2): 210–225. DOI: 10.1089/neu.2016.4953.
[4]	JAMJOOM A A B, RHODES J, ANDREWS P J D, et al. The synapse in traumatic brain injury [J]. Brain, 2021, 144(1): 18–31. DOI: 10.1093/brain/awaa321.
[5]	HU J H, YANG L L, KAMMERMEIER P J, et al. Preso1 dynamically regulates group I metabotropic glutamate receptors [J]. Nature Neuroscience, 2012, 15(6): 836–844. DOI: 10.1038/nn.3103.
[6]	ZHANG Z Y, GAO X Y, TIAN Z C, et al. Preso enhances mGluR1-mediated excitotoxicity by modulating the phosphorylation of mGluR1-Homer1 complex and facilitating an ER stress after traumatic brain injury [J]. Cell Death Discovery, 2024, 10(1): 153. DOI: 10.1038/s41420-024-01916-5.
[7]	RACE N S, ANDREWS K D, LUNGWITZ E A, et al. Psychosocial impairment following mild blast-induced traumatic brain injury in rats [J]. Behavioural Brain Research, 2021, 412: 113405. DOI: 10.1016/j.bbr.2021.113405.
[8]	KIM S Y, YEH P H, OLLINGER J M, et al. Military-related mild traumatic brain injury: clinical characteristics, advanced neuroimaging, and molecular mechanisms [J]. Translational Psychiatry, 2023, 13(1): 289. DOI: 10.1038/s41398-023-02569-1.
[9]	LAI C, KOSTAS-POLSTON E A, ENGLER M B, et al. Prevalence of PTSD in active duty members with mild traumatic brain injury: systematic review and meta-analysis [J]. Military Medicine, 2024, 189(7/8): e1454–e1461. DOI: 10.1093/milmed/usae272.
[10]	CHEN T, ZHU J, WANG Y H, et al. Arc silence aggravates traumatic neuronal injury via mGluR1-mediated ER stress and necroptosis [J]. Cell Death & Disease, 2020, 11(1): 4. DOI: 10.1038/s41419-019-2198-5.
[11]	HENTER I D, PARK L T, ZARATE C A JR. Novel glutamatergic modulators for the treatment of mood disorders: current status [J]. CNS Drugs, 2021, 35(5): 527–543. DOI: 10.1007/s40263-021-00816-x.
[12]	BARACALDO-SANTAMARÍA D, ARIZA-SALAMANCA D F, CORRALES-HERNÁNDEZ M G, et al. Revisiting excitotoxicity in traumatic brain injury: from bench to bedside [J]. Pharmaceutics, 2022, 14(1): 152. DOI: 10.3390/pharmaceutics14010152.
[13]	LEE H W, CHOI J, SHIN H, et al. Preso, a novel PSD-95-interacting FERM and PDZ domain protein that regulates dendritic spine morphogenesis [J]. Journal of Neuroscience, 2008, 28(53): 14546–14556. DOI: 10.1523/JNEUROSCI.3112-08.2008.