Effects of Social Defeat Stress on Microtubule Regulating Proteins and Tubulin Polymerization
Thi-Hung Le1,2,*, Jung-Mi Oh3,*, Fatima Zahra Rami1,2, Ling Li1,2, Sung-Kun Chun3, Young-Chul Chung1,2
1Department of Psychiatry, Jeonbuk National University Medical School, Jeonju, Korea
2Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
3Department of Physiology, Jeonbuk National University Medical School, Jeonju, Korea
Correspondence to: Young-Chul Chung
Department of Psychiatry, Jeonbuk National University Medical School, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Korea
E-mail: chungyc@jbnu.ac.kr
ORCID: https://orcid.org/0000-0001-9491-1822

Sung-Kun Chun
Department of Physiology, Jeonbuk National University Medical School, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Korea
E-mail: sungkun.chun@jbnu.ac.kr
ORCID: https://orcid.org/0000-0001-9837-2299

*These authors contributed equally to this study.
Received: March 21, 2023; Revised: May 29, 2023; Accepted: June 21, 2023; Published online: August 10, 2023.
© The Korean College of Neuropsychopharmacology. All rights reserved.

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Objective: Microtubule (MT) stability in neurons is vital for brain development; instability is associated with neuropsychiatric disorders. The present study examined the effects of social defeat stress (SDS) on MT-regulating proteins and tubulin polymerization.
Methods: After 10 days of SDS, defeated mice were separated into susceptible (Sus) and unsusceptible (Uns) groups based on their performance in a social avoidance test. Using extracted brain tissues, we measured the expression levels of α-tubulin, acetylated α-tubulin, tyrosinated α-tubulin, MT-associated protein-2 (MAP2), stathmin (STMN1), phospho stathmin serine 16 (p-STMN1 [Ser16]), phospho stathmin serine 25 (p-STMN1 [Ser25]), phospho stathmin serine 38 (p-STMN1 [Ser38]), stathmin2 (STMN2), phospho stathmin 2 serine 73 (p-STMN2 [Ser73]), 78-kDa glucose-regulated protein (GRP-78), and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) using Western blot assay. The tubulin polymerization rate was also measured.
Results: We observed increased and decreased expression of acetylated and tyrosinated α-tubulin, respectively, decreased expression of p-STMN1 (Ser16) and increased expression of p-STMN1 (Ser25), p-STMN2 (Ser73) and GRP-78 and CHOP in the prefrontal cortex and/or hippocampus of defeated mice. A reduced tubulin polymerization rate was observed in the Sus group compared to the Uns and Con groups.
Conclusion: Our findings suggest that SDS has detrimental effects on MT stability, and a lower tubulin polymerization rate could be a molecular marker for susceptibility to SDS.
Keywords: Social defeat; Microtubule; Polymerization

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