TY - JOUR

T1 - A Truncated Receptor TrkB Isoform (TrkB.T1) in Mechanisms of Genetically Determined Depressive-like Behavior of Mice

AU - Alsalloum, Marah

AU - Ilchibaeva, Tatiana

AU - Tsybko, Anton

AU - Eremin, Dmitry

AU - Naumenko, Vladimir

N1 - The animal housing was implemented using the equipment of the Center for Laboratory Animal Genetic Resources at the ICG SB RAS with support from the Ministry of Science and Higher Education of the Russian Federation (unique identifier of the project: RFMEFI62119X0023). Microscopy was performed at the Microscopy Center of the Institute of Cytology and Genetics, SB RAS, Russia. DNA sequencing was performed at the SB RAS Genomics Core Facility.

PY - 2023/9/19

Y1 - 2023/9/19

N2 - Depression is a mental disorder that significantly reduces quality of life, and the discovery of new drug targets is an urgent problem for modern neuroscience. Brain-derived neurotrophic factor (BDNF) and its receptors have been found to participate in mechanisms of depression and antidepressant drugs' action. In this study, we focused on a less-studied truncated isoform of receptor TrkB: TrkB.T1. Initially, we noticed that the level of TrkB.T1 is low in the hippocampus of Antidepressant-Sensitive Cataleptics (ASC) mice, which are characterized by genetically determined depressive-like behavior in contrast to "normal" C57BL/6J mice. Next, overexpression of TrkB.T1 receptor in hippocampal neurons of ACS mice was induced to clarify the role of this receptor in mechanisms of depressive-like behavior. TrkB.T1 overexpression lowered BDNF protein concentration in the hippocampus. On the behavioral level, TrkB.T1 overexpression severely decreased aggression and enhanced social behavior. Additionally, this excess of receptor TrkB.T1 slightly promoted anxiety and depressive-like behavioral traits without affecting learning and memory. Our results show that this TrkB isoform participates in the control of aggression, anxiety, and depressive-like behavior and in the regulation of BDNF system functioning in ASC mice (genetically predisposed to depressive-like behavior). Considering our findings, we believe that hippocampal receptor TrkB.T1 can be a drug target for the correction of behavioral pathologies.

AB - Depression is a mental disorder that significantly reduces quality of life, and the discovery of new drug targets is an urgent problem for modern neuroscience. Brain-derived neurotrophic factor (BDNF) and its receptors have been found to participate in mechanisms of depression and antidepressant drugs' action. In this study, we focused on a less-studied truncated isoform of receptor TrkB: TrkB.T1. Initially, we noticed that the level of TrkB.T1 is low in the hippocampus of Antidepressant-Sensitive Cataleptics (ASC) mice, which are characterized by genetically determined depressive-like behavior in contrast to "normal" C57BL/6J mice. Next, overexpression of TrkB.T1 receptor in hippocampal neurons of ACS mice was induced to clarify the role of this receptor in mechanisms of depressive-like behavior. TrkB.T1 overexpression lowered BDNF protein concentration in the hippocampus. On the behavioral level, TrkB.T1 overexpression severely decreased aggression and enhanced social behavior. Additionally, this excess of receptor TrkB.T1 slightly promoted anxiety and depressive-like behavioral traits without affecting learning and memory. Our results show that this TrkB isoform participates in the control of aggression, anxiety, and depressive-like behavior and in the regulation of BDNF system functioning in ASC mice (genetically predisposed to depressive-like behavior). Considering our findings, we believe that hippocampal receptor TrkB.T1 can be a drug target for the correction of behavioral pathologies.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85172478203&origin=inward&txGid=3e988ea492aa7749a1c8f5198e8fa9e3

UR - https://www.mendeley.com/catalogue/694f0045-0dad-3cbd-acc8-94ab745e1ade/

U2 - 10.3390/biomedicines11092573

DO - 10.3390/biomedicines11092573

M3 - Article

C2 - 37761014

VL - 11

JO - Biomedicines

JF - Biomedicines

SN - 2227-9059

IS - 9

M1 - 2573

ER -