Dual influences of early life stress induced by limited bedding on walking adaptability and Bdnf/TrkB and Drd1/Drd2 gene expression in different mouse brain regions

• Published in: Behavioural brain research Vol. 359; pp. 66 - 72
• Main Authors: Wearick-Silva, L.E., Orso, R., Martins, L.A., Creutzberg, K.C., Centeno-Silva, A., Xavier, L.L., Grassi-Oliveira, R., Mestriner, R.G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2019
• Subjects: Adaptation, Physiological - physiology; Adaptation, Psychological - physiology; Animals; Anxiety - physiopathology; BDNF; Brain - growth & development; Brain - metabolism; Brain-Derived Neurotrophic Factor - metabolism; Dopamine; Early life stress; Gene Expression Regulation; Male; Membrane Glycoproteins - metabolism; Mice, Inbred C57BL; Models, Animal; Phenotype; Protein-Tyrosine Kinases - metabolism; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D2 - metabolism; Stress, Psychological - physiopathology; Walking - physiology; Walking adaptability; Walking adaptability; Early life stress; Dopamine; BDNF
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2018.10.025

•Exposure to early life stress leads to distinct walking adaptability phenotypes within the Limited Bedding (LB) group.•BDNF expression in the mPFC was increased in both the LB-IP and LB-SP subgroups.•A strong negative correlation was found between walking adaptability performance and BDNF exon IV in the motor cortex.•Drd1 and Drd2 expression in the hippocampus were negatively correlated with the performance in the Ladder Walking Task.•Drd1 was differentially expressed in the mPFC and Cerebellum according to the performance in the Ladder Walking Task. Introduction Evidence suggests early life stress impairs development, quality of life and increases vulnerability to disease. One important aspect of the stress experience is its impact on cognitive-motor performance, which includes the ability to adapt walking according to the environmental conditions. This study aimed to investigate how early-life stress affects walking adaptability of mice, while investigating BDNF/TrkB and Drd1/Drd2 expression in different brain regions. Methods Briefly, we exposed male C56BL/6 to the limited bedding protocol (LB) from post-natal day (PND) 2 to PND9 and then tested animals in the ladder walking task at PND60. RT-qPCR was used to investigate gene expression in the mPFC, hippocampus, motor cortex and cerebellum 2 h after the task Results LB induced a wide range of variability and therefore two distinct subgroups of animals within the LB group were established: a) superior performance (LB-SP); and b) inferior performance (LB-IP), compared to controls. Additionally, Drd1 gene expression was increased in the mPFC of LB-IP animals and in the cerebellum of LB-SP animals, while Drd2 expression was reduced in the hippocampus of the LB-IP group. BDNF exon IV gene expression in the mPFC and motor cortex was increased in both the LB-IP and LB-SP subgroups. TrkB gene expression in the hippocampus was reduced in the LB-IP group. A strong negative correlation was found between walking adaptability performance and BDNF exon IV gene expression in the motor cortex. Conversely, a positive correlation was found between walking adaptability performance and TrkB expression in the mPFC and a negative correlation in the hippocampus. Both Drd1 and Drd2 gene expression were negatively correlated with the ability to adapt walking. Conclusions Overall, our findings suggest exposure to early life stress leads to distinct walking adaptability phenotypes, which may be related to Drd1, Drd2, Bdnf exon IV and TrkB gene expression in brain regions that influence walking adaptability.