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

Abstract

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 2h 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.

Vulnerable and resilient cognitive performance related to early life stress: The potential mediating role of dopaminergic receptors in the medial prefrontal cortex of adult mice

“…When DRD1 agonists was administered in animals during working memory task, for example, it was observed suppressive effects on dopaminergic neuronal firing in PFC in association with performance deficits (Vijayraghavan et al, ). Altered behavior phenotype was also found in a recent study from our lab (Wearick‐Silva et al, ) in association with upregulation of DRD1 in animals exposed to ELS through Limited Bedding protocol. It suggests that stress negative effects could be shape the brain development through dopamine system contributing for behavioral dysfunctional outcomes later in life.…”

The foot fault scoring system to assess walking adaptability in rats and mice: a reliability study

“…Rodents and humans perform some similar movements to protect an injured limb and/or prevent falls [29] According to the authors, the test is a sensitive skilled task for assessing slight impairments of walking function and is useful when assessing functional recovery following brain or spinal cord injury and the effectiveness of rehabilitative therapies [14,30]. Locomotion during the ladder rung walking test is known to depend on ascending and descending neural pathways, since accurately crossing the rungs requires finely adjusted motor control, balance, limb coordination and muscle control [7,13,14].…”

“…In both cases, the ladders were elevated horizontally 30 cm above the ground, with a neutral cage placed in the starting position and the animal's home cage placed at the opposite end of the ladder (Figure 1). The between-wall distance was adjusted leaving 1 cm wider than the size of rodent to prevent the animal turning around during the crossing [13,14,24]. In the test, the animals were placed at the beginning of the ladder, walked along it, adapting their foot placement on the rungs until reaching the home cage ( Figure 1).…”

“…In irregular patterns, rungs are randomly repositioned in each trial to prevent the rodents learning the rung sequence. Thus, irregular patterns are more useful when studying walking adaptability(Figure.1, Asymmetrical Pattern)[7,13,14]. In this study, only irregular rung patterns were analyzed.…”

Pathways of Prevention: A Scoping Review of Dietary and Exercise Interventions for Neurocognition

“…Indeed, great strides have been made at multiple levels of inference, including randomized trials of clinical populations, [37][38][39][40][41]. mechanistic studies within preclinical older adults using neuroimaging modalities, [42][43][44] and animal studies linking neurobehavioral changes to alterations in mitochondrial structure, [45][46][47] neurotrophic, [48,49] and metabolic function [50,51] to underlying changes of neuropathological pathways [52][53][54]. While exciting, the abundance of data has made a systematic synthesis of the linkages between diet, exercise, and neurocognition more difficult.…”