# Behavioral and Neurobiological Correlates of Resilience in the Hindlimb Unloading Mouse Model: A Longitudinal Ethogram with Neurotrophin Profile

## TL;DR

This study explores how mice adapt to simulated microgravity and finds that certain behaviors and brain chemicals predict resilience.

## Contribution

The study introduces a detailed ethogram and links specific behaviors and neurotrophin levels to resilience in hindlimb unloading.

## Key findings

- Baseline exploratory activity predicts adaptive behavioral trajectories during hindlimb unloading.
- Suspended mice show progressive reduction in NGF and BDNF levels over time.
- Behavioral adaptation correlates with changes in neurotrophin levels during suspension.

## Abstract

Among ground-based paradigms used to reproduce altered gravity exposure, the hindlimb unloading (HU) model is widely employed to simulate microgravity conditions by removing gravitational loading from the hindlimbs. Despite its extensive use, behavioral adjustments during suspension remain poorly characterized, although they may provide valuable indicators of animal welfare and individual susceptibility. Here, we comprehensively characterized the behavioral profile of mice during and after HU using a dedicated ethogram, with the aim of identifying behavioral markers associated with individual coping strategies. Several exploratory and postural behaviors showed marked time-dependent modulation, with baseline exploratory activity predicting a more adaptive behavioral trajectory during suspension, possibly indicative of greater resilience. In parallel, brain levels of the neurotrophins NGF and BDNF were measured to explore their relationship with behavioral outcomes. Although no significant group differences were detected, suspended mice displayed a progressive reduction in both neurotrophins over time, which paralleled behavioral adaptation. Together, these findings indicate that specific exploratory behaviors represent reliable predictors of resilience to HU, while NGF and BDNF may reflect ongoing neuroplastic processes associated with prolonged suspension.