Subtle movement shifts may enable earlier Parkinson's detection

Midbrain dopamine (DA) neurons, located in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), are essential for regulating movement, emotion, and reward processing. Dysfunction of DA neurons in the SNc has been linked to the Parkinson's disease (PD). Previous research mostly focuses on the functions of DA neurons in mood regulation and reward mechanisms. Their role in more subtle and spontaneous behaviors remains poorly understood.

In a study published in Translational Psychiatry, a team led by Prof. LIU Xuemei and Prof. WEI Pengfei from the Shenzhen Institutes of Advanced Technology of the Chinese Academy of Sciences discovered that behaviors such as rearing, walking, and hunching are associated with the loss of SNc DA neurons, but not VTA DA neurons. These subtle features serve as key behavioral biomarkers of SNc DA neuron loss, enhancing the translational value of PD models.

Using a machine learning-enhanced three-dimensional spontaneous behavior analysis system, researchers examined the detailed motor behaviors in two mouse models of dopamine neuron depletion: a subacute MPTP-induced PD model and an AAV-mediated DA neuron loss model. This approach enabled the capture of detailed and nuanced behavioral features that traditional two-dimensional methods may overlook.

Researchers observed reductions in rearing and hunching behavior in the PD model, which correlates directly with the loss of DA neurons in the SNc but not the VTA. Although overall motor deficits were not significant, notable behavioral lateralization was revealed in the PD mice.

Moreover, using the AAV-induced ablation model, researchers confirmed that climbing, a behavior similar to rearing, was also strongly correlated with the loss of DA neurons in the SNc, and the damage to SNc neurons significantly reduced motor function and influenced the lateralization of movement.

These findings highlight the significance of rearing behavior and behavioral lateralization as potential behavioral markers for tracking the progression of PD. "Connecting behavioral changes with targeted neural damage advances the understanding of PD progression and offers valuable insights into improving treatment strategies," said Prof. LIU.