Number of serotonergic neurons in the subthalamic nucleus and globus pallidus internus could influence the effects of deep brain stimulation in Parkinson's disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is a standard treatment for Parkinson's disease (PD), with both regions exhibiting similar treatment effectiveness. However, posttreatment neuropsychiatric side effects, such as severe depression, are common, primarily due to the loss of serotonergic cells. Identifying a region with fewer serotonergic neurons could potentially reduce these side effects. This study aimed to quantify the number of serotonergic neurons in the STN and GPi. Both regions were analyzed using hematoxylin and eosin staining and immunohistochemistry. The GPi exhibited a significantly lower number and H-score of serotonergic neurons than the STN. Within the STN, the number and H-score of serotonergic neurons were higher in the medial aspect than in the lateral aspect. Three different types of neurons, large and small, were observed. In STN, large neurons were concentrated in the center and small neurons in the periphery. This distribution was not observed in GPi. In addition, the concentration of the serotonergic neurons is less in GPi. These findings suggest that the GPi may be a safer target region, potentially reducing the incidence of post-DBS depression.