Upregulation in the Expression of Tryptophan Hydroxylase 2 (TPH2) in the Lower Brainstem in Depression

Abstract

In addition to affective disturbances depression is characterized by physical symptoms, which suggest dysfunction of motor, autonomic, and pain regulatory systems. These functions are modulated by serotonin (5‐HT), and extensive evidence implicates dysfunction in its neurotransmission in the pathophysiology of depression. In the current study we examined gene expression of TPH2, a key enzyme in 5‐HT synthesis, within brainstem regions that contain spinally‐projecting 5‐HTergic neurons. We collected post‐mortem human brainstem samples from depressed and control subjects, and used a combined neurochemical and histological staining approach to identify 5‐HT cell groups in the lower brainstem that are homologous with those in other species. Using radioactive in situ hybridization we detected an upregulation in TPH2 expression within: raphe obscurus, gigantocellular nucleus pars α, and raphe magnus. These regions are well‐known to regulate somatomotor, sympathetic, and nociceptive functions, and a similar increase in TPH2 expression has been reported within ascending 5‐HTergic cell groups. Taken together, these findings suggest shared molecular alterations within distinct 5‐HT circuits that mediate affective and physical manifestations of depression.Support: Pritzker Neuropsychiatric Disorders Research Consortium, 5K99MH081927‐02 (to IAK), and NARSAD Young Investigator Award (to IAK).