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Major depression is characterized by a marked elevation of corticotropin-releasing factor (CRF) levels in the cerebrospinal fluid (CSF). CRF is mainly produced by neurons of the locus coeruleus. CRF receptors are present in brain areas known to be involved in the pathophysiology of depression, such as the locus coeruleus, the raphe nuclei, and limbic areas, and particularly in the hippocampus. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. Recently, several studies demonstrated the presence of 5-HT neurons in brain areas known to be involved in the pathophysiology of depression. Serotonergic neurons are modulated by several neurotransmitters, including CRF. In the present study, we examined whether a change in the TPH expression in brain areas known to be involved in the pathophysiology of depression is a potential mechanism of action of CRF, which may be involved in the pathogenesis of major depression. Immunohistochemical and Western blotting analysis showed a decrease in TPH expression in the hippocampal CA3 area of postmortem brain samples from depressed patients. However, the behavioral relevance of this pathological change was not confirmed in a TPH-overexpressing transgenic mouse line. A brief treatment of cultured TPH-overexpressing neuronal cells with CRF led to a marked increase in intracellular 5-HT levels. The present data suggest that a decrease in TPH expression may be involved in the pathophysiology of depression and that CRF may regulate 5-HT levels in brain areas involved in the pathophysiology of depression through the mechanisms that have been established in the raphe.Grady Memorial Hospital
For the South Carolina hospital by the same name see Grady Memorial Hospital (South Carolina)
Grady Memorial Hospital is a general hospital in Savannah, Georgia, in the United States. It is a nonprofit organization, and affiliated with the Medical
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