Lack of Brain Serotonin Affects Feeding and Differentiation of Newborn Cells in the Adult Hypothalamus

Serotonin (5-HT) is a crucial signal in the neurogenic nichemicroenvironment. Dysregulation of the 5-HT system leads to mood disorders but also to changes in appetite and metabolic rate. Tryptophan hydroxylase2-deficient ( Tph2-/-) mice depleted of brain 5-HT display alterations in these parameters, e.g., increased food consumption, modest impairment of sleep and respiration accompanied by a less anxious phenotype. The newly discovered neural stem cell nicheof the adult hypothalamushas potential implications of mediating stress responses and homeostatic functions. Using Tph2-/- mice, we explore stem cell behavior and cell genesis in the adult hypothalamus. Specifically, we examine precursor cellproliferation and survival in Tph2-/- mice at baseline and following Western-type diet (WD). Our results show a decline in BrdU numbers with aging in the absence of 5-HT. Furthermore, wild type mice under dietary challenge decrease cell proliferation and survival in the hypothalamic niche. In contrast, increased high-calorie food intake by Tph2-/- mice does not come along with alterations in cell numbers. However, lack of brain 5-HT results in a shift of cell phenotypes that was abolished under WD. We conclude that precursor cellsin the hypothalamusretain fate plasticity and respond to environmental challenges. A novel link between 5-HT signaling and cell genesis in the hypothalamuscould be exploited as therapeutic target in metabolic disease.