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

• Main Authors: Marike van Lingen, Maria Sidorova, Natalia Alenina, Friederike Klempin
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-04-01
• Series: Frontiers in Cell and Developmental Biology
• Subjects: hypothalamus; BrdU; 5-HT; Tph2; NG2; Western-type diet
• Online Access: https://www.frontiersin.org/article/10.3389/fcell.2019.00065/full

Serotonin (5-HT) is a crucial signal in the neurogenic niche microenvironment. Dysregulation of the 5-HT system leads to mood disorders but also to changes in appetite and metabolic rate. Tryptophan hydroxylase 2-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 niche of the adult hypothalamus has 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 cell proliferation 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 cells in the hypothalamus retain fate plasticity and respond to environmental challenges. A novel link between 5-HT signaling and cell genesis in the hypothalamus could be exploited as therapeutic target in metabolic disease.