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Lack of brain serotonin affects feeding and differentiation of newborn cells in the adult hypothalamus

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Item Type:Article
Title:Lack of brain serotonin affects feeding and differentiation of newborn cells in the adult hypothalamus
Creators Name:van Lingen, M. and Sidorova, M. and Alenina, N. and Klempin, F.
Abstract: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.
Keywords:Hypothalamus, BrdU, 5-HT, Tph2, NG2, Western-Type Diet, Animals, Mice
Source:Frontiers in Cell and Developmental Biology
ISSN:2296-634X
Publisher:Frontiers Research Foundation (Switzerland)
Volume:7
Page Range:65
Date:April 2019
Official Publication:https://doi.org/10.3389/fcell.2019.00065
PubMed:View item in PubMed

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