Developmental programming of hypothalamic feeding circuits plays an important role in metabolic regulation, and abnormalities in this programming are associated with a predisposition to obesity and other metabolic abnormalities.
In the postnatal hypothalamus, leptin is a crucial regulator of metabolic function. In the second postnatal week, there is a peak in leptin expression and it promotes axonal outgrowth from different neuronal subtypes. As these events coincide with a massive proliferation and expansion in the number of glia, Daniele M. Rottkamp et al. were interested in the role of leptin on astrogenesis. They could show that leptin also modulates the proliferation of astrocytes in the developing hypothalamus, what might be an integral feature of its trophic functions.
The image shows an immunofluorescence of the arcuate nucleus from 3-week-old control mice. The authors compared the number of different neuronal subtypes, with proopiomelanocortin (POMC) positive cells marked with ATCH antibody (Green), agouti-related protein (AgRP) expressing cells (Red) and cell nuclei marked with DAPI (Blue). The number of AgRP or POMC neurons in control mice was comparable to those in mutant mice in which the leptin receptors were deleted. Further investigation of cells in the periventricular zone of the 3rd ventricle revealed the effects of leptin on astrogenesis during early postnatal life. Double staining of astrocytes with the glial marker GFAP and the mitotic marker BrdU, along with lineage tracing studies, revealed the enhanced proliferation of astrocytes in mice after leptin treatment, and conditional removal of leptin receptors limited the proliferation.