Early Life Stress Decreases Cell Proliferation And The Number Of Putative Adult Neural Stem Cells In The Adult Hypothalamus

Stress is a potent environmental factor that can confer potent and enduring effects on brain structure and function. Exposure to stress during early life (ELS) has been linked to a wide range of consequences later in life. In particular, ELS exerts lasting effects on neurogenesis in the adult hippocampus, suggesting that ELS is a significant regulator of adult neural stem cell numbers and function. Here, we investigated the effect of ELS on cell proliferation and the numbers of neural stem/precursor cells in another neurogenic region: the hypothalamus of adult mice. We show that ELS has long-term suppressive effects on cell proliferation in the hypothalamic parenchyma and reduces the numbers of putative hypothalamic neural stem/precursor cells at 4 months of age. Specifically, ELS reduced the number of PCNA + cells present in hypothalamic areas surrounding the 3rd ventricle with a specific reduction in the proliferation of Sox2+/Nestin-GFP + putative stem cells present in the median eminence at the base of the 3rd ventricle. Furthermore, ELS reduced the total numbers of beta-tanycytes lining the ventral 3rd ventricle, without affecting alpha-tanycyte numbers in more dorsal areas. These results are the first to indicate that ELS significantly reduces proliferation and beta-tanycyte numbers in the adult hypothalamus, and may have (patho)physiological consequences for metabolic regulation or other hypothalamic functions in which beta-tanycytes are involved.LAY SUMMARYWe show for the first time, long-lasting effects of exposure to early life stress on cellular plasticity in the hypothalamus of adult mice.Stress in the first week of life resulted in reduced numbers of (proliferating) stem cells in specific subregions of the hypothalamus at an adult age.This loss of stem cells and decreased proliferation highlights how early life stress can affect hypothalamic functions in later life.