Early life stress decreases the proliferation and numbers of adult hypothalamic neural stem cells

Abstract

Early life stress (ELS) is a potent environmental factor that can confer enduring effects on brain structure and function. Exposure to stress during early life has been linked to a wide range of physiopathological consequences later in life. In particular, ELS has been shown to have lasting effects on neurogenesis in the adult brain, suggesting that ELS is a significant regulator of adult neural stem cell function. Here, we investigated the effect of ELS on the numbers and proliferation of neural stem cells in the hypothalamus of adult mice.We show that ELS has long term negative effects on hypothalamic neural stem cell numbers and on their proliferation. Specifically, ELS reduced the total numbers of PCNA+ cells present in hypothalamic areas surrounding the 3 rd ventricle; the numbers of PCNA+/Sox2+/Nestin-GFP+ cells present in the medial eminence at the base of the 3 rd ventricle; and the number of β-tanycytes around the ventral 3rd ventricle, without affecting the numbers of α-tanycytes in more dorsal areas. These results suggest that a reduction of proliferation and tanycyte numbers contributes to the effects of ELS on the hypothalamus and its consequent physiological alterations. 7

Frontiers of stress research: the 2nd Munich Winter Conference on Stress

“…Pascal Bielefeld from Carlos Fitzsimons' lab at the University of Amsterdam addresses the question of adult neurogenesis. Building on previous work from the interaction of early life adversity and neurogenesis in the adult hippocampus, the group now extends their observations to another brain region, the hypothalamus (Bielefeld et al, 2021). The results are the first to indicate that early life stress can reduce neurogenesis in the adult hypothalamus of mice and may thereby shape the long-term metabolic effects of early life adversity.…”