Magic™ Anti-DCX polyclonal antibody

Neurogenesis in the substantia nigra (SN) has been a controversial issue. Here we report that neurogenesis can be induced in the adult rodent SN by transplantation of embryoid body cells (EBCs) derived from mouse embryonic stem cells. The detection of Sox2(+) dividing (BrdU(+)) putative host neural precursor cells (NPCs) between 1 and 6 days post-transplantation (dpt) supported the neurogenic capacity of the adult SN. In agreement with the awakening of NPCs by EBCs, only host cells from implant-bearing SN were able to generate neurosphere-like aggregates in the presence of Egf and Fgf2. Later, at 15 dpt, a significant number of SN Dcx(+) neuroblasts were detected. However, a continuous BrdU administration after transplantation showed that only a fraction (about 20-30%) of those host Dcx(+) progeny derived from dividing cells and few BrdU(+) cells, some of them NeuN(+), survived up to 30 dpt. Unexpectedly, 25-30% of Dcx(+) or Psa-Ncam(+) cells at 15 dpt displayed astrocytic markers such as Gfap and S100b. Using a genetic lineage tracing strategy, we demonstrated that a large proportion of host Dcx(+) and/or Tubb3(+) neuroblasts originated from Gfap(+) cells. Remarkably, new blood vessels formed in association with the neurogenic process that, when precluded, caused a reduction in neuroblast production. Accordingly, two proteins secreted by EBCs, Fgf2 and Vegf, were able to promote the emergence of Dcx(+)/Psa-Ncam(+), Tubb3(+) and NeuN(+)/BrdU(+) cells in vivo in the absence of EBCs. We propose that the adult SN is a mostly silent neurogenic niche with the ability to generate new neurons by typical and atypical mechanisms. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

Background: Postpartum depression affects approximately 15% of mothers and represents a form of early life adversity for developing offspring. Postpartum depression can be treated with prescription antidepressants like fluoxetine (FLX). However, FLX can remain active in breast milk, raising concerns about the consequences of neonatal FLX exposure. The hippocampus is highly sensitive to developmental stress, and males and females respond differently to stress at many endpoints, including hippocampal plasticity. However, it is unclear how developmental exposure to FLX alters the trajectory of hippocampal development. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum depression) and concurrent FLX on hippocampal neurogenesis in male and female offspring. Methods: Female Sprague-Dawley rat dams were treated daily with either CORT or oil and FLX or saline from postpartum days 2-23. Offspring were perfused on postnatal day 31 (pre-adolescent), postnatal day 42 (adolescent), and postnatal day 69 (adult). Tissue was processed for doublecortin (DCX), an endogenous marker of immature neurons, in the dorsal and ventral hippocampus. Results: Maternal postpartum CORT reduced density of DCX-expressing cells in the dorsal hippocampus of pre-adolescent males and increased it in adolescent males, suggesting that postpartum CORT exposure disrupted the typical progression of the density of DCX-expressing cells. Further, among offspring of oil-treated dams, pre-adolescent males had greater density of DCX-expressing cells than pre-adolescent females, and maternal postpartum CORT prevented this sex difference. In pre-adolescent females, maternal postpartum FLX decreased the density of DCX-expressing cells in the dorsal hippocampus compared to saline. As expected, maternal CORT reduced the density of DCX-expressing cells in adult female, but not male, offspring. The combination of maternal postpartum CORT/FLX diminished density of DCX-expressing cells in dorsal hippocampus regardless of sex or age. Conclusions: These findings reveal how modeling treatment of postpartum depression with FLX alters hippocampal neurogenesis in developing offspring differently depending on sex, predominantly in the dorsal dentate gyrus and earlier in life.