Rabbit Anti-DCX monoclonal antibody, clone KK1060

Neuroinflammation plays a critical role in the pathogenesis of postoperative cognitive dysfunction (POCD) of the elderly patients. Receptor-interacting protein kinase1 (RIPK1) is a key molecular switch modulating inflammation, apoptosis and necroptosis. Here, we investigated whether inhibiting RIPK1 by necrostatin-1 (Nec-1) could limit neuroinflammation and attenuate POCD in D-Galactose (D-Gal)-induced aged mice. The mice were subjected to anesthesia and partial hepatectomy, and necrostatin-1 was administered intraperitoneally 1 h prior to anesthesia and surgery. Cognitive function and movement were tested 24 h after surgery by open field, Barnes maze and puzzle box. The hippocampal tissues were collected to detect the following: neuroinflammation (Iba-1, IL-1 alpha, IL-1 beta, TNF-alpha), Necroptosis (Propidium Iodide (PI) labeling, RIPK1, nuclear transcription factor kappa B (NF-kappa beta) and neuroplasticity (doublecortin (DCX), NR2B, GluA1, GluA2). We found that anesthesia and surgery induced a significant deficit in spatial memory acquisition and impairment of executive function and memory to simple task in D-Galactose-induced aged mice. Inhibiting RIPK1 by necrostatin-1 strikingly mitigated cognitive impairment and alleviated postoperative amplified neuroinflammation, necroptosis and GluA1 loss in hippocampus. These suggest that targeting RIPK1 by necrostatin-1 may serve as a promising therapeutics for prevention of POCD in elderly patients.

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.