TIME COURSE OF MORPHINE'S EFFECTS ON ADULT HIPPOCAMPAL SUBGRANULAR ZONE REVEALS PREFERENTIAL INHIBITION OF CELLS IN S PHASE OF THE CELL CYCLE AND A SUBPOPULATION OF IMMATURE NEURONS
- Author(s)
- Arguello, AA; Harburg, GC; Schonborn, JR; Mandyam, CD; Yamaguchi, M; Eisch, AJ;
- Details
- Publication Year 2008-11-11,Volume 157,Issue #1,Page 70-79
- Journal Title
- NEUROSCIENCE
- Publication Type
- Journal Article
- Abstract
- Opiates, such as morphine, decrease neurogenesis in the adult hippocampal subgranular zone (SGZ), raising the possibility that decreased neurogenesis contributes to opiate-induced cognitive deficits. However, there is an incomplete understanding of how alterations in cell cycle progression and progenitor maturation contribute to this decrease. The present study examined how morphine regulates progenitor cell cycle, cell death and immature SGZ neurons (experiment 1) as well as the progression of SGZ progenitors through key stages of maturation (experiment 2). In experiment 1, mice received sham or morphine pellets (s.c., 0 and 48 h) and bromodeoxyuridine (BrdU) 2 h prior to sacrifice (24, 72 or 96 h). Morphine decreased both the number of S phase and total cycling cells, as there were fewer cells immunoreactive (IR) for the S phase marker BrdU and the cell cycle marker Ki67. The percentage of Ki67-IR cells that were BrdU-IR was decreased after 24 but not 96 h of morphine, suggesting a disproportionate effect on S phase cells relative to all cycling cells at this time point. Cell death (activated caspase-3 counts) was increased after 24 but not 96 h. In experiment 2, nestin-green fluorescent protein (GFP) mice given BrdU 1 day prior to morphine or sham surgery (0 and 48 h, sacrifice 96 h) had fewer Ki67-IR cells, but no change in BrdU-IR cell number, suggesting that this population of BrdU-IR cells was less sensitive to morphine. Interestingly, examination of key stages of progenitor cell maturation revealed that morphine increased the percent of BrdU-IR cells that were type 2b and decreased the percent that were immature neurons. These data suggest that chronic morphine decreases SGZ neurogenesis by inhibiting dividing cells, particularly those in S phase, and progenitor cell progression to a more mature neuronal stage. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- RAT DENTATE GYRUS; GENERATED GRANULE CELLS; CENTRAL-NERVOUS-SYSTEM; ADHESION MOLECULE; DECREASES NEUROGENESIS; SYNAPTIC PLASTICITY; PROLIFERATING CELLS; NEURAL PRECURSORS; PROGENITOR CELLS; CRITICAL PERIOD
- Publisher's Version
- https://doi.org/10.1016/j.neuroscience.2008.08.064
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2008-11-11 12:00:00