Opioid system diversity in developing neurons, astroglia, and oligodendroglia in the subventricular zone and striatum: Impact on gliogenesis in vivo

Abstract

Accumulating evidence, obtained largely in vitro, indicates that opioids regulate the genesis of neurons and glia and their precursors in the nervous system. Despite this evidence, few studies have assessed opioid receptor expression in identified cells within germinal zones or examined opioid effects on gliogenesis in vivo. To address this question, the role of opioids was explored in the subventricular zone (SVZ) and/or striatum of 2-5-day-old and/or adult ICR mice. The results showed that subpopulations of neurons, astrocytes, and oligodendrocytes in the SVZ and striatum differentially express mu-, delta-, and/or kappa-receptor immunoreactivity in a cell type-specific and developmentally regulated manner. In addition, DNA synthesis was assessed by examining 5-bromo-2'-deoxyuridine (BrdU) incorporation into glial and nonglial precursors. Morphine (a preferential mu-agonist) significantly decreased the number of BrdU-labeled GFAP(+) cells compared with controls or mice co-treated with naltrexone plus morphine. Alternatively, in S100beta(+) cells, morphine did not significantly decrease BrdU incorporation; however, significant differences were noted between mice treated with morphine and those treated with morphine plus naltrexone. Most cells were GFAP(-)/S100beta(-). When BrdU incorporation was assessed within the total population (glia and nonglia), morphine had no net effect, but naltrexone alone markedly increased BrdU incorporation. This finding suggests that DNA synthesis in GFAP(-)/S100beta(-) cells is tonically suppressed by endogenous opioids. Assuming that S100beta and GFAP, respectively, distinguish among younger and older astroglia, this implies that astroglial replication becomes increasingly sensitive to morphine during maturation, and suggests that opioids differentially regulate the development of distinct subpopulations of glia and glial precursors.

Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling

“…The absence of direct transcriptional effects of morphine in astrocytes in the current study may be explained by the low level of l opioid receptors in our cultures, which is consistent with previous reports (Ruzicka et al, 1995;Stiene-Martin et al, 1998). Similarly, earlier studies have shown that a very low fraction of astrocytes in the striatum of adult mice express lopioid receptors (Stiene-Martin et al, 2001). An alternative explanation assumes qualitative differences in the intercellular signaling pathway elicited by activation of opioid receptors between different cell types (e.g., Rothe et al, 2012).…”

“…It has been shown that acute morphine stimulation can induce calcium signaling El-Hage et al, 2005) and ERK phosphorylation (Belcheva et al, 2003), while prolonged exposure affected proliferation (Stiene-Martin et al, 2001) and proteomic profile (Suder et al, 2009) in primary astrocytes. The absence of direct transcriptional effects of morphine in astrocytes in the current study may be explained by the low level of l opioid receptors in our cultures, which is consistent with previous reports (Ruzicka et al, 1995;Stiene-Martin et al, 1998).…”

Synergistic increases in intracellular Ca2+, and the release of MCP‐1, RANTES, and IL‐6 by astrocytes treated with opiates and HIV‐1 Tat

“…Neurons and astrocytes in the striatum Stiene-Martin et al, 2001;Nath et al, 2002), as well as neural progenitors in the striatum and elsewhere (Reznikov et al, 1999;Eisch et al, 2000;StieneMartin et al, 2001;Persson et al, 2003), widely express μ-opioid receptors and morphine can exacerbate the neurotoxic effects of HIV-derived proteins in neurons. Potential opiate-HIV interactions in astroglia are of interest because of the importance of astroglia in providing metabolic and trophic support for neurons and because of their emerging importance in neuroimmunology.…”

Glial-restricted precursors: Patterns of expression of opioid receptors and relationship to human immunodeficiency virus-1 Tat and morphine susceptibility in vitro

“…The particular effects seen for each receptor type are contextual and differ among cell types and at different stages of development. Immature neurons Eisch and Harburg, 2006;Narita et al, 2006a), astrocytes (Stiene-Martin and Hauser, 1990;Eriksson et al, 1990;Eriksson et al, 1991;Stiene-Martin and Hauser, 1991;Hauser et al, 1996;Stiene-Martin et al, 1998;Belcheva et al, 2005), oligodendrocytes (Knapp et al, 1998;Stiene-Martin et al, 2001), and their precursors (Persson et al, 2003a;Persson et al, 2003b;Persson et al, 2006;Kim et al, 2006) can respond uniquely to opioids. For example, MOR receptor activation can inhibit proliferation in immature astroglia, while activation of the same receptor type in immature oligodendroglia increases proliferation (Knapp et al, 1998).…”