Developmental expression of the proenkephalin and prosomatostatin genes in cultured cortical and cerebellar astrocytes

Shinoda, Hisaharu; Marini, Ann M.; Schwartz, Joan P.

doi:10.1016/0165-3806(92)90220-q

Cited by 35 publications

(17 citation statements)

References 32 publications

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“…2 C and D), histological analyses of the NL after electrical damage were not reported (5 The activation of AVP mRNA and AVP synthesis in pituicytes may be due to osmosensitivity of these cells (30), or the stimulus may come from blood-borne factors secreted by other nerve cells in response to salt loading. Proenkephalin, prosomatostatin, and proangiotensinogen mRNAs and enkephalin peptides have recently been shown to be present in brain astrocytes, in vivo and in culture, upon various stimulations (31)(32)(33)(34). Such findings, together with the present study demonstrating the activation of pituicytes to synthesize AVP mRNA and AVP upon osmotic stimulation, suggest that glial cell-derived neuropeptides or their mRNAs may play an important physiological role in cellular communication within the nervous system.…”

Section: Discussionsupporting

confidence: 61%

Localization of vasopressin mRNA and immunoreactivity in pituicytes of pituitary stalk-transected rats after osmotic stimulation.

Leeuwen²,

Tracer³

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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The presence of [arginine] vasopressin (AVP) mRNA and AVP immunoreactivity in pituicytes of the neural lobe (NL) of intact and pituitary stalk-transected rats, with and without osmotic stimulation, was examined. AVP mRNA was analyzed by Northern blotting, as well as by in situ hybridization in combination with immunocytochemistry using anti-glial fibrillary acidic protein (GFAP) as a marker for pituicytes. In intact rats, a poly(A) tail-truncated 0.62-kb AVP mRNA was detected in the NL and was found to increase 10-fold with 7 days of continuous salt loading. Morphological analysis of the NL of 7-day salt-loaded rats revealed the presence of AVP mRNA in a significant number of GFAPpositive pituicytes in the NL and in areas most probably containing nerve fibers. Eight days after pituitary stalk transection the NL AVP mRNA diminished in animals given water to drink, whereas in those given 2% saline for 18 h followed by 6 h of water, a treatment repeated on 6 successive days beginning 2 days after surgery, the 0.62-kb AVP mRNA was present. The AVP mRNA in the pituitary stalk-transected, salt-loaded rats showed an exclusive cellular distribution in the NL, indicative of localization in pituicytes. Immunoelectron microscopy showed the presence of AVP immunoreactivity in a subpopulation of pituicytes 7 and 10 days after pituitary stalk transection in salt-loaded animals, when almost all AVP fibers had disappeared from the NL. These data show that a subset of pituicytes in the NL is activated to synthesize AVP mRNA and AVP in response to osmotic stimulation.The [arginine] vasopressin (AVP) gene is abundantly expressed in magnocellular neurons of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) in the hypothalamus (1). However, recent studies have shown the presence of AVP mRNA in the neural lobe (NL) of the pituitary as well, where the axons of these neurons terminate. This NL mRNA is shorter than that present in the hypothalamus due to a truncated poly(A) tail and is up-regulated during osmotic stimulation (2-5). After disconnection of the hypothalamoneurohypophysial tract by electrically damaging the ventromedial hypothalamic area, the AVP mRNA disappeared from the NL (5). This latter observation, together with the detection of AVP mRNA at the electron microscopic level in a subset of axonal swellings in the median eminence and NL (6), has led investigators to propose that the NL AVP mRNA is derived from the hypothalamic magnocellular neurons and is axonally transported to the NL (5, 6). Furthermore, the poly(A) tail of this AVP mRNA appears to be truncated during axonal transport (7). The existing data, however, do not fully exclude the possibility that some of the NL AVP mRNA is expressed in pituicytes.In this study, we have carried out in situ hybridization histochemistry in combination with immunocytochemistry, using a glial fibrillary acidic protein (GFAP) antibody as a marker for the pituicytes (8, 9) to examine the expression of AVP mRNA in these astrocytes in the NL. Studies were conducte...

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Section: Discussionsupporting

confidence: 61%

Localization of vasopressin mRNA and immunoreactivity in pituicytes of pituitary stalk-transected rats after osmotic stimulation.

Leeuwen²,

Tracer³

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition, age-related factors also affect opioid expression by individual astrocytes (Gurwell et al, 1996;Shinoda et al, 1992). There is an increase and subsequent fall in the proportion of astrocytes expressing receptors with maturation in vitro (Gurwell et al, 1996).…”

Section: Introductionmentioning

confidence: 98%

Regional, developmental, and cell cycle-dependent differences in ?, ?, and ?-opioid receptor expression among cultured mouse astrocytes

Stiene‐Martin

Zhou

Hauser

1998

Glia

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The diversity of opioid receptor expression was examined in astrocytes in low-density and nondividing (confluent) cultures from the cerebral cortex, hippocampus, cerebellum, and striatum of 1-day-old mice. μ, δ, and κ Opioid receptor expression was assessed in individual cells immunocytochemically, by using flow cytometry, and functionally by examining agonist-induced changes in intracellular calcium ([Ca 2+ ] i ). Significant spatial and temporal differences were evident in the pattern of expression of μ, δ, and κ receptors among astrocytes. In low-density cultures, greater proportions of astrocytes expressed μ-opioid receptor immunoreactivity in the cerebral cortex and hippocampus (26-34%) than in the cerebellum or striatum (7-12%). At confluence, a greater percentage of astrocytes in cerebellar (26%) and striatal (30%) cultures expressed μ-immunoreactivity. Fewer astrocytes possessed δ-immunoreactivity in low-density striatal cultures (8%) compared to other regions (16-22%). The proportion of δ receptorexpressing astrocytes declined in the cerebellum but increased in the hippocampus. κ-Opioid receptors were uniformly expressed by 27-34% of astrocytes from all regions, except in cortical cultures where the proportion of κ expressing cells was 38% at low-density and decreased to 22% at confluence. Selective μ (PLO 17; H-Tyr-Pro-Phe (N-Me) -D-Pro-NH 2 , δ ([D-Pen 2 , D-Pen 5 ] enkephalin) or κ (U50,488H; trans-(±) cyclohexyl] benzeneacetamide methanesulfonate) opioid receptor agonists increased [Ca 2+ ] i in subpopulations of astrocytes indicating the presence of functional receptors. Lastly, opioid receptor immunofluorescence varied during the cell division cycle. A greater proportion of astrocytes in the G 2 /M phase of the cell cycle were μ or δ receptor immunofluorescence than at G 0 /G 1 . When astrocytes were reversibly arrested in G 1 , significantly fewer cells expressed δ receptor immunofluorescence; however, upon reentry into the cell cycle immunofluorescent cells reappeared. In conclusion, opioid phenotype varies considerably among individual cultured astrocytes, and this diversity was determined by regional and developmental (age and cell cycle

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“…Not only do astrocytes themselves express endogenous opioid peptides during development 22,36,49,50,53 , but opioids inhibit astrocyte proliferation and promote premature morphologic differentiation in vitro 22,55,57 and in vivo 45,64 . Opioid drugs with abuse liability, such as heroin or morphine, affect glial development by disrupting the normal interactions between endogenous opioids and opioid receptors.…”

Section: Introductionmentioning

confidence: 99%

μ-Opioid receptor-induced Ca2+ mobilization and astroglial development: morphine inhibits DNA synthesis and stimulates cellular hypertrophy through a Ca2+-dependent mechanism

Hauser¹,

Stiene‐Martin²,

Mattson³

et al. 1996

Brain Research

124

110

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Morphine, a preferential μ opioid receptor agonist, alters astroglial development by inhibiting cell proliferation and by promoting cellular differentiation. Although morphine affects cellular differentiation through a Ca 2+ -dependent mechanism, few studies have examined whether Ca 2+ mediates the effect of opioids on cell proliferation, or whether a particular Ca 2+ signal transduction pathway mediates opioid actions. Moreover, it is uncertain whether one or more opioid receptor types mediates the developmental effects of opioids. To address these questions, the present study examined the role of μ opioid receptors and Ca 2+ mobilization in morphineinduced astrocyte development. Morphine (1 μM) and non-morphine exposed cultures enriched in murine astrocytes were incubated in Ca 2+ -free media supplemented with < 0.005, 0.3, 1.0, or 3.0 mM Ca 2+ ([Ca 2+ ] o ), or in unmodified media containing Ca 2+ ionophore (A23187), nifedipine (1 μM), dantrolene (10 μM), thapsigargin (100 nM), or L-glutamate (100 μM) for 0-72 h. μ-Opioid receptor expression was examined immunocytochemically using specific (MOR1) antibodies. Intracellular Ca 2+ ([Ca 2+ ] i ) was measured by microfluorometric analysis using fura-2. Astrocyte morphology and bromodeoxyuridine (BrdU) incorporation (DNA synthesis) were assessed in glial fibrillary acidic protein (GFAP) immunoreactive astrocytes. The results showed that morphine inhibited astroglial growth by activating μ opioid receptors. Astrocytes expressed MOR1 immunoreactivity and morphine's actions were mimicked by the selective μ agonist PL017. In addition, morphine inhibited DNA synthesis by mobilizing [Ca 2+ Collectively, the findings suggest that opioids suppress astroglial DNA synthesis and promote cellular hypertrophy by inhibiting Ca 2+ -dependent Ca 2+ release from dantrolene-sensitive intracellular stores. This implies a fundamental mechanism by which opioids affect central nervous system maturation.

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Developmental expression of the proenkephalin and prosomatostatin genes in cultured cortical and cerebellar astrocytes

Cited by 35 publications

References 32 publications

Localization of vasopressin mRNA and immunoreactivity in pituicytes of pituitary stalk-transected rats after osmotic stimulation.

Localization of vasopressin mRNA and immunoreactivity in pituicytes of pituitary stalk-transected rats after osmotic stimulation.

Regional, developmental, and cell cycle-dependent differences in ?, ?, and ?-opioid receptor expression among cultured mouse astrocytes

μ-Opioid receptor-induced Ca2+ mobilization and astroglial development: morphine inhibits DNA synthesis and stimulates cellular hypertrophy through a Ca2+-dependent mechanism

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