A neuropeptide precursor in cerebellum: proenkephalin exists in subpopulations of both neurons and astrocytes.

Spruce, Barbara A.; Curtis, Rory; Wilkin, Graham P.; Glover, David M.

doi:10.1002/j.1460-2075.1990.tb08303.x

Cited by 108 publications

(66 citation statements)

References 26 publications

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“…Lastly, morphine might perturb proenkephalin gene expression. Proenkephalin is expressed by astrocytes in vivo 42 and in vitro 13,25,36,42,45,51 . Altered proenkephalin expression may, in turn, modulate opioiddependent astrocyte growth by an autocrine and/or paracrine mechanism(s) 13 .…”

Section: Discussionmentioning

confidence: 99%

Morphine alters astrocyte growth in primary cultures of mouse glial cells: evidence for a direct effect of opiates on neural maturation

Stiene‐Martin

Gurwell

Hauser

1991

Developmental Brain Research

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SUMMARYTo determine whether exogenous opiate drugs with abuse liability directly modify neural growth, the present study investigated the effects of morphine on astrocyte proliferation and differentiation in primary cultures of murine glial cells. The results indicate that morphine decreases glial cell production in a dose-dependent, naloxone reversible manner. Most notably, gliogenesis virtually ceased in the presence of 10 −6 M morphine during the first week in culture, whereas 10 −8 M or 10 −10 M morphine caused an intermediate suppression of growth compared to control or 10 −6 M morphine treated cultures. Moreover, morphine-treatment inhibited [ 3 H]thymidine incorporation by glial fibrillary acidic protein (GFAP) immunoreactive, flat (type 1) astrocytes, suggesting that the decrease in glial cell production was due in part to an inhibition of astrocyte proliferation. Morphine also caused significant increases in both cytoplasmic area and process elaboration in flat (type 1) astrocytes indicating greater morphologic differentiation. In the above experiments, morphine-dependent alterations in astrocyte growth were antagonized by naloxone, indicating that morphine action was mediated by specific opioid receptors. These observations suggest that opiate drugs can directly modify neural growth by influencing two critical developmental events in astrocytes, i.e., inhibiting proliferation and inducing morphologic differentiation.

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Section: Discussionmentioning

confidence: 99%

Morphine alters astrocyte growth in primary cultures of mouse glial cells: evidence for a direct effect of opiates on neural maturation

Stiene‐Martin

Gurwell

Hauser

1991

Developmental Brain Research

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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

122

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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“…Subpopulations of developing cerebellar neural cells express the opioid mRNA and/or peptide products (22,46,61,79) and opioid receptors (34,41,65,73). Cerebellar morphogenesis can be modified by manipulating endogenous opioid systems (21,23,73,77) or opiate drugs (74)(75)(76).…”

Section: Introductionmentioning

confidence: 99%

“…Not only is the rate of their dendritic growth affected by endogenous opioids in vivo (21), but subpopulations of developing Purkinje cells themselves express proenkephalin mRNA (46,61) and/or contain enkephalin immunoreactivity (79). Purkinje cells are important in cerebellar organization both during development (60) and in the adult (47).…”

Section: Introductionmentioning

confidence: 99%

Morphine Inhibits Purkinje Cell Survival and Dendritic Differentiation in Organotypic Cultures of the Mouse Cerebellum

Hauser

Gurwell

Turbek

1994

Experimental Neurology

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The effects of morphine on the morphogenesis and survival of calbindin-D 28k immunoreactive Purkinje cells was studied in organotypic explant cultures isolated from 1-or 7-day-old mouse cerebella. To reduce experimental variability, bilaterally matched pairs of organotypic cultures were used to compare the effects of opiate drug treatment. One explant within each pair was untreated, while the remaining explant was continuously treated for 7 to 10 days with morphine, morphine plus naloxone, or naloxone alone. In explants derived from 1-day-old mice, morphine treatment significantly reduced Purkinje cell dendritic length compared to symmetrically-matched untreated control explants. The concentration of morphine estimated to cause a half-maximal reduction (EC 50 ) in dendritic length was 4.9 × 10 −8 M. At higher concentrations (EC 50 = 3.6 × 10 −6 M), morphine also significantly decreased the number of Purkinje cells in explants from 1-day-old mice compared to untreated explants. Electron microscopy identified increased numbers of degenerating Purkinje cells in explants derived from 1-day-old mice. This showed that high concentrations (10 −5 M) of morphine reduced Purkinje cell numbers by decreasing their rate of survival. In explants derived from 7-day-old mice, morphine (10 −5 M) neither affected Purkinje cell dendritic length nor cell numbers compared to symmetrically-matched untreated (control) explants. Collectively, these findings suggest that morphine per se, through a direct action on the cerebellum, can affect Purkinje cell differentiation and survival. The results additionally suggest there is a critical period during development when Purkinje cells are especially vulnerable to the effects of morphine.

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A neuropeptide precursor in cerebellum: proenkephalin exists in subpopulations of both neurons and astrocytes.

Cited by 108 publications

References 26 publications

Morphine alters astrocyte growth in primary cultures of mouse glial cells: evidence for a direct effect of opiates on neural maturation

Morphine alters astrocyte growth in primary cultures of mouse glial cells: evidence for a direct effect of opiates on neural maturation

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

Morphine Inhibits Purkinje Cell Survival and Dendritic Differentiation in Organotypic Cultures of the Mouse Cerebellum

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