Ontogeny of proenkephalin mRNA and enkephalin peptide expression in the cerebellar cortex of the rat: spatial and temporal patterns of expression follow maturational gradients in the external granular layer and in Purkinje cells

Osborne, John G.; Kindy, Mark S.; Spruce, Barbara A.; Hauser, Kurt F.

doi:10.1016/0165-3806(93)90117-s

Cited by 19 publications

(14 citation statements)

References 56 publications

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“…Enkephalin immunoreactivity is localized in germinal zones in the cerebellum (Zagon et al . 1985; Osborne et al . 1993), and treatment with Met‐enkephalin reportedly decreases DNA synthesis in EGL neuroblasts in vivo (Zagon & McLaughlin 1991).…”

Section: Discussionmentioning

confidence: 99%

“…Findings that EGL cells transiently and coordinately express both opioid receptors and peptides in this and other studies suggest that paracrine or autocrine interactions occur among developing granule cells (Zagon et al . 1985; Osborne et al . 1993).…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, Purkinje cells, cerebellar astrocytes, as well as enkephalin‐containing mossy fibres, also express enkephalins within the developing cerebellum (Williams & Dockray 1983; Walker & King 1989; Spruce et al . 1990; Osborne et al . 1993).…”

Section: Discussionmentioning

confidence: 99%

“…1994) and proenkephalin peptides in vivo (Zagon et al . 1985; Osborne et al . 1993), and whose development is affected by opioids in vivo (Zagon & McLaughlin 1983, 1986, 1987; Zagon et al .…”

Section: Introductionmentioning

confidence: 99%

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Opioids intrinsically inhibit the genesis of mouse cerebellar granule neuron precursors in vitro: differential impact of μ and δ receptor activation on proliferation and neurite elongation

Hauser

Houdi

Turbek

et al. 2000

Eur J of Neuroscience

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104

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Although opioids are known to affect neurogenesis in vivo, it is uncertain the extent to which opioids directly or indirectly affect the proliferation, differentiation or death of neuronal precursors. To address these questions, the intrinsic role of the opioid system in neurogenesis was systematically explored in cerebellar external granular layer (EGL) neuronal precursors isolated from postnatal mice and maintained in vitro. Isolated neuronal precursors expressed proenkephalin-derived peptides, as well as specific mu and delta, but negligible kappa, opioid receptors. The developmental effects of opioids were highly selective. Morphine-induced mu receptor activation inhibited DNA synthesis, while a preferential delta2-receptor agonist ([D-Ala2]-deltorphin II) or Met-enkephalin, but not the delta1 agonist [D-Pen2, D-Pen5]-enkephalin, inhibited differentiation within the same neuronal population. If similar patterns occur in the developing cerebellum, spatiotemporal differences in endogenous mu and delta opioid ligand-receptor interactions may coordinate distinct aspects of granule neuron maturation. The data additionally suggest that perinatal exposure to opiate drugs of abuse directly interfere with cerebellar maturation by disrupting normal opioid signalling and inhibiting the proliferation of granule neuron precursors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Opioids intrinsically inhibit the genesis of mouse cerebellar granule neuron precursors in vitro: differential impact of μ and δ receptor activation on proliferation and neurite elongation

Hauser

Houdi

Turbek

et al. 2000

Eur J of Neuroscience

Self Cite

104

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show abstract

“…For instance, the spatio-temporal expression of preproenkephalin [70] and preprogalanin [71] RNA in Purkinje cells of certain lobules during the first three postnatal weeks offers new perspectives in the understanding of differential development of the anterior and posterior cerebellar lobes.…”

Section: Cortical-layer-specific Effects Of Regulatory Factors Durmentioning

confidence: 99%

Postnatal Migration of Cerebellar Interneurons

et al. 2017

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Due to its continuing development after birth, the cerebellum represents a unique model for studying the postnatal orchestration of interneuron migration. The combination of fluorescent labeling and ex/in vivo imaging revealed a cellular highway network within cerebellar cortical layers (the external granular layer, the molecular layer, the Purkinje cell layer, and the internal granular layer). During the first two postnatal weeks, saltatory movements, transient stop phases, cell-cell interaction/contact, and degradation of the extracellular matrix mark out the route of cerebellar interneurons, notably granule cells and basket/stellate cells, to their final location. In addition, cortical-layer specific regulatory factors such as neuropeptides (pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin) or proteins (tissue-type plasminogen activator (tPA), insulin growth factor-1 (IGF-1)) have been shown to inhibit or stimulate the migratory process of interneurons. These factors show further complexity because somatostatin, PACAP, or tPA have opposite or no effect on interneuron migration depending on which layer or cell type they act upon. External factors originating from environmental conditions (light stimuli, pollutants), nutrients or drug of abuse (alcohol) also alter normal cell migration, leading to cerebellar disorders.

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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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Ontogeny of proenkephalin mRNA and enkephalin peptide expression in the cerebellar cortex of the rat: spatial and temporal patterns of expression follow maturational gradients in the external granular layer and in Purkinje cells

Cited by 19 publications

References 56 publications

Opioids intrinsically inhibit the genesis of mouse cerebellar granule neuron precursors in vitro: differential impact of μ and δ receptor activation on proliferation and neurite elongation

Opioids intrinsically inhibit the genesis of mouse cerebellar granule neuron precursors in vitro: differential impact of μ and δ receptor activation on proliferation and neurite elongation

Postnatal Migration of Cerebellar Interneurons

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

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