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  • 1
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Opioids have previously been shown to affect proliferation and differentiation in various neural cell types. In the present study, cultured rat adult hippocampal progenitors (AHPs) were shown to release β-endorphin. Membrane preparations of AHPs were found to bind [125I]β-endorphin, and immunoreactivity for mu- and delta-opioid receptors (MORs and DORs), but not for kappa-opioid receptors (KORs), was found on cells in culture. Both DNA content and [3H]thymidine incorporation were reduced after a 48-h incubation with 100 µm naloxone, 10 µm naltrindole or 10 µmβ-funaltrexamine, but not nor-binaltorphimine, suggesting proliferative actions of endogenous opioids against MORs and DORs on AHPs. Furthermore, analysis of gene and protein expression after incubation with MOR and DOR antagonists for 48 h using RT-PCR and Western blotting suggested decreased signalling through the mitogen-activated protein kinase (MAPK) pathway and lowered levels of genes and proteins that are important in cell cycling. Cultures were incubated with naloxone (10 or 100 µm) for 10 days to study the effects on differentiation. This resulted in an approximately threefold increase in neurogenesis, a threefold decrease in astrogliogenesis and a 50% decrease in oligodendrogenesis. In conclusion, this study suggests that reduced signalling through MORs and DORs decreases proliferation in rat AHPs, increases the number of in vitro-generated neurons and reduces the number of astrocytes and oligodendrocytes in culture.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Voluntary running in mice and forced treadmill running in rats have been shown to increase the amount of proliferating cells in the hippocampus. Little is known as yet about the mechanisms involved in these processes. It is well known that the endogenous opioid system is affected during running and other forms of physical exercise. In this study, we evaluated the involvement of the endogenous opioids in the regulation of hippocampal proliferation in non-running and voluntary running rats. Nine days of wheel running was compared with non-running in spontaneously hypertensive rats (SHR), a rat strain known to run voluntarily. On the last 2 days of the experimental period all rats received two daily injections of the opioid receptor antagonists naltrexone or naltrindole together with injections of bromodeoxyuridine to label dividing cells. Brain sections from the running rats showed approximately a five-fold increase in newly generated cells in the hippocampus, and this increase was partly reduced by naltrexone but not by naltrindole. By contrast, both naltrexone and naltrindole increased hippocampal proliferation in non-running rats. In non-running rats the administration of naltrexone decreased corticosterone levels and adrenal gland weights, whereas no significant effects on these parameters could be detected for naltrindole. However, adrenal gland weights were increased in naltrexone- but not in naltrindole-administered running rats. In addition, in voluntary running rats there was a three-fold increase in the hippocampal levels of Met-enkephalin-Arg-Phe compared with non-runners, indicating an increase in opioid activity in the hippocampus during running. These data suggest an involvement of endogenous opioids in the regulation of hippocampal proliferation in non-running rats, probably through hypothalamic–pituitary–adrenal axis modulation. During voluntary running in SHR naltrexone altered hippocampal proliferation via as yet unknown mechanisms.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The genesis of new cells, including neurons, in the adult human brain has not yet been demonstrated. This study was undertaken to investigate whether neurogenesis occurs in the adult human brain, in regions previously identified as neurogenic in adult rodents and monkeys. Human brain tissue was ...
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Neurochemical research 15 (1990), S. 1123-1126 
    ISSN: 1573-6903
    Keywords: Morphine ; DADLE ; dynorphine ; astrocytes ; primary culture ; cortex ; μ-receptor ; δ-receptor ; κ-receptor ; cAMP ; co-localization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of μ, δ, and κ receptor-agonists on forskolin stimulated cyclic adenosine-3′, 5′-monophosphate (cAMP) formation were examined in astroglial enriched primary cultures from the cerebral cortex of newborn rats. Intracellular cAMP accumulation was quantified by radioimmunoassay. Morphine was used as a μ-receptor agonist, D-Ala-D-Leu-Enkephalin (DADLE) as a δ-receptor agonist and dynorphine 1–13 (Dyn) as a κ-receptor agonist. Basal cAMP levels were unaffected by either the opiate agonists or the antagonists used. In the presence of the cAMP stimulator forskolin, morphine had no significant effect on the cytoplasmic cAMP levels. DADLE caused a dose related inhibition of the forskolin stimulated cAMP accumulation. The effects of this δ receptor stimulation was blocked with the selective antagonist ICI 174.864. In the presence of Dyn, the forskolin stimulated cAMP accumulation was inhibited in a dose related manner. This κ receptor stimulation was blocked with the selective antagonist MR 2266. Co-administration of DADLE and Dyn resulted in a non additive inhibition of the forskolin stimulated accumulation of cAMP. These findings indicate that astroglial enriched cultures from the cerebral cortex of rats express δ and κ-receptors co-localized ont he same population of cells, and that these receptors are inhibitory coupled to adenylate cyclase.
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  • 5
    ISSN: 1573-6903
    Keywords: Astroglia ; striatum ; brain stem ; cyclic AMP ; morphine ; DADLE ; DPDPE ; dynorphin ; U-50,488H ; forskolin ; μ ; δ ; k-opiate receptors ; β-adrenoceptors ; primary culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a previous paper, δ and κ opiate receptors were shown to be co-localized on the same cell in enriched primary cultures of astroglia from neonatal rat cerebral cortex. Activation of the receptors inhibited adenylate cyclase. In this work, the presence of opiate receptors was investigated in astroglial primary cultures from neonatal rat striatum and brain stem. Cyclic adenosine 3′, 5′-monophosphate accumulation was quantified in the presence of different opioid receptor ligands after stimulation of the cyclic adenosine 3′,5′-monophosphate system with forskolin. Morphine was used as a μ receptor agonist. [d-Ala2, D-Leu5]-enkephalin or[d-Pen2,d-Pen5]-enkephalin were used as δ receptor agonists and dynorphin 1–13 or U-50,488H were used as κ receptor agonists. Specific antagonists for the respective receptors were used. After striatum or brain stem cultures had been incubated in 10−9–10−5M of each [d-Ala2,d-Leu5]-enkephalin, [d-Pen2, D-Pen5]-enkephalin and Dynorphin 1–13 or U-50,488H, dose related inhibitions of the 10−5M rorskolin stimulated cyclic adenosine 3′,5′-monophosphate accumulation were observed. The changes were reversed to the forskolin-induced control level in the presence of the respective antagonists. 10−9–10−5M morphine did not significantly change the forskolin-induced accumulation of cyclic adenosine 3′,5′-monophosphate in the cultures studied. Furthermore, cultures from cerebral cortex, striatum or brain stem were incubated with isoproterenol alone or together with morphine or [d-Ala2,d-Leu5]-enkephalin. Isoproterenol stimulated cyclic adenosine 3′,5′-monophosphate accumulation more prominently in the cerebral cortex and striatum cultures than in the brain stem cultures. Morphine did not influence isoproterenol-induced cyclic adenosine 3′,5′-monophosphate accumulation, while [d-Ala2,d-Leu5]-enkephalin inhibited the accumulation. The results indicate that astroglial cells in primary cultures from striatum, brain stem and cerebral cortex express δ andk opioid receptors linked to the adenylate cyclase/cyclic adenosine 3′,5′-monophosphate system. No μ receptors were detected, however, in the present model. Aspects of the relation between the expression of opioid peptides and opioid receptors are discussed, while speculations are also made on the functional aspects of opioid receptors on astroglia.
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