| 561. |
- Persson, Anders I., 1973, et al.
(författare)
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Comparison of immunoblotted delta opioid receptor proteins expressed in the adult rat brain and their regulation by growth hormone.
- 2005
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Ingår i: Neuroscience research. - : Elsevier BV. - 0168-0102. ; 52:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- It has previously been suggested that exogenous growth hormone (GH) affect quality of life and higher brain functions through the endogenous opioid system. Recently, we showed that GH down-regulate 72 and 48 kDa delta opioid receptor (DOR) proteins in the adult rat cerebral cortex and cerebellum. In the present study, we found that an antiserum raised against the N-terminus of the DOR also recognizes a 36 kDa protein, not recognized by a C-terminus-directed antiserum. We aimed to investigate the identity of the 72, 48 and 36 kDa proteins and to further study the effects of GH on their expression in different brain regions. The expression was studied in hypophysectomized (Hx) and untreated normal female rats. One subgroup of Hx rats received GH as a daily subcutaneous injection for 19 days. Our data show that treatment with GH in Hx rats normalized the expression of the 72 kDa protein in the cerebral cortex, whereas no significant effect were observed for the 48 or 36 kDa proteins. However, GH significantly reduced the ratio between the 72 and 36 kDa proteins in different brain regions of Hx rats. Our data suggest that GH reduces the levels of a 72 kDa DOR that likely represents a dimeric form of a 36 kDa DOR post-translationally truncated at the C-terminus, and that altered receptor dimerization may be involved in GH induced effects in the central nervous system.
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| 562. |
- Persson, Anders I., 1973, et al.
(författare)
-
Differential regulation of hippocampal progenitor proliferation by opioid receptor antagonists in running and non-running spontaneously hypertensive rats.
- 2004
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Ingår i: The European journal of neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 19:7, s. 1847-55
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 563. |
- Persson, Anders I., 1973, et al.
(författare)
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Expression of delta opioid receptor mRNA and protein in the rat cerebral cortex and cerebellum is decreased by growth hormone.
- 2003
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Ingår i: Journal of neuroscience research. - : Wiley. - 0360-4012 .- 1097-4547. ; 71:4, s. 496-503
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Tidskriftsartikel (refereegranskat)abstract
- Hormones released from the pituitary have been shown to regulate the expression of different proteins in the central nervous system. We wanted to examine whether peripheral administration of bovine growth hormone (bGH) regulates the expression of delta-opioid receptor (DOR) in the cerebral cortex and cerebellum. Expression of the DOR protein was quantified using Western blot densitometry. DOR mRNA was quantified with a solution hybridization RNase protection assay. Hypophysectomized (Hx) and untreated normal female rats were included in the study. All Hx rats were hormonally treated with cortisol (400 microg/kg/day) and L-thyroxine (10 microg/kg/day) for 19 days. Hypophysectomy resulted in a threefold increase in cerebral cortex and a twofold increase in cerebellum of the DOR protein compared with normal rats. One subgroup of Hx rats received bGH (1 mg/kg body weight) as a daily subcutaneous injection for 19 days. This treatment normalized the levels of DOR protein in the cerebral cortex and cerebellum. Immunohistochemical experiments showed that GH decreased DOR expression especially in layers II-VI in cerebral cortex and in stratum moleculare in cerebellum. Quantification of DOR mRNA by solution hybridization RNase protection assay corresponded to the DOR protein measurements. We conclude that the expression of DORs in cerebral cortex and cerebellum is regulated by GH.
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| 564. |
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| 565. |
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| 566. |
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| 567. |
- Persson, Anders I, et al.
(författare)
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Non-stem cell origin for oligodendroglioma
- 2010
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 18:6, s. 669-682
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Tidskriftsartikel (refereegranskat)abstract
- Malignant astrocytic brain tumors are among the most lethal cancers. Quiescent and therapy-resistant neural stem cell (NSC)-like cells in astrocytomas are likely to contribute to poor outcome. Malignant oligodendroglial brain tumors, in contrast, are therapy sensitive. Using magnetic resonance imaging (MRI) and detailed developmental analyses, we demonstrated that murine oligodendroglioma cells show characteristics of oligodendrocyte progenitor cells (OPCs) and are therapy sensitive, and that OPC rather than NSC markers enriched for tumor formation. MRI of human oligodendroglioma also suggested a white matter (WM) origin, with markers for OPCs rather than NSCs similarly enriching for tumor formation. Our results suggest that oligodendroglioma cells show hallmarks of OPCs, and that a progenitor rather than a NSC origin underlies improved prognosis in patients with this tumor.
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| 568. |
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| 569. |
- Persson, Anders I., 1973
(författare)
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Opioids regulate proliferation of neural progenitors. A study on the effects of opioids on adult rat hippocampal progenitors in vitro and in vivo
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The opioid receptors were among the first pharmacologically described brain receptors. These opioid receptors have thereafter been shown to mediate effects on proliferation and differentiation in both the embryonal and adult central nervous system. The aim of this thesis was to investigate if cultured hippocampal progenitors from the adult rat brain expressed opioids and opioid receptors and to investigate a possible regulation by opioids on proliferation, differentiation and gene expression in these cultures. Furthermore, we wanted to extend the results and investigate if endogenous opioids regulated hippocampal proliferation in vivo by using opioid receptor antagonists in both non-running and voluntary running rats, a situation associated with increased levels of endogenous opioids. Hippocampal progenitors were found to release b-endorphin that bound to mu- (MOR) and delta- (DOR) but not kappa- (KOR) opioid receptors in vitro. Incubation with MOR or DOR antagonists reduced proliferation whereas stimulation with b-endorphin increased proliferation in these cultures, respectively. The opioid-induced proliferation involved both intracellular calcium and phosphatidylinositol 3-kinase that stimulated phosphorylation of mitogen-activated protein kinase (MAPK). Incubation with naloxone for ten days increased neurogenesis and reduced astrogliogenesis and oligodendrogenesis whereas stimulation with b-endorphin increased oligodendrogenesis but had no effect on astrogliogenesis. Using cDNA arrays, the levels of endogenous opioids were found to regulate gene expression for several cell cycle and oligodendrocyte-specific proteins. Stimulation with b-endorphin also increased Id1, but not Id3 mRNA levels. Down-regulation of Id1 protein using antisense oligonucleotides was suggested to antagonize the opioid-induced oligodendrogenesis.Using bromodeoxyuridine (BrdU), we observed a five-fold increase in hippocampal proliferation after nine days of wheel running in spontaneously hypertensive rats, a rat strain known to run voluntary. This increased BrdU labelling was reduced by peripheral administration of a preferential MOR, but not a DOR antagonist. In non-running rats, MOR and DOR antagonists increased hippocampal proliferation. In non-running, but not in running rats, the opioid receptor antagonists reduced adrenal gland weights and plasma levels of corticosterone. This stress hormone is known to reduce hippocampal neurogenesis. Running rats had three-fold higher levels of hippocampal Met-enkephalin-Arg-Phe levels compared to non-running rats, indicating increased opioid activity in hippocampus during running. These findings demonstrate that the levels of endogenous opioids, acting on MORs and DORs, regulate proliferation of adult rat hippocampal progenitors both in vitro and in vivo. Endogenous opioids were also shown to regulate differentiation and gene expression in cultures of hippocampal progenitors. Finally, we show that exercise robustly increases proliferation of hippocampal progenitors and that such an effect is partly mediated by endogenous opioids.
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| 570. |
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