| 1. |
- Ploj, Karolina, et al.
(författare)
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Long-term effects of short and long periods of maternal separation on brain opioid peptide levels in male Wistar rats
- 2003
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Ingår i: Neuropeptides. - 0143-4179 .- 1532-2785. ; 37:3, s. 149-156
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Tidskriftsartikel (refereegranskat)abstract
- Environmental manipulations early in life may induce persistent alterations in adult behaviour and physiology. The underlying neural mechanisms of these responses are not yet clear. We have previously reported long-term changes in brain opioid peptide levels in male and female Sprague-Dawley rats after short periods (15 min, known as neonatal handling) of maternal separation (MS) until weaning. To study this further, we investigated behavioural and neurochemical effects of repeated MS in male Wistar rats. The rat pups were separated from their dams in litters for either 360 min (MS360) or 15 min (MS15) daily from postnatal day 1 to 21 or exposed to normal animal facility rearing. Behavioural analysis showed that MS360 rats had increased ultrasonic calls on postnatal day 5 compared to MS15 rats, but not on postnatal day 6. Moreover, the MS360 rats had more animals with higher frequency of calls at day 5 than 6 than the MS15 rats. Analysis of the opioid peptides dynorphin B and Met-enkephalin-Arg(6)Phe(7) with radioimmunoassay 7 weeks after the MS procedure, revealed long-term neurochemical changes in several brain areas and in the pituitary gland. Immunoreactive dynorphin B and Met-enkephalin-Arg(6)Phe(7) levels were affected in the hypothalamus and dynorphin B levels in the neurointermediate pituitary lobe, amygdala, substantia nigra and the periaqueductal gray. Together, these findings show that repeated periods of MS early in life in male Wistar rats affect the development of the ultrasonic call response and induce long-lasting and possibly permanent alterations in the opioid peptide systems.
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| 2. |
- Edoff, Karin, 1973-, et al.
(författare)
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Neuropeptide effects on rat chondrocytes and perichondrial cells in vitro
- 2003
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Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 37:5, s. 316-318
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Tidskriftsartikel (refereegranskat)abstract
- This study examines if cultured chondrocytes and perichondrial cells change the level of cAMP and/or cGMP in response to application of the neuropeptide calcitonin gene-related peptide (CGRP). Cells collected from the knee region of 4–8 days old rat pups were cultured in vitro. Cultures were exposed to 10−10–10−6 M CGRP during 10 minutes. The levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in the cultures and in controls were determined by radioimmunoassay. The results show that application of CGRP causes a distinctly increased level of cAMP, that was absent when CGRP was applied together with the CGRP1 receptor antagonist. The level of cGMP was not obviously altered. Hence, it is possible that terminals of primary sensory neurones present in developing cartilage influence chondrocytes and perichondrial cells via local release of CGRP.
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| 3. |
- Kilk, Kalle, et al.
(författare)
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Targeting of antisense PNA oligomers to human galanin receptor type 1 mRNA
- 2004
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Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 38:5, s. 316-324
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we have targeted positions 18–38 of the human galanin receptor type 1 (GalR1) mRNA coding sequence with different peptide nucleic acid (PNA) oligomers. This region has previously been shown to be a good antisense region and therefore we aimed to identify the subregions and/or thermodynamic parameters determining the antisense efficacy. Nine different PNA oligomers were conjugated to a cell-penetrating peptide, transportan, to enhance their cellular uptake. Concentration-dependent down-regulation of GalR1 protein expression in human melanoma cell line Bowes was measured by radioligand binding assay. No reduction of GalR1 mRNA level was observed upon PNA treatment, thus, the effect was concluded to be translational arrest. Judging from the EC50 values, antisense PNA oligomers targeting regions 24–38 (EC50 = 70 nM) or 27–38 (EC50 = 80 nM) were the most potent suppressors of protein expression. No parameter predicted by M-fold algorithm was found to correlate with the measured antisense activities. Presence of some subregions was found not to increase antisense efficiency of PNA. Presence of a short unpaired triplet between nucleotides 33 and 35 in the target region was, on the other hand, found to be the most critical for efficient GalR1 down-regulation. Thus, the results are of high impact in designing antisense oligomers. Specific results of this study demonstrate 20-fold more efficient antisense down-regulation of GalR1 as achieved before.
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| 4. |
- Woldbye, DPD, et al.
(författare)
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Neuropeptide Y and seizures: effects of exogenously applied ligands
- 2004
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Ingår i: Neuropeptides. - : Elsevier BV. - 1532-2785 .- 0143-4179. ; 38:4, s. 253-260
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Forskningsöversikt (refereegranskat)abstract
- The endogenous NPY system in the brain is centrally involved in seizure regulation. The present paper reviews the evidence that exogenously applied NPY receptor ligands can inhibit epileptic seizures in various rodent in vitro and in vivo models. Agonists at Y2 and/or Y5 receptors and antagonists at Y1 receptors appear to inhibit seizures, depending on the seizure model studied. Although progress has been made, further studies are needed using transgenic animals as well as novel selective agonists and antagonists to firmly identify the NPY receptors mediating antiepileptic effects. This may lead to the development of future antiepileptic drug treatments targeting the NPY system, (C) 2004 Elsevier Ltd. All rights reserved.
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