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DREADD Modulation o...
DREADD Modulation of Transplanted DA Neurons Reveals a Novel Parkinsonian Dyskinesia Mechanism Mediated by the Serotonin 5-HT6 Receptor
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- Aldrin-Kirk, Patrick (författare)
- Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Molecular Neuromodulation,Lund University Research Groups
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- Heuer, Andreas (författare)
- Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Utvecklings- och regenerativ neurobiologi,Molecular Neuromodulation,Lund University Research Groups,Developmental and Regenerative Neurobiology
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- Wang, Gang (författare)
- Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Molecular Neuromodulation,Lund University Research Groups
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- Mattsson, Bengt (författare)
- Lund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Utvecklings- och regenerativ neurobiologi,Neurobiology,Lund University Research Groups,Developmental and Regenerative Neurobiology
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- Lundblad, Martin (författare)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
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- Parmar, Malin (författare)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
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- Björklund, Tomas (författare)
- Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Molecular Neuromodulation,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2016
- 2016
- Engelska 14 s.
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273. ; 90:5, s. 955-968
- Relaterad länk:
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http://dx.doi.org/10... (free)
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http://www.cell.com/...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Transplantation of DA neurons is actively pursued as a restorative therapy in Parkinson's disease (PD). Pioneering clinical trials using transplants of fetal DA neuroblasts have given promising results, although a number of patients have developed graft-induced dyskinesias (GIDs), and the mechanism underlying this troublesome side effect is still unknown. Here we have used a new model where the activity of the transplanted DA neurons can be selectively modulated using a bimodal chemogenetic (DREADD) approach, allowing either enhancement or reduction of the therapeutic effect. We show that exclusive activation of a cAMP-linked (Gs-coupled) DREADD or serotonin 5-HT6 receptor, located on the grafted DA neurons, is sufficient to induce GIDs. These findings establish a mechanistic link between the 5-HT6 receptor, intracellular cAMP, and GIDs in transplanted PD patients. This effect is thought to be mediated through counteraction of the D2 autoreceptor feedback inhibition, resulting in a dysplastic DA release from the transplant.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Neuron
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