Neurodegenerative diseases involve the loss of specific neurons, which compromises various brain functions. In Parkinson’s disease, dopaminergic (DA) neurons of the substantia nigra die, causing uncontrollable moveme...
Neurodegenerative diseases involve the loss of specific neurons, which compromises various brain functions. In Parkinson’s disease, dopaminergic (DA) neurons of the substantia nigra die, causing uncontrollable movement. Strategies to restore these neurons by transplantation have met with some success, but some patients develop graft-induced dyskinesia (GID). Aldrin-Kirk et al. transplanted fetal rat DA neurons into a rat model of Parkinson’s disease, then used adenoviruses to introduce various combinations of DREADDs (designer receptors exclusively activated by designer drugs) to either increase or decrease dopamine released from the grafted tissue. Activation of Gq- or Gs-coupled DREADDs (hM3Dq or rM3Ds, both responding to CNO) enhanced dopamine release, whereas activation of a Gi-coupled DREADD [KORD, which responds to salvinorin B (SalB)] reduced dopamine release and blocked the effect of CNO. Although CNO administration improved motor behavior in the grafted rats expressing hM3Dq and rM3Ds or rM3Ds alone, these animals developed GID. GID did not occur in rats expressing hM3Dq and KORD, suggesting that Gs signaling is responsible for GID. The serotonin receptors 5-HT4, 5-HT5, and 5-HT6 are Gs-coupled receptors implicated in GID, and administration of receptor-specific agonists to the rats expressing hM3Dq and KORD showed that 5-HT6 stimulation resulted in aberrant behaviors similar to those induced by CNO. Local administration of the 5-HT6 agonist produced an electrophysiological response in the transplanted neurons similar to that produced by local CNO application in the hM3Dq and KORD-expressing animals. Staining of the transplanted tissue showed that a subset of the DA neurons was positive for 5-HT6 and that the transplant and surrounding striatum were innervated by serotonin-releasing neurons (positive for the serotonin transporter SERT). Transplants of dissociated human fetal ventral mesencephalon or human embryonic stem cells in immunosuppressed rats showed
The gold and silver plasmon nanoparticles have been synthesized on the c-sapphire and p-silica substrates by the pulsed laser deposition method. It has been demonstrated that the variation of the thickness of as-grown...
The gold and silver plasmon nanoparticles have been synthesized on the c-sapphire and p-silica substrates by the pulsed laser deposition method. It has been demonstrated that the variation of the thickness of as-grown gold and silver films permits producing the plasmon nanoparticles with different size and density. It provides the retuning of the frequency of surface plasmon resonance in wide spectral region.
Ob ein degenerativ verändertes Hüftgelenk gelenkerhaltend operiert werden kann, hängt von der Ursache und der Schwere der Veränderungen ab. Lesen Sie im nachfolgenden Beitrag, welche Möglichke...
Ob ein degenerativ verändertes Hüftgelenk gelenkerhaltend operiert werden kann, hängt von der Ursache und der Schwere der Veränderungen ab. Lesen Sie im nachfolgenden Beitrag, welche Möglichkeiten es gibt, damit Sie insbesondere jüngere Patienten richtig beraten können.
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