Home About us Contact
|
Home About us Contact | ||
|
|
||
Mesencephalic Precursors (mesencephalic + precursor)
Selected AbstractsSerotonin decreases generation of dopaminergic neurons from mesencephalic precursors via serotonin type 7 and type 4 receptorsDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2007J. Parga Abstract Inductive signals mediating the differentiation of neural precursors into serotonergic (5-HT) or dopaminergic neurons have not been clarified. We have recently shown that in cell aggregates obtained from rat mesencephalic precursors, reduction of serotonin levels induces a marked increase in generation of dopaminergic neurons. In the present study we treated rat neurospheres with antagonists of the main subtypes of 5-HT receptors, 5-HT transport inhibitors, or 5-HT receptor agonists, and studied the effects on generation of dopaminergic neurons. Cultures treated with Methiothepin (5-HT1,2,5,6,7 receptor antagonist), the 5-HT4 receptor antagonist GR113808;67:00,.or the 5-HT7 receptor antagonist SB 269970 showed a significant increase in generation of dopaminergic cells. Treatment with the 5-HT1B/1D antagonist GR 127935, the 5-HT2 antagonist Ritanserin, the 5-HT transporter inhibitor Fluoxetine, the dopamine and norepinephrine transport inhibitor GBR 12935, or with both inhibitors together, or 5-HT4 or 5-HT7 receptor agonists induced significant decreases in generation of dopaminergic cells. Cultures treated with WAY100635 (5-HT1A receptor antagonist), the 5-HT3 receptor antagonist Ondasetron, or the 5-HT6 receptor antagonist SB 258585 did not show any significant changes. Therefore, 5-HT4 and 5-HT7 receptors are involved in the observed serotonin-induced decrease in generation of dopaminergic neurons from proliferating neurospheres of mesencephalic precursors. 5-HT4 and 5-HT7 receptors were found in astrocytes and serotonergic cells using double immunolabeling and laser confocal microscopy, and the glial receptors appeared to play a major role. © 2006 Wiley Periodicals, Inc. J Neurobiol 67: 10,22, 2007 [source] In vitro generation and transplantation of precursor-derived human dopamine neuronsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2001Rosario Sánchez-Pernaute Abstract The use of in vitro expanded human CNS precursors has the potential to overcome some of the ethical, logistic and technical problems of fetal tissue transplantation in Parkinson disease. Cultured rat mesencephalic precursors proliferate in response to bFGF and upon mitogen withdrawal, differentiate into functional dopamine neurons that alleviate motor symptoms in Parkinsonian rats (Studer et al. [1998] Nat. Neurosci. 1:290,295). The successful clinical application of CNS precursor technology in Parkinson disease will depend on the efficient in vitro generation of human dopaminergic neurons. We demonstrate that human dopamine neurons can be generated from both midbrain and cortical precursors. Transplantation of midbrain precursor-derived dopamine neurons into Parkinsonian rats resulted in grafts rich in tyrosine hydroxylase positive neurons 6 weeks after transplantation. No surviving tyrosine hydroxylase positive neurons could be detected when dopamine neurons derived from cortical precursors were grafted. Our data demonstrate in vitro derivation of human dopamine neurons from expanded CNS precursors and encourage further studies that systematically address in vivo function and clinical potential. J. Neurosci. Res. 65:284,288, 2001. © 2001 Wiley-Liss, Inc. [source] | ||||||||||