Long‐term protection of the rat nigrostriatal dopaminergic system by glial cell line‐derived neurotrophic factor against 6‐hydroxydopamine
            in vivo

The goal of this study was to investigate the ability of fetal dopaminergic neurons to improve complex sensorimotor behavior. The authors obtained ventral mesencephalic tissue from 14-day-old rat fetuses. The cells were exposed to glial cell line-derived neurotrophic factor (GDNF) prior to transplantation into rats with unilateral 6-hydroxydopamine lesions of the dopaminergic nigrostriatal pathway. Animals that received 400,000 cells exposed to GDNF demonstrated significant improvement in contralateral forelimb function and showed improvement in rotational behavior faster than animals that received cells not exposed to GDNF. Increasing the number of implanted cells to 800,000 exposed to GDNF did not result in any additional improvement in functional recovery. As neural grafting procedures in the nervous system evolve and genetically engineered cells or stem cells replace fetal tissue, crucial questions about cell number and trophic regulation will need to be addressed. This study demonstrates that grafting of 400,000 cells exposed to GDNF before transplantation has a beneficial effect in the restoration of complex sensorimotor behavior.

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Glial cell line-derived neurotrophic factor-secreting human neural progenitors show long-term survival, maturation into astrocytes, and no tumor formation following transplantation into the spinal cord of immunocompromised rats

Neuroreport ◽

10.1097/wnr.0000000000000092 ◽

2014 ◽

Vol 25 (6) ◽

pp. 367-372 ◽

Cited By ~ 24

Author(s):

Geneviève Gowing ◽

Brandon Shelley ◽

Kevin Staggenborg ◽

Amanda Hurley ◽

Pablo Avalos ◽

...

Keyword(s):

Spinal Cord ◽

Cell Line ◽

Glial Cell ◽

Neurotrophic Factor ◽

Tumor Formation ◽

Neural Progenitors ◽

Term Survival ◽

Long Term Survival

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In vivo regulation of glial cell line-derived neurotrophic factor-inducible transcription factor by kainic acid

Neuroscience ◽

10.1016/s0306-4522(99)00302-4 ◽

1999 ◽

Vol 94 (2) ◽

pp. 629-636 ◽

Cited By ~ 3

Author(s):

A.J. Eisch ◽

C.-H. Lammers ◽

S. Yajima ◽

M.M. Mouradian ◽

E.J. Nestler

Keyword(s):

Transcription Factor ◽

Cell Line ◽

Glial Cell ◽

Kainic Acid ◽

Neurotrophic Factor

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A Novel Activating Mutation in the RET Tyrosine Kinase Domain Mediates Neoplastic Transformation

Molecular Endocrinology ◽

10.1210/me.2004-0447 ◽

2006 ◽

Vol 20 (7) ◽

pp. 1633-1643 ◽

Cited By ~ 10

Author(s):

Aaron Cranston ◽

Cristiana Carniti ◽

Sam Martin ◽

Piera Mondellini ◽

Yvette Hooks ◽

...

Keyword(s):

Tyrosine Kinase ◽

Cell Line ◽

Glial Cell ◽

Neurotrophic Factor ◽

Functional Characterization ◽

Kinase Domain ◽

Tyrosine Kinase Domain ◽

Exogenous Substrate

Abstract We report the finding of a novel missense mutation at codon 833 in the tyrosine kinase of the RET proto-oncogene in a patient with a carcinoma of the thyroid. In vitro experiments demonstrate that the R833C mutation induces transformed foci only when present in the long 3′ splice isoform and, in keeping with a model in which the receptor has to dimerize to be completely activated, glial cell line-derived neurotrophic factor stimulation leads the RETR833C receptor to a higher level of activation. Tyrosine kinase assays show that the RETR833C long isoform has weak intrinsic kinase activity and phosphorylation of an exogenous substrate is not elevated even in the presence of glial cell line-derived neurotrophic factor. Furthermore, the R833C mutation is capable of sustaining the transformed phenotype in vivo but does not confer upon the transformed cells the ability to degrade the basement membrane in a manner analogous to metastasis. Our functional characterization of the R833C substitution suggests that, like the V804M and S891A mutations, this tyrosine kinase mutation confers a weak activating potential upon RET. This is the first report demonstrating that the introduction of an intracellular cysteine can activate RET. However, this does not occur via dimerization in a manner analogous to the extracellular cysteine mutants.

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