Journal Article10.1038/373339A0
Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain
Klaus D. Beck,Janet Valverde,Tajrena Alexi,Kristian Todd Poulsen,Barbara Moffat,Richard Vandlen,Arnon Rosenthal,Franz Hefti +7 more
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TL;DR: It is reported that axotomy resulted in loss of half the tyrosine hydroxylase-expressing neurons in the substantia nigra, which suggests that GDNF or related molecules may be useful for the treatment of Parkinson's disease.
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Abstract: Glial-cell-line-derived neurotrophic factor (GDNF) promotes survival of embryonic dopaminergic neurons in culture, and its expression pattern suggests a role as a transient target-derived trophic factor for dopaminergic neurons of the substantia nigra. These neurons participate in the control of motor activity, emotional status and cognition, and they degenerate in Parkinson's disease for unknown reasons. To test whether GDNF has a trophic effect on dopaminergic neurons in the adult brain, we used a rat model in which these neurons are induced to degenerate by transecting their axons within the medial forebrain bundle. We report here that axotomy resulted in loss of half the tyrosine hydroxylase-expressing neurons in the substantia nigra. This loss was largely prevented by repeated injections of GDNF adjacent to the substantia nigra. Our findings suggest that GDNF or related molecules may be useful for the treatment of Parkinson's disease.
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References
Glial cell-line derived neurotrophic factor (GDNF) mRNA upregulation in striatum and cortical areas after pilocarpine-induced status epilepticus in rats
TL;DR: The finding of GDNF mRNA in the stimulated striatum opens the possibility that GDNF may be a target-derived, trophic factor in the nigro-striatal system and increases in GDNF RNA after status epilepticus in hippocampus and neocortex indicate additional roles for GDNF.
bFGF promotes the survival of entorhinal layer II neurons after perforant path axotomy
TL;DR: Intraventricular infusion of bFGF is capable of preventing cortical neuronal loss and/or atrophy associated with retrograde degeneration of non-cholinergic neurons following axotomy.
Regional and Cell-Specific Expression of GDNF in Rat Brain
TL;DR: A role for glial cell line-derived growth factor (GDNF) is suggested in both local and target-derived support of DA neurons, as well as potential involvement in the support of other neuronal populations in vivo.
Brain-derived neurotrophic factor administration protects basal forebrain cholinergic but not nigral dopaminergic neurons from degenerative changes after axotomy in the adult rat brain
Beat Knusel,Klaus D. Beck,JW Winslow,A Rosenthal,LE Burton,Hans Rudolf Widmer,K Nikolics,Franz Hefti +7 more
TL;DR: It is found that intraventricular administration of recombinant human BDNF (rhBDNF) to adult rats with transections of the fimbria significantly reduces axotomy-induced degenerative changes of the cholinergic cells in the basal forebrain.
Basic fibroblast growth factor in the hypoglossal system: specific retrograde transport, trophic, and lesion-related responses.
Claudia Grothe,Klaus Unsicker +1 more
TL;DR: In vivo administration of bFGF prevents lesion‐induced motoneuron death to 14% in 7 day old rats and to 60% in 18 day old Rats, but not the axotomy‐induced decrease of choline acetyltransferase activity in the hypoglossal nucleus of adult rats, consistent with a neurotrophic role ofbFGF in the Hypoglossa system.