PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Striatal GDNF System Elicits Chemoattraction to RET Positive Dopamine Axons Seven Times Longer in Distance than the Abundant Medium Spiny Neurons and Covers Approximately One Twelfth of the Striatal Neuronal Volume
Montaño-Rodriguez, A.R.; Schorling, T.; Andressoo, J.-O. Striatal GDNF Neurons Chemoattract RET-Positive Dopamine Axons at Seven Times Farther Distance Than Medium Spiny Neurons. Cells2024, 13, 1059.
Montaño-Rodriguez, A.R.; Schorling, T.; Andressoo, J.-O. Striatal GDNF Neurons Chemoattract RET-Positive Dopamine Axons at Seven Times Farther Distance Than Medium Spiny Neurons. Cells 2024, 13, 1059.
Montaño-Rodriguez, A.R.; Schorling, T.; Andressoo, J.-O. Striatal GDNF Neurons Chemoattract RET-Positive Dopamine Axons at Seven Times Farther Distance Than Medium Spiny Neurons. Cells2024, 13, 1059.
Montaño-Rodriguez, A.R.; Schorling, T.; Andressoo, J.-O. Striatal GDNF Neurons Chemoattract RET-Positive Dopamine Axons at Seven Times Farther Distance Than Medium Spiny Neurons. Cells 2024, 13, 1059.
Abstract
Glial cell line-derived neurotrophic factor GDNF is among the strongest dopamine neuron function and survival promoting factors known. Due to this reason, it has clinical relevance in dopamine disorders such as Parkinson’s disease and Schizophrenia. In the striatum, GDNF is exclusively expressed in interneurons which make up only about 0.6% of striatal cells. Despite clinical significance, histological analysis of striatal GDNF system arborization and relevance to incoming dopamine axons, which bear its receptor RET, has remained enigmatic. This is mainly due to the lack of antibodies able to visualize GDNF and RET positive cellular processes; here we overcome this problem by using knock-in marker alleles. We find that GDNF neurons chemoattract RET+ axons at least 7 times longer in distance than medium spiny neurons (MSNs), which make up 95% of striatal neurons. Furthermore, we provide evidence that tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis, is enriched towards GDNF neurons in the dopamine axons. Finally, we find that GDNF neuron arborizations occupy approximately twelve times less striatal volume than 135 times more abundant MSNs. Collectively, our results improve our understanding of how endogenous GDNF affects striatal dopamine system function.
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.