Striatal GDNF Neurons Chemoattract RET-Positive Dopamine Axons at Seven Times Farther Distance Than Medium Spiny Neurons.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Glial Cell Line-Derived Neurotrophic Factor*/metabolism ; Axons*/metabolism ; Corpus Striatum*/metabolism ; Corpus Striatum*/cytology ; Proto-Oncogene Proteins c-ret*/metabolism ; Proto-Oncogene Proteins c-ret*/genetics ; Dopaminergic Neurons*/metabolism; Animals ; Mice ; Dopamine/metabolism ; Tyrosine 3-Monooxygenase/metabolism ; Mice, Inbred C57BL ; Neurons/metabolism ; Medium Spiny Neurons

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 seven times farther 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 only 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.

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297727 Academy of Finland; 350678 Academy of Finland; 352077 ERA-NET NEURON; 2019-01578 Swedish Research Council; 2022-01093 Swedish Research Council; 724922 International ERC_ European Research Council

Keywords: GDNF; RET; chemoattraction; dopamine; neurotrophic factors; parvalbumin

0 (Glial Cell Line-Derived Neurotrophic Factor)
EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
VTD58H1Z2X (Dopamine)
EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
EC 2.7.10.1 (Ret protein, mouse)

Date Created: 20240626 Date Completed: 20240626 Latest Revision: 20240628

20240628

PMC11202212

10.3390/cells13121059

38920687