Characterization of striatal Tyrosine Hydroxylase-immunoreactive (TH-ir) cells in chronic and acute L-DOPA treatment in a mice model of Parkinson´s disease.

GOMEZ G; SANZ BLASCO S; MURER MG; BORDONE M; FERRARIO JE; GERSHANIK OS; BERNARDI MA; TARAVINI IR

Buenos Aires

Congreso; 2nd FALAN Congress (Federation of Latin American and Caribbean Neuroscience Societies); 2016

Sociedad Argentina de Investigación en Neurociencias

L-DOPA-induced dyskinesia (LID) are a frequent severe complication in Parkinson?s Disease (PD) patients treated chronically with L-DOPA (3,4-dihydroxyphenyl-l-alanine). Striatal TH-ir cells have been described in PD patients and animal models of PD and LID. Their presence in control animals and if they represent a shift in phenotype expression is still controversial. C57 mice were injected with 6-hydroxydopamine (6-OHDA) or vehicle in the medial forebrain bundle, and treated daily with L-DOPA or saline. In addition, a subset of 6-OHDA mice received an acute dose of L-DOPA. LID were assessed during treatment, and dopaminergic lesion and the presence of striatal TH-ir cells were analyzed by immunohistochemistry. Striatal TH-ir cells were not present in control animals or in 6-OHDA/saline treated mice or in mice that received an acute dose of L-DOPA. However, they did appear in mice treated chronically with L-DOPA. Co-localization with c-fos showed that all of them expressed c-fos. We performed co-immunostains for TH and interneuron markers and we found no co-localization. Finally, we conducted the same LID protocol using a transgenic mice line expressing green or red fluorescent proteins in Medium Spiny Neurons (MSN) that express D2 or D1 receptor. TH-immunofluorescence revealed that TH is not expressed by any of these two populations of MSN. Further studies are required to fully characterize TH-ir cells and their role after DA denervation and pharmacological DA replacement.