Characterization of striatal TH-immunoreactive cells in chronic and acute L-DOPA treatment in a mice model of Parkinson?s disease

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

Berlín

Congreso; 20th International Congress of Parkinson's Disease and Movement Disorders; 2016

International Parkinson and Movement Disorder Society

Objective: To characterize Tyrosine Hydroxylase immunoreactivecells (TH-ir) in a mouse model of hemi parkinsonism and L-DOPAinduced dyskinesia.Background: L-DOPA-induced dyskinesias (LID) are a severe motorcomplication occurring frequently in Parkinson?s disease (PD) patientstreated chronically with L-DOPA (3,4-dihydroxyphenyl-l-alanine). StriatalTH expressing cells have been described in some PD patients andanimal models of PD and LID. Their presence in control animals andwhether they represent a shift in phenotype expression is still controversial.Furthermore, their ability to synthesize dopamine (DA) and theirimplication in LID remains inconclusive.Methods: C57 mice were injected with 6-hydroxydopamine (6-OHDA) or vehicle in the medial forebrain bundle and treated daily withL-DOPA or saline. In addition, a subset of 6-OHDA injected-salinetreated mice received an acute dose of L-DOPA. LID and reversal offorelimb asymmetry were assessed during treatment. Dopaminergiclesion and the presence of striatal TH-ir cells were analyzed by THimmunohistochemistry. Co-localization with c-fos was evaluated todetermine cell activity. Co-immunofluorecent stains of TH and interneuronalmarkers were performed. We conducted the same LID protocolusing a transgenic mice line expressing fluorescent green or red fluorescentproteins in Medium Spiny Neurons (MSN) that express D2 or D1receptor respectively, and we analyzed their co-localization with THexpressing cells.Results: Striatal TH-ir cells were not present in control animals or inDA depleted-vehicle treated mice. Lesioned mice treated with vehiclewho received an acute dose of L-DOPA did not show TH-ir cells either.However, they did appear in dyskinetic mice receiving a chronic treatmentwith L-DOPA and with LID development, and all of themexpressed c-fos. TH-ir cells did not co-localize with any of the interneuronalmarkers studied.Conclusions: Our findings suggest that striatal TH-ir cells are onlypresent in dyskinetic animals receiving a chronic, but not an acute doseof L-DOPA. Furthermore, we showed that these cells do not expressinterneuron markers and might be a subset of MSN that express TH after LID development in DA depleted animals. Further functional studies arerequired to elucidate if these neurons produce DA and their role afterLID development in DA depleted animals. Further functional studies arerequired to elucidate if these neurons produce DA and their role afterDA denervation and pharmacological DA replacement.