Morphologic changes of dendritic spines of striatal neurons in the levodopa‐induced dyskinesia model

Abstract

Maladaptive plasticity at corticostriatal synapses plays an important role in the development of levodopa‐induced dyskinesia. Recently, it has been shown that synaptic plasticity is closely linked to morphologic changes of dendritic spines. To evaluate morphologic changes of dendritic spines of two types of striatal medium spiny neurons, which project to the internal segment of globus pallidus or the external segment of globus pallidus, in the levodopa‐induced dyskinesia model, we used 6‐hydroxydopamine‐lesioned rats chronically treated with levodopa. Dendritic spines were decreased and became enlarged in the direct pathway neurons of the model of levodopa‐induced dyskinesia. The same levodopa treatment to normal rats, in which no dyskinesia was observed, also induced enlargement of dendritic spines, but not a decrease in density of spines in the direct pathway neurons. These results suggest that a loss and enlargement of dendritic spines in the direct pathway neurons plays important roles in the development of levodopa‐induced dyskinesia. © 2014 International Parkinson and Movement Disorder Society

Morphological dendritic spine changes of medium spiny neurons in the nucleus accumbens in 6-hydroxydopamine-lesioned rats treated with levodopa

“…Several studies have demonstrated that the dendritic spines of medium spiny neurons (MSNs) in the CPu change their morphology in LID models (Fieblinger et al, 2014;Nishijima et al, 2014;Suarez et al, 2016;Suarez et al, 2014;Zhang et al, 2013). These morphological changes suggest maladaptive MSN excitatory synapses in the CPu.…”

“…1B). Beginning 6 weeks after the apomorphine challenge, the 6-OHDA-lesioned and sham-operated rats received 50 mg/kg levodopa methyl ester with 12.5 mg/kg benserazide, a dopa decarboxylase inhibitor (PD-Levodopa group and Control-Levodopa group), or saline (PD-Saline group and ControlSaline group), twice daily for 14 consecutive days (Nishijima et al, 2014) (Fig. 1B).…”

“…1B). To evaluate the effects of levodopa, we measured abnormal involuntary movement (AIM) scores on days 1, 4, and 11 (Nishijima et al, 2014) (Fig. 1C).…”

“…At 10 weeks of age, the rats were underwent stereotactic infusion of 6-OHDA or saline into the right medial forebrain bundle (MFB), as previously described (Nishijima et al, 2014), to create unilateral dopaminergic denervation and sham-operation animals, respectively (Fig. 1A).…”

“…Sections were dipped in DAPI (4 ,6-diamidino-2-phenylindole dihydrochloride) to stain NAc neuronal nuclei. Individual sections were prepared as previously described (Nishijima et al, 2014). MSNs in the NAc core and shell were identified according to diagrams from Paxinos's rat brain atlas ( Fig.…”