ABSTRACT
Excessive theta (θ) frequency oscillation and synchronization in the basal ganglia (BG) has been reported in elderly parkinsonian patients and animal models of levodopa (L-dopa)-induced dyskinesia (LID), particularly the θ oscillation recorded during periods when L-dopa is withdrawn (the off L-dopa state). To gain insight into processes underlying this activity, we explored the relationship between primary motor cortex (M1) oscillatory activity and BG output in LID. We recorded local field potentials in the substantia nigra pars reticulata (SNr) and M1 of awake, inattentive resting rats before and after L-dopa priming in Sham control, Parkinson disease model, and LID model groups. We found that chronic L-dopa increased θ synchronization and information flow between the SNr and M1 in off L-dopa state LID rats, with a SNr-to-M1 flow directionality. Compared with the on state, θ oscillational activity (θ synchronization and information flow) during the off state were more closely associated with abnormal involuntary movements. Our findings indicate that θ oscillation in M1 may be consequent to abnormal synchronous discharges in the BG and support the notion that M1 θ oscillation may participate in the induction of dyskinesia.
ABSTRACT
BACKGROUND UCA1 is a long non-coding RNA that has been found to be aberrantly upregulated in various cancers. The aim of this study was to determine the expression level and function of UCA1 in medulloblastoma, the most common malignant brain tumor during childhood. MATERIAL AND METHODS Real-time PCR was used to detect the expression of UCA1 in medulloblastoma specimens and cell lines. Lentiviral-mediated expression of a short hairpin RNA (shRNA) targeting UCA1 or a negative control shRNA was also achieved with the medulloblastoma cell line, Daoy. Cell proliferation and cell cycle progression were subsequently characterized with cell counting kit (CCK)-8 and flow cytometry. Cell migration was examined in wound healing and Transwell migration assays. RESULTS Levels of UCA1 mRNA were higher in the medulloblastoma specimens (p<0.05) and cell lines (p<0.05) compared to the corresponding nontumor adjacent tissue specimens and a glioblastoma cell line, respectively. For the Daoy cells with silenced UCA1, their proliferation was reduced by 30% compared to the Daoy cells expressing a negative control shRNA (p=0.017). Cell cycle arrest in the G0/G1 phase, resulting in a decreased number of cells in the S phase, as well as reduced cell migration in both wound scratch healing (p=0.001) and Transwell migration assays (p=0.021) were also observed for the Daoy cells with silenced UCA1. CONCLUSIONS UCA1 was highly expressed in part of medulloblastoma specimens and cell lines examined. In addition, knockdown of UCA1 significantly inhibited the proliferation and migration of medulloblastoma cells in vitro.
