Spearman's rank correlation coefficient (r_s) and <i>P</i> values between Hcy and clinical variables, and between CRP and clinical variables.

<p>* <i>P</i><0.05,</p><p>** <i>P</i><0.01,</p><p>*** <i>P</i><0.001.</p><p>Abbreviations: r_s, Spearman's rank correlation coefficient; H&Y, the modified Hoehn and Yahr staging scale; MMSE, mini-mental state examination.</p

Comparison of age, BMI, Hcy, CRP, UPDRS (III), MMSE, and NMSS between PD and VP.

<p>* <i>P</i><0.01.</p><p>Abbreviations: SD, Standard deviation; BMI, Body Mass Index; MMSE, mini-mental state examination; UPDRS III, the unified Parkinson's disease rating scale part III; and NMSS, non-motor symptoms scale for Parkinson's disease (range of possible scores from 0 to 360).</p

Demographic, motor, and non-motor parameters.

<p>Abbreviations: SD, Standard deviation; BMI, Body Mass Index; MMSE, mini-mental state examination; UPDRS III, the unified Parkinson's disease rating scale part III; H&Y, the modified Hoehn and Yahr staging scale; and NMSS, non-motor symptoms scale for Parkinson's disease (range of possible scores from 0 to 360).</p

Spearman's rank correlation coefficient (r_s) and <i>P</i> values between UPDRS III and clinical variables, and between H&Y and clinical variables.

<p>* <i>P</i><0.05,</p><p>** <i>P</i><0.001.</p><p>Abbreviations: r_s, Spearman's rank correlation coefficient; H&Y, the modified Hoehn and Yahr staging scale; UPDRS III, the unified Parkinson's disease rating scale part III; MMSE, mini-mental state examination; NMSS, non-motor symptoms scale for Parkinson's disease.</p

Comparison of Hcy and CRP among patients with PD and VP.

<p>* <i>P</i><0.01</p

Figure 2

<p><b>2A.</b>[³H] MK-801 autoradiography depicts the expression of NMDA receptors in the rat brain. The maps of A, B and C are adopted from a rat brain atlas indicating the levels where the [³H]MK-801 binding density was measured. Autoradiographs (D, E, F) and (D', E', F') depict the expression of [³H]MK-801 binding and non-specific [³H]MK-801 binding at different rostro-caudal coronal levels of the rat brain. <b>2B.</b> Typical autoradiographs depict the expression of NMDA receptors in the hippocampus (Hipp) and amygdala (Amy) among control, 6-OHDA-lesioned rats, and 6-OHDA lesioned rats that also received simvastatin treatment. The bar chart shows the effects of chronic simvastatin treatment on [³H]MK-801 binding in the different groups of rat brain regions. <i>Note</i>: Units of measurement are in nCi/mg tissue. Data are means ± SEM. Asterisks indicate significant differences from control group (saline) and cross indicates significant differences between 6-OHDA rats and 6-OHDA with simvastatin-treated rats (n = 6–8, **p<0.01; ***p<0.001; †p<0.05; ††p<0.01; †††p<0.001, one-way ANOVA followed by Tukey's test).</p

Figure 3

<p><b>3A.</b>Simvastatin ameliorates the anxiety of 6-OHDA rats in the EPM test. The graph shows the ratio of time spent in the open arms to total time and the ratio of open arm entries to total entries in the EPM. The parameters are expressed as a percentage of time spent in the open arms to the total time and open arm entries to total entries in the EPM. The values represent mean ± SEM, n = 6–8. †p<0.05, 6-OHDA group versus 6-OHDA+simvastatin group for open arm duration; ***p<0.001, 6-OHDA group versus control group for open arm duration; *p<0.05, 6-OHDA group versus control group for open entires. <b>3B.</b> Correlations between duration in the open arm of EPM and [³H]MK-801 binding density in brain regions. A significant positive correlation was identified between the [³H]MK-801 binding density in the hippocampus (r = 0.485 Pearson's correlation, p = 0.026), amygdala (r = 0.622, p = 0.003), CA1 (r = 0.638, p = 0.002), respectively, and the time spent in the open arm of the EPM.</p

6-OHDA increased synaptic cluster density and number of clusters NR1 receptors and TNF-a, and the upregulation was abolished after simvastatin treatment.

<p>Arrows in <b><i>I, J, K</i></b> indicate nuclear, TNF-a, and NR1, respectively. PC12 cultures double-labeled for NR1 (red, <b><i>C,G,K</i></b>) and TNF-a (green, <b><i>B,F,J</i></b>); Hoechst 33342 indicates nuclear staining (blue, <b><i>A, E, I</i></b>). 6-OHDA treatment significantly increased the density of NR1 (<b><i>G</i></b>) and TNF-a clusters (<b><i>F</i></b>), and the elevated density was abolished by simvastatin treatment (<b><i>K, J</i></b> for NR1 and TNF-a, respectively). A significant difference in the density of NR1 and TNF-a was observed among control, 6-OHDA, and 6-OHDA+sim groups (<i>p</i><0.05, control <i>vs</i> 6-OHDA; <i>p</i><0.05, 6-OHDA <i>vs 6-OHDA</i>+sim; <i>n</i> = 9–12; Student's <i>t</i> test). All the results are expressed as means ± standard error of the mean. Scale bars: 100 µm.</p

Effects of 6-OHDA lesion and simvastatin on TH immunohistochemistry staining in the SNpc.

<p>Figs. A, B, C shows TH staining in low-power photomicrograph in the SNpc of unlesioned, 6-OHDA-lesioned, and 6-OHDA-lesioned with simvastatin treatment groups, respectively. Bar = 450 µm. Figs. D, E, F shows TH staining at higher magnification photomicrograph in the SNpc of unlesioned, 6-OHDA-lesioned, and 6-OHDA-lesioned with simvastatin treated groups, respectively. Bar = 120 µm. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020945#pone-0020945-g001" target="_blank">Fig. 1G</a> represents the average number of TH-positive dopaminergic neurons in the SNpc of unlesioned (control), 6-OHDA lesioned, and 6-OHDA lesioned with simvastatin treatment groups. The values represent mean ±SEM, n = 6–8. ***p<0.001, 6-OHDA group versus control group; ††† p<0.001, 6-OHDA+simvastatin group versus 6-OHDA group.</p

Simvastatin reduced 6-OHDA medicated elevations of NMDANR1 receptors, TNF-a, and MMP9.

<p>6-OHDA incubation pronouncedly increased the NR1 receptors compared with controls (***p<0.001, 6-OHDA <i>vs</i> controls, n = 6–9); while this elevation was significantly abolished following simvastatin treatment (†††p<0.001, 6-OHDA <i>vs</i> 6-OHDA+sim, n = 6–9). Compared with controls, 6-OHDA produced significant increases in the total amount of TNF-a and MMP9 (***p<0.001, 6-OHDA <i>vs</i> controls, n = 6–9); while these increases were prevented by simvastatin treatment (†††p<0.001, 6-OHDA <i>vs</i> 6-OHDA + sim, n = 6–9). All the results are expressed as mean ± standard error of the mean.</p