Dopaminergic striatal innervation predicts interlimb transfer of a visuomotor skill

We investigated whether dopamine influences the rate of adaptation to a visuomotor distortion and the transfer of this learning from the right to the left limb in human subjects. We thus studied patients with Parkinson disease as a putative in vivo model of dopaminergic denervation. Despite normal adaptation rates, patients showed a reduced transfer compared with age-matched healthy controls. The magnitude of the transfer, but not of the adaptation rate, was positively predicted by the values of dopamine-transporter binding of the right caudate and putamen. We conclude that striatal dopaminergic activity plays an important role in the transfer of visuomotor skills.     

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

Iodothyronines influence lipid metabolism and energy homeostasis. Previous studies demonstrated that 3,5-l-diiodothyronine (T(2)), as well as 3,3',5-L-triiodothyronine (T(3)), was able to both prevent and reverse hepatic steatosis in rats fed a high-fat diet, and this effect depends on a direct action of iodothyronines on the hepatocyte. However, the involvement of thyroid hormone receptors (TRs) in mediating the lipid-lowering effect of iodothyronines was not elucidated. In this study, we investigated the ability of T(2) and T(3) to reduce the lipid overloading using the rat hepatoma FaO cells defective for functional TRs. The absence of constitutive mRNA expression of both TRα1 and TRβ1 in FaO cells was verified by RT-qPCR. To mimic the fatty liver condition, FaO cells were treated with a fatty acid mixture and then exposed to pharmacological doses of T(2) or T(3) for 24 h. Lipid accumulation, mRNA expression of the peroxisome proliferator-activated receptors (PPAR-α, -γ, -δ) the acyl-CoA oxidase (AOX), and the stearoyl CoA desaturase (SCD1), as well as fuel-stimulated O(2) consumption in intact cells, were evaluated. Lipid accumulation was associated with an increase in triacylglycerol content, PPARγ mRNA expression, and a decrease in PPARδ and SCD1 mRNA expression. The addition of T(2) or T(3) to lipid-overloaded cells resulted in i) reduction in lipid content; ii) downregulation of PPARα, PPARγ, and AOX expression; iii) increase in PPARδ expression; and iv) stimulation of mitochondrial uncoupling. These data demonstrate, for the first time, that in the hepatocyte, the lipid-lowering actions of both T(2) and T(3) are not mediated by TRs.     

Hyperhomocysteinemia in levodopa‐treated patients with Parkinson's disease dementia

Dementia is a frequent non‐motor feature of Parkinson's disease (PD). Elevated plasma homocysteine (Hcy) levels have been associated with both cognitive impairment and dementia. Increased Hcy levels have been observed in levodopa‐treated patients with PD. The objective of our study was to evaluate the association between plasma Hcy levels and dementia in PD. We performed a multicenter cross‐sectional study on patients with PD with (PDD) and without (PDnD) dementia and age‐ and sex‐matched healthy controls. We compared Hcy levels in patients with PDD and PDnD and healthy controls, and we performed logistic regression analysis to search for an association between the presence of dementia and increased Hcy levels in PD. Patients with PD (121), PDD (42), and PDnD (79), and age‐ and sex‐matched controls (154) were enrolled. Hcy levels were higher in patients with PD compared to controls (17.5 μmol/L ± 10.2 vs. 11 ± 4.1; P < 0.00001). Among patients with PD, Hcy levels were higher in the PDD group compared to the PDnD group (20.7 μmol/L ± 12.1 vs. 15.8 ± 8.5; P = 0.002). In a multivariate logistic regression model, higher Hcy levels [Odds ratios comparing the top (>18.9 μmol/L) with the bottom tertile (<12.4 μmol/L): 3.68; 95% CI: 1.14–11.83] were significantly associated with dementia. These data support the association between elevated Hcylevels and the presence of dementia in PD. © 2009 Movement Disorder Society     

Bisphenol-A alters gene expression and functional parameters in molluscan hepatopancreas

Bisphenol-A (BPA) is a well-known xenoestrogen in mammalian systems that can affect reproduction also in aquatic organisms. In this work the possible effects of BPA were investigated in the hepatopancreas of the bivalve mollusc Mytilus galloprovincialis: mussels were injected with different amounts of BPA (3-60ng/g dw tissue) and tissues sampled at 24h post-injection. Expression of different Mytilus genes was evaluated by RT-Q-PCR: BPA exposure increased the expression of MeER2 and induced downregulation of antioxidant genes, catalase and metallothioneins. Moreover, BPA induced changes in activity of catalase, GSH transferase (GST) and GSSG reductase (GSR), and in total glutathione content. A decrease in lysosomal membrane stability and increased neutral lipid accumulation were also observed. The results were compared with those obtained with similar concentrations of 17beta-estradiol. These data demonstrate that BPA can alter gene expression, activities of enzymes involved in redox balance, and lysosomal function in molluscan hepatopancreas, a tissue involved in the control of metabolism and gamete maturation. Overall, these data indicate that BPA, at environmentally relevant concentrations, can have both estrogen-like and distinct effects in invertebrates like in vertebrates.