Systemic rotenone models of Parkinson’s disease (PD) are highly reproducible and may provide evidence on the pathogenesis of PD. In the present study, male Sprague-Dawley rats (1-year-old) were subcutaneously administered with rotenone (1.5 mg/kg/day) for six days and observed for the following three weeks. Compared with the control rats, a significant decrease was observed in the body weight and a marked increase was observed in the areas under the behavioral scoring curves in the rotenone-treated rats. Immunohistochemical staining revealed that the abundance of nigral tyrosine hydroxylase (TH)-positive neurons was markedly reduced following rotenone treatment. ELISA and neurochemical assays demonstrated a significant increase in the levels of nitric oxide (NO) and NO synthase, whereas a marked decrease was observed in the thiol levels in the brains of the rotenone-treated rats. Thus, subacute rotenone treatment was found to induce behavioral deficits and the loss of nigral TH-positive neurons which may be associated with the excessive levels of NO in the rat brains.

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RNA-based vaccine represents an irresistible and safe immunization strategy with decreasing theoretical risks of genomic integration and malignant cell transformation. To our knowledge, however, there is no report about development of RNA vaccine against Toxoplasma gondii infection. We have previously demonstrated that the recombinant T. gondii nucleoside triphosphate hydrolase-II (NTPase-II) protein is able to provide protective Th1 cell-mediated immunity against T. gondii. Herein, we evaluated the immunogenic potential of a self-amplifying RNA vaccine-encoding T. gondii NTPase-II gene, RREP-NTPase-II, delivered by a synthetic lipid nanoparticle (LNP). Immunization of mice with naked RREP-NTPase-II induced a strong cellular and humoral immune response with high-IgG antibody titers and IFN-γ production. The immunized mice displayed significantly prolonged survival time and reduction in brain parasite load (46.4%) compared with control group. Furthermore, mice vaccinated with RREP-NTPase-II-encapsulated LNP displayed significantly enhanced protection against acute infection as well as chronic infection with PRU cyst, which shows 62.1% reduction in brain cyst burden in comparison to control group. These results suggest that the combination of self-amplifying RNA and LNP ion would be beneficial to the development of a safe and long-acting vaccine against toxoplasmosis.

The antisolvent precipitation method is widely applied to produce zein colloidal particles. The process involves dissolving zein in 55−90% (v/v) alcohol/water mixtures and then shearing such solutions into deionized water to lower the ethanol content. In the present work, on the basis of the preliminary result that gum arabic (GA) was able to well disperse in 70% (v/v) alcohol/water mixtures, a new way was created to produce zein−GA nanocomposites by simply mixing their aqueous alcohol solution with a high alcohol level of 70% (v/v) at pH 8.0. Findings showed that the multimodal size distribution of zein or GA alone was shifted to be the monomodal peak after zein and GA aqueous ethanol solution was mixed, indicating the successful formation of zein−GA nanocomposites. A core−shell structure was observed for zein−GA nanocomposites, with zein as a core and GA as a shell. In addition, the incorporation of GA caused the conformational and second structural changes of zein. A two-step mechanism was involved to explain the formation of zein−GA nanocomposites. The first step was that GA addition changed the polarity of zein aqueous ethanol solution and zein nanoparticles formed, and the second step was that hydrogen bonds and hydrophobic interactions promoted the adsorption of GA onto the particle surfaces. Results in this work would provide a new sight into the design of zeinbased nanocomplexes, which may have potential applications, such as constructing delivery systems, for bioactive compounds.

J. Neurochem. (2012) 120, 1072–1083. Abstract Parkinson’s disease is a chronic neurodegenerative movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. New therapeutic approaches aiming at delaying or reversing the neurodegenerative process are under active investigations. In this work, we found that harpagoside, an iridoid purified from the Chinese medicinal herb Scrophularia ningpoensis, could not only prevent but also rescue the dopaminergic neurodegeneration in MPTP/MPP+ intoxication with promising efficacy. Firstly, in cultured mesencephalic neurons, harpagoside significantly attenuated the loss of TH‐positive neuron numbers and the shortening of axonal length. Secondly, in a chronic MPTP mouse model, harpagoside dose‐dependently improved the loco‐motor ability (rotarod test), increased the TH‐positive neuron numbers in the substantia nigra pars compacta (unbiased stereological counting) and increased the striatal DAT density (125I‐FP‐CIT autoradiography). Thirdly, harpagoside markedly elevated the GDNF mRNA and GDNF protein levels in MPTP/MPP+ lesioned models. However, the protecting effect of harpagoside on the dopaminergic degeneration disappeared when the intrinsic GDNF action was blocked by either the Ret inhibitor PP1 or the neutralizing anti‐GDNF antibody. Taken together, we conclude that harpagoside attenuates the dopaminergic neurodegeneration and movement disorder mainly through elevating glial cell line‐derived neurotrophic factor.