Occlusal disharmony induces BDNF level in rat submandibular gland

Objectives: Brain-derived neurotrophic factor (BDNF), which is produced in rat submandibular gland, is one of the most abundant neurotrophins in the central nervous system. It is generally accepted that occlusal disharmony causes stress. The purpose of the present study was to investigate whether occlusal disharmony-induced chronic stress affects BDNF levels and morphology in rat submandibular gland. Design: Eight wks old male Wistar rats (n = 21) were randomly divided into three groups of 7 rats. In a control (C) group, the rats received no treatment for 8 wks. In a molar cusp-less (OD) group, maxillary molar cusps were cut off with a dental turbine at baseline and kept for 8 wks. In a molar cusp-less + recovered cusp (OR) group, maxillary molar cusps were cut off and then were recovered after 4 wks using resin material. After the experimental period, expression of BDNF mRNA and protein as well as histological findings were evaluated in the submandibular glands. The comparisons between the groups were made using the Mann-Whitney U test with Bonferroni correction. Results: The OD group showed a significant increase in submandibular gland BDNF mRNA and protein expression after 8 wks, and plasma adrenocorticotropic hormone and corticosterone levels increased in a time-dependent manner. There were no significant differences in BDNF expression in the submandibular glands and in levels of plasma adrenocorticotropic hormone and corticosterone between the OR and C groups. Conclusions: These results indicate that psychological stress induced by occlusal disharmony reversibly induces BDNF expression in the rat submandibular gland

A Single Subcutaneous Injection of Cellulose Ethers Administered Long before Infection Confers Sustained Protection against Prion Diseases in Rodents

Prion diseases are fatal, progressive, neurodegenerative diseases caused by prion accumulation in the brain and lymphoreticular system. Here we report that a single subcutaneous injection of cellulose ethers (CEs), which are commonly used as inactive ingredients in foods and pharmaceuticals, markedly prolonged the lives of mice and hamsters intracerebrally or intraperitoneally infected with the 263K hamster prion. CEs provided sustained protection even when a single injection was given as long as one year before infection. These effects were linked with persistent residues of CEs in various tissues. More effective CEs had less macrophage uptake ratios and hydrophobic modification of CEs abolished the effectiveness. CEs were significantly effective in other prion disease animal models; however, the effects were less remarkable than those observed in the 263K prion-infected animals. The genetic background of the animal model was suggested to influence the effects of CEs. CEs did not modify prion protein expression but inhibited abnormal prion protein formation in vitro and in prion-infected cells. Although the mechanism of CEs in vivo remains to be solved, these findings suggest that they aid in elucidating disease susceptibility and preventing prion diseases

CE effects on PrP expression and PrP^Sc formation.

<p>(a) Immunoblotting of PrP^C in the brain and spleen from Tg7 mice treated with TC-5RW (4 g/kg body weight) or vehicle at the designated time points (<i>n</i> = 3 for each time point). Molecular size markers on the right indicate sizes in kDa. The mean and standard deviation are shown in each bar graph. (b) PrP mRNA expression level in the brain and spleen from Tg7 mice treated with TC-5RW (4 g/kg body weight) or vehicle at designated time points. The mean and standard deviation (<i>n</i> = 3 for each time point) are shown. (c) Immunoblotting of protease-resistant PrP^Sc in the protein misfolding cyclic amplification reaction performed in the presence of TC-5RW. Representative quadruplicate data are shown for the cyclic amplification of 263K prion performed in the presence (+) or absence (−) of TC-5RW or hydroxypropyl methyl dextran-70 kDa (HP-M-dextran-70) at a dose of 10 μg/mL. HP-M-dextran-70 was used as a negative control. In the absence of each compound, the vehicle, water, was added to the reaction mixture. (d) Immunoblotting of protease-resistant PrP^Sc in RML prion-infected N2a cells treated with HPMCs. Signals for β-actin are shown as controls for the integrity of samples used for PrP^Sc detection. The chemical property and <i>in vivo</i> efficacy of TC-5EW are shown in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006045#ppat.1006045.s004" target="_blank">S4 Fig</a>. (e) Immunoblotting of PrP^C in uninfected N2a cells treated with HPMCs at a dose of 1 mg/mL in duplicate. (f) Flow cytometry of cell surface PrP^C in uninfected N2a cells treated with HPMCs at a dose of 1 mg/mL. Black and blue lines indicate vehicle-treated cells and HPMC-treated cells, respectively. The broken line peaks on the left show the respective isotype controls.</p

Structure–activity study of CEs.

<p>(a)Chemical summary of SM-4 derivatives tested in the study. (b) Survival of intracerebrally 263K prion-infected Tg7 mice treated with SM-4 derivatives. A single subcutaneous injection (2 g/kg body weight) was given at 1 dpi.</p