Involvement of Dopamine Receptors in Binge Methamphetamine-Induced Activation of Endoplasmic Reticulum and Mitochondrial Stress Pathways

Single large doses of methamphetamine (METH) cause endoplasmic reticulum (ER) stress and mitochondrial dysfunctions in rodent striata. The dopamine D1 receptor appears to be involved in these METH-mediated stresses. The purpose of this study was to investigate if dopamine D1 and D2 receptors are involved in ER and mitochondrial stresses caused by single-day METH binges in the rat striatum. Male Sprague-Dawley rats received 4 injections of 10 mg/kg of METH alone or in combination with a putative D1 or D2 receptor antagonist, SCH23390 or raclopride, respectively, given 30 min prior to each METH injection. Rats were euthanized at various timepoints afterwards. Striatal tissues were used in quantitative RT-PCR and western blot analyses. We found that binge METH injections caused increased expression of the pro-survival genes, BiP/GRP-78 and P58IPK, in a SCH23390-sensitive manner. METH also caused up-regulation of ER-stress genes, Atf2, Atf3, Atf4, CHOP/Gadd153 and Gadd34. The expression of heat shock proteins (HSPs) was increased after METH injections. SCH23390 completely blocked induction in all analyzed ER stress-related proteins that included ATF3, ATF4, CHOP/Gadd153, HSPs and caspase-12. The dopamine D2-like antagonist, raclopride, exerted small to moderate inhibitory influence on some METH-induced changes in ER stress proteins. Importantly, METH caused decreases in the mitochondrial anti-apoptotic protein, Bcl-2, but increases in the pro-apoptotic proteins, Bax, Bad and cytochrome c, in a SCH23390-sensitive fashion. In contrast, raclopride provided only small inhibition of METH-induced changes in mitochondrial proteins. These findings indicate that METH-induced activation of striatal ER and mitochondrial stress pathways might be more related to activation of SCH23390-sensitive receptors

Characterisation, in vitro digestibility and expected glycemic index of commercial starches as uncooked ingredients

When selecting a native starch for specific food purposes, it is important to consider the differences between starches of varying botanical sources (cereal, tubers and roots). In this study uncooked starches as ingredients (corn, rice, wheat, tapioca and potato) were characterized according to microstructure, some (physicochemical, functional and thermal) properties, in vitro digestibility and expected glycemic index. There was a significant variation in the granule shape and size distribution of the starches, when studied using Scanning Electron Microscopy (SEM) and particle size analysis. Particle size results distinguished among starches in monomodal (corn, tapioca, potato) and bimodal (rice, wheat) populations. Among all the samples, the potato showed the biggest size distribution granules while the rice showed the lowest. The examined properties and nutritional characteristics of starches were significantly different. Thermal properties were studied by means of Differential Scanning Calorimeter (DSC). DSC studies found that the transition temperatures (58.8 °C - 78.7 °C) and enthalpies of gelatinization (2.3 J/g - 8.2 J/g) of the starches appeared to be greatly influenced by microstructure and chemical composition (e.g. resistant starch). Potato and corn starches were hydrolyzed more slowly and to a lesser extent than ones. In particular, the highest resistant starch was recorded for potato. Nutritional properties such as slowly digestible starch and expected glycemic index values followed the order: rice > wheat > tapioca >corn > potato. In general, these results provide the baseline information on the development of novel foods or native starch blends with tailored functional properties such as slow digestibility