Opening of the mitochondrial membrane permeability transition pore (MPTP) is an important factor in the activation of apoptotic and necrotic processes in mammalian cells. In a previous paper we have shown that cardiac mitochondria from neonatal rats are more resistant to calcium load than mitochondria from adult animals. In this study we have analyzed the ontogenetic development of this parameter both in heart and in liver mitochondria. We found that the high resistance of heart mitochondria decreases from day 14 to adulthood. On the other hand, we did not observe a similar age-dependent sensitivity in liver mitochondria, particularly in the neonatal period. Some significant but relatively smaller increase could be observed only after day 30. When compared with liver mitochondria cardiac mitochondria were more resistant also to the peroxide activating effect on calcium-induced mitochondrial swelling. These data thus indicate that the MPTP of heart mitochondria is better protected against damaging effects of the calcium load and oxidative stress. We can only speculate that the lower sensitivity to calcium-induced swelling may be related to the higher ischemic tolerance of the neonatal heart., Z. Drahota, ... [et al.]., and Obsahuje seznam literatury
The present review brings the survey of the most frequently used behavioural tests in experimental models of Parkinson's disease (PD). Although there is no spontaneous occurrence of parkinsonism in animals, several experimental animal models of PD have been developed to achieve the same clinical features in animals. The techniques employing neurotoxins in lesioning the nigrostriatal dopaminergic (DA) system have a large selectivity and reproducibility. The most frequently used neurotoxins are l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA). MPTP-lesioned monkeys mimic best the symptomatology of PD in human patients while rats appear to be refractory to MPTP. For that reason, 6-OHDA is used to damage the substantia nigra in a rodent model. Behavioural tests of animals with nigrostriatal lesion represent valuable non- invasive methods for assessing the influence of damaged DA system on locomotor activity. The most frequently used experimental model of PD is the drug-evoked rotation in 6-OHDA unilaterally lesioned rats. This model produces well-defined and stable behavioural deficits. The rotation test is a useful parameter for evaluating imbalances of dopamine in both striata of the hemi-parkinsonian rat model. T-maze, treadmill running test or sensorimotor tests are used to evaluate spontaneous locomotor activity of lesioned animals. Skilled motor tasks measure the influence of dopamine-depleting lesions on complex motor acts. Transplantation of DA tissue into the striatum offers a new approach to the treatment of PD. Experimental models and behavioural tests are used to evaluate the extent of graft-induced recovery of MPTP- or 6-OHDA-lesioned animals. Different results obtained after the use of different tests reflect the level of graft integration into the host circuitry.
Erythropoietin (EPO), known for its role in erythroid differentiation, has been suggested to have a direct protective role against a variety of neurotoxic insults. In the present study, we investigated the expression of EPO receptor (EPOR) and the number of EPORpositive cells in three encephalic regions (ventral mesencephalon, striatum, cortex) following lesion induced by 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP). C57BL/6 mice underwent intraperitoneal injection of MPTP at 24 h intervals for 5 days, and their brains were examined 1, 2, 4, 7, 14 or 21 days after the last injection. Western blot and immunohistochemistry analysis revealed that EPOR was dramatically up-regulated in the ventral mesencephalon, 4 days after MPTP insult until the day 21. In contrast, there was a baseline level of EPOR in the striatum and cortex. At subsequent time points after MPTP injury, the levels of EPOR in the two regions were not statistically different compared with those in normal animals. These results suggest that the regional specific up-regulation of EPOR at an early stage after MPTP stimulus may represent a pro-survival mechanism against neurotoxin injury in Parkinsonian model., Y. Wu ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The acute and chronic effect of l-methyl-4-plicnyl-l,2,3,6- tetrahydropyridine (MPTP) on spontaneous motor activity and its development was studied in chick embryos. 1. From the 13th day of incubation, the acute effect of MPTP (30 mg/kg e.w., up to 60 min after administration) consisted in significant depression of spontaneous motility. From the 17th day, the effect of MPTP in supraspinal compartments of the CNS also began to participate in this depression. 2. Flic subacute effect of MPTP (up to 24 h after a single dose) was lethal for 11-day-old embryos. Conversely, in older embryos resting motility partly recovered, with signs of an inverse correlation to the embryo’s age. The final effect, however, consisted in absolute failure of the hatching process. 3. The chronic effect of MPTP (3.57 mg/kg e.w./24 h, from the 4th to the 16th day of incubation) led to a developmental reduction of spontaneous motor activity, chiefly from the 8th to 12th day of incubation. 4. The interaction of nialamide (25 mg/kg e.w.), a blocker of monoaminooxidasc produced disparate results with the effect of MPTP in young and old embryos.