Journal of Neural Transmission-supplement最新文献

Strategies of cell therapy for the treatment of Parkinson's disease (PD) are focused on replacing damaged neurons with cells to restore or improve function that is impaired due to cell population damage. In our studies, we used mesenchymal stromal cells (MSCs) from mouse bone marrow. Following our novel neuronal differentiation method, we found that the basic cellular phenotype changed to cells with neural morphology that express specific markers including those characteristic for dopaminergic neurons, such as tyrosine hydroxylase (TH). Intrastriatal transplantation of the differentiated MSCs in 6-hydroxydopamine-lesioned mice led to marked reduction in the amphetamine-induced rotations. Immunohistological analysis of the mice brains four months post transplantation, demonstrated that most of the transplanted cells survived in the striatum and expressed TH. Some of the TH positive cells migrated toward the substantia nigra. In conclusion, transplantation of bone marrow derived stem cells differentiated to dopaminergic-like cells, successfully improved behavior in an animal model of PD suggesting an accessible source of cells that may be used for autotransplantation in patient with PD.

The neurotoxin 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) has been reported, both in vitro and in vivo models, to produce neurodegeneration and parkinsonian symptoms after prolonged exposure in rats. The aim of the present study was to investigate the effects of TaClo on the cognitive performance of rats. We used the COGITAT hole board system where rats can find hidden pellets by exploring the board. TaClo-treated rats found as many pellets as control rats treated with saline. Furthermore, their search was as efficient as that of control animals since there were no differences between the groups regarding explorative activity, visits to non-baited holes and time needed to find the pellets. These results suggest that there is no deficit in spatial memory following the chronic administration of TaClo to rats.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in industrialized countries. Present cell culture models for PD rely on either primary cells or immortal cell lines, neither of which allow for long-term experiments on a constant population, a crucial requisite for a realistic model of slowly progressing neurodegenerative diseases. We differentiated SH-SY5Y human dopaminergic neuroblastoma cells to a neuronal-like state in a perfusion culture system using a combination of retinoic acid and mitotic inhibitors. The cells could be cultivated for two months without the need for passage. We show, by various means, that the differentiated cells exhibit, at the molecular level, many neuronal properties not characteristic to the starting line. This approach opens the possibility to develop chronic models, in which the effect of perturbations and putative counteracting strategies can be monitored over long periods of time in a quasi-stable cell population.

Isatin is an endogenous oxidized indole that influences a range of processes in vivo and in vitro. It has a distinct and discontinuous distribution in the brain and [3H]isatin binding sites are widely distributed in rat brain sections. The highest labelling is found in hypothalamic nuclei and in the cortex, hippocampus, and cerebellum (Crumeyrolle-Arias et al., 2003). However, the properties of most isatin binding sites and their physiological ligands remain unknown. In the present study the effects of three endogenous oxidized indoles (oxindole, 5-hyxdoxyoxindole, and isatin) on [3H]isatin binding were investigated in rat brain sections. In most regions cold isatin (0.2 mM) significantly reduced [3H]isatin binding. In addition to isatin, the other endogenous oxidized indoles, 5-hydroxyoxindole and oxindole were effective in displacing [3H]isatin. Total irreversible inhibition of monoamine oxidases caused inhibition of specific [3H]isatin binding in 7 of 10 brain region studied. This was accompanied by altered sensitivity of [3H]isatin binding to these indoles, including regions where a decrease of specific binding was not detected. The combinations of the three oxidized indoles produced two clear effects: augmentation (potentiation) and attenuation (blockade) of inhibitory activity compared with the independent effects of these compounds. The different effects of oxidized indoles and their combinations (isatin + 5-hydroxyoxindole and isatin + oxindole) in various brain regions therefore suggest an interaction of [(3H]isatin with different and multiple isatin-binding sites, which exhibit different sensitivity to endogenous oxidizing indoles.

Hydrogen peroxide has been shown to act as a second messenger mediating intracellular redox-sensitive signal transduction. Here we show that hydrogen peroxide is also able to transmit pro-inflammatory signals from one cell to the other and that this action can be inhibited by extracellularly added catalase. If these data can be further substantiated, hydrogen peroxide might become as important as nitric oxide as a small molecule intercellular (first) messenger.

A growing body of evidence implicates impairments in brain insulin signaling in early sporadic Alzheimer disease (sAD) pathology. However, the most widely accepted hypothesis for AD aetiology stipulates that pathological aggregations of the amyloid beta (Abeta) peptide are the cause of all forms of Alzheimer's disease. Streptozotocin-intracerebroventricularly (STZ-icv) treated rats are proposed as a probable experimental model of sAD. The current work reviews evidence obtained from this model indicating that central STZ administration induces brain pathology and behavioural alterations resembling those in sAD patients. Recently, alterations of the brain insulin system resembling those in sAD have been found in the STZ-icv rat model and are associated with tau protein hyperphosphorylation and Abeta-like aggregations in meningeal vessels. In line with these findings the hypothesis has been proposed that insulin resistance in the brain might be the primary event which precedes the Abeta pathology in sAD.

Transcranial magnetic stimulation is a tool in the neurosciences to study motor functions and nervous disorders, amongst others. Single pulses of TMS applied over the primary motor cortex lead to a so-called cortical silent period in the recording from the corresponding muscle, i.e. a period of approximately 100ms with no muscle activity. We here show that in Parkinson's disease (PD), this cortical silent period in some cases is interrupted by short bursts of EMG activity. We describe in detail these interruptions in two patients with PD. These interruptions may number up to 3 per cortical silent period and show a consistent frequency across trials and hemispheres within a given patient; the two patients described here do differ, however, in the time-delay of the interruptions and hence the induced frequency. For one patient, the frequency of the interruptions proved to be around 13 Hz, the other patient showed a frequency of around 17 Hz. The results corroborate earlier findings of cortical oscillations elicited by pulses of TMS and may be related to abnormal oscillatory activity found in the cortical-subcortical motor system in PD.

The etiology of white matter hyperintensities (WMH) seen on T2-weighted cranial magnetic resonance images is a matter of debate. We investigated deep and periventricular WMH in the brains of a community-based cohort of 532 subjects aged 75-76 years. The objective of this study was to determine whether WMH at age of 75 years were associated rather with vascular factors than with degenerative factors. Arterial hypertension treated with antihypertensive drugs favored WMH, and WMH were found more frequently in subjects with focal vascular lesions. Additionally, we found significant associations between both, deep white matter and periventricular hyperintensities, and focal atrophy of medial temporal lobe structures. The odds ratio for deep WMH in subjects with more severe medial temporal atrophy was 4.4 (95%-CI: 1.9-9.8) that for periventricular hyperintensities was 3.9 (95%-CI: 1.7-8.8). These findings might indicate that not only vascular factors alone but also degenerative factors favor the occurrence of WMH after the age of 75 years.