The role of the laterodorsal nucleus of the thalamus in spatial learning and memory in the rat

The anterior thalamic nuclei appear to play an important role in learning and memory. Connectionally and structurally, the lateral dorsal nucleus is similar to the anterior nuclei. This study tested the hypothesis that the laterodorsal thalamic nucleus (LD) also contributes to these functions. Adult Sprague-Dawley rats received bilateral ibotenic acid lesions of LD, and 2 weeks later the rats were tested in a repeated acquisition water maze task. The control groups displayed a short final escape latency and showed a preference for the correct quadrant in the probe trial. Rats with a lesion restricted to LD (LDL) were mildly impaired in the task, but rats with lesions that destroyed LD and also significantly (50%) damaged the adjacent anterior thalamic nuclei (LDL+) were severely impaired, displaying no improvement in performing the spatial task. In a second experiment, training in the same paradigm for 2 weeks resulted in improved final performance by LDL and control rats but not by LDL+ rats. These findings support the hypothesis that together with the anterior thalamic nuclei, LD plays a role in spatial learning and memory.     

Substance P receptor antagonists in psychiatry: rationale for development and therapeutic potential

Increasing evidence suggests that substance P (SP) and its receptor (neurokinin [NK]-1 receptor [NK1R]) might play an important role in the modulation of stress-related, affective and/or anxious behaviour. First, SP and NK1R are expressed in brain regions that are involved in stress, fear and affective response (e.g. amygdala, hippocampus, hypothalamus and frontal cortex). Second, the SP content in these areas changes upon application of stressful stimuli. Third, the central administration of SP produces a range of fear-related behaviours. In addition, the SP/NK1R system shows significant spatial overlap with neurotransmitters such as serotonin and noradrenaline (norepinephrine), which are known to be involved in the regulation of stress, mood and anxiety. Therefore, it was hypothesised that blockade of the NK1R might have anxiolytic as well as antidepressant effects.Preclinical studies investigating the effects of genetic or pharmacological NK1R inactivation on animal behaviour in assays relevant to depression and anxiety revealed that the behavioural changes resemble those seen with reference antidepressant or anxiolytic drugs. Furthermore, antagonism or genetic inactivation of the NK1R causes alterations in serotonin and norepinephrine neuronal transmission that are likely to contribute to the antidepressant/anxiolytic activity of NK1R antagonists but that are--at least partially--distinct from those produced by established antidepressant drugs. This underlines the conceivable unique mechanism of action of this new class of compounds. In three independent clinical trials with three different compounds (aprepitant [MK-869], L-759274 and CP-122721), an antidepressant effect of NK1R antagonists could be demonstrated. These results, however, have been challenged by recent failed studies with aprepitant.There are numerous indications from preclinical studies that, in addition to SP and NK1R, other neurokinins and/or neurokinin receptors might also be involved in the modulation of stress-related behaviour and that exclusive blockade of the NK1R might not be sufficient to produce consistent anxiolytic and antidepressant effects. One such candidate is the neurokinin-2 receptor (NK2R), and clinical trials to assess the antidepressant effects of NK2R antagonists are currently underway. Of special interest might also be substances that block more than one receptor type such as NK1/2R antagonists or NK1/2/3R antagonists. These compounds may be more efficacious in antagonising the effects of SP than compounds that only block the NK1R.     

Quantitative single-voxel spectroscopy: the reciprocity principle for receive-only head coils

PURPOSE: To correct MR spectra for local changes in the coil sensitivity for a widely used coil setup, consisting of a transmitting body coil and a receive-only head coil. MATERIALS AND METHODS: The method relies on the reciprocity principle for the body coil and a correction factor for signal amplitudes between body coil and head coil. The correction is based either on the local flip angle dependence of the stimulated echo acquisition mode signal (TFC) or on the automatic RF calibration (RFC). Water phantoms of different volumes were used to simulate variable coil loads, and B1 field inhomogeneities were assessed by varying the voxel position. Furthermore, the correction was tested by longitudinal measurements in one volunteer. RESULTS: The correction in vitro yields a reduction of the variation coefficient of the water signal by about 77% (TFC) and 66% (RFC) for different coil loads, as well as 55% (TFC) for variable voxel positions. Slightly lower reductions were assessed for the variation coefficients of the metabolite signals in vivo. CONCLUSION: This approach adequately compensates for local changes in coil sensitivity, when acquiring MR spectra with a receive-only head coil.     

Multidrug-resistant tuberculosis detection, Latvia

To improve multidrug-resistant tuberculosis (MDR-TB) detection, we successfully introduced the rpoB gene mutation line probe assay into the national laboratory in Latvia, a country with epidemic MDR-TB. The assay detected rifampin resistance with 91% sensitivity and 96% specificity within 1 to 5 days (vs. 12-47 days for BACTEC).     

Does electroconvulsive therapy (ECT) affect cognitive components of auditory evoked P300?

Electroconvulsive therapy (ECT), as a treatment tool for psychiatric disorders, is believed to be safe and effective. Nevertheless, it has a negative impact on cognitive functioning, especially on memory, causing both retrograde and anterograde amnesia. However, ECT effects on more subtle stages of information processing are not studied enough. Event-related potentials, and especially P300, are thought to reflect physiology of cognition. Thus, we aimed to evaluate the effects of ECT treatment on parameters of endogenous components (N2, P3) of the P300 potential. Seventeen patients suffering from schizophrenia, schizoaffective disorder and recurrent depressive disorder participated at the study. After the course of ECT, significant increase of N2 amplitude in parietal midline region and prolongation of P3 latency in frontal midline region, of which the magnitude positively correlated with the number of ECT procedures, have been obtained.     

Effects of psycho-social stress during pregnancy on neuroendocrine and behavioural parameters in lactation depend on the genetically determined stress vulnerability

The neuroendocrine consequences of repeated exposure of the pregnant mother to relevant stressors have been studied in the offspring, but not in the mothers. As these stress effects might depend on the genetically determined stress susceptibility of the dams, here, we investigated the effects of daily exposure to psycho-social stressors (maternal defeat by an aggressive lactating resident and restraint) between pregnancy days 4 and 18 in female rats selectively and bidirectionally bred for high (HAB) or low (LAB) anxiety-related behaviour. ACTH and corticosterone secretory responses to a mild stressor were found to be low in unstressed lactating HAB and LAB dams (day 8 of lactation) indicating an intact physiological attenuation of the HPA axis at this time. Pregnancy stress significantly increased the reactivity of the hypothalamo-pituitary-adrenal (HPA) axis in lactating HAB, but not LAB rats, reflecting impaired attenuation of the HPA axis selectively in pregnancy-stressed HAB dams. The high and low anxiety phenotypes were consistent in lactation and not significantly altered by pregnancy stress, despite an elevated level of arousal in pregnancy-stressed HAB dams. In general, HAB dams showed signs of a more protective maternal behaviour compared to LAB dams: (i) in the home cage, HAB dams spent more time in direct pup contact (day 1 of lactation), (ii) during two forms of the pup retrieval test, differing in the level of challenging the dam, HAB dams retrieved the pups faster, and (iii) during the maternal defence test, they were more aggressive towards a virgin intruder compared to LAB and NAB dams. Pregnancy stress did not alter any of these behavioural measures, except an increase in the speed of pup collection in a novel environment in HAB dams and increased maternal aggression in LAB dams. The results indicate a robust behavioural phenotype of HAB and LAB dams with respect to anxiety and maternal behaviour which was found to be almost unchanged by exposure to pregnancy stress. However, the finding of differential effects of pregnancy stress on the attenuation of the reactivity of the HPA axis in lactation makes HAB and LAB rats a potential animal model for studying genetically determined differences in stress vulnerability and stress-induced maladaptation of the HPA axis post-partum.     

Plasminogen activities and concentrations in patients with sporadic Creutzfeldt-Jakob disease

Human plasminogen has been shown to interact with the abnormal disease-specific prion protein. Till now, no data are available for patients with Creutzfeldt-Jakob disease (CJD). Therefore, we compared plasminogen concentrations and plasminogen activities in patients with sporadic CJD and controls with other dementia, which were collected in the framework of the German CJD Surveillance study. Patients with CJD had significantly higher plasminogen concentrations than patients with other forms of dementia and plasminogen specific activities were lower in CJD patients. The reasons for these abnormalities are not clear at the moment. The results may reflect a disease-specific prion protein and plasminogen interaction in patients with CJD. Other possible explanations are plasminogen polymorphisms and genotypes with distinct plasminogen activity levels in CJD than in controls, which should be a subject for further studies.