Biomedical subjects

Mária Simon

Publications and source records attributed to Mária Simon.

8 recordsLinked to original sources

PubMed2006

NK1 receptor antagonists under investigation for the treatment of affective disorders.

Substance P-neurokinin-1 (NK1) receptor pathways have been repeatedly implicated in the pathophysiology of affective disorders. Anatomical studies in humans have shown a high expression of NK1 receptors in brain regions that are important for the regulation of affective behaviours and stress responses. A large body of evidence that has been generated from animal experiments indicates that treatment with a selective NK1 receptor antagonist might be effective in the treatment of certain forms of anxiety and depressive disorders. Accordingly, numerous NK1 receptor antagonists have either been synthesised and are under clinical development, or have already been tested in clinical trials. However, the initial encouraging clinical results were followed by repeated demonstrations of a lack of effectiveness, thus disappointment and doubt currently surrounds the idea that these compounds may become effective antidepressants. Research continues and novel molecules may show better pharmacokinetic and pharmacodynamic properties and, therefore, may achieve therapeutic success. Furthermore, NK1 receptor antagonists that are ineffective in the treatment of mood disorders may still prove to be effective in the treatment of anxiety problems.

Animals↗

PubMed2005

Astroglial plasticity in the hippocampus is affected by chronic psychosocial stress and concomitant fluoxetine treatment.

Analysis of post-mortem tissue from patients with affective disorders has revealed a decreased number of glial cells in several brain areas. Here, we examined whether long-term psychosocial stress influences the number and morphology of hippocampal astrocytes in an animal model with high validity for research on the pathophysiology of major depression. Adult male tree shrews were submitted to 5 weeks of psychosocial stress, after which immunocytochemical and quantitative stereological techniques were used to estimate the total number and somal volume of glial fibrillary acidic protein-positive astrocytes in the hippocampal formation. Stress significantly decreased both the number (-25%) and somal volume (-25%) of astroglia, effects that correlated notably with the stress-induced hippocampal volume reduction. Additionally, we examined whether antidepressant treatment with fluoxetine, a selective serotonin reuptake inhibitor, offered protection from these stress-induced effects. Animals were subjected to 7 days of psychosocial stress before the onset of daily oral administration of fluoxetine (15 mg/kg per day), with stress continued throughout the 28-day treatment period. Fluoxetine treatment prevented the stress-induced numerical decrease of astrocytes, but had no counteracting effect on somal volume shrinkage. In nonstressed animals, fluoxetine treatment had no effect on the number of astrocytes, but stress exposure significantly reduced their somal volumes (-20%). These notable changes of astroglial structural plasticity in response to stress and antidepressant treatment support the notion that glial changes may contribute to the pathophysiology of affective disorders as well as to the cellular actions of antidepressants.

Animals↗

PubMed2005

Age-dependent susceptibility of adult hippocampal cell proliferation to chronic psychosocial stress.

Stress inhibits neurogenesis in the adult dentate gyrus. It is not known, however, whether age has any influence on this process. We subjected adult male tree shrews to 5 weeks of psychosocial stress, after which dentate cytogenesis was determined using BrdU immunohistochemistry. We found that older animals were significantly more vulnerable to the adverse effect of stress on dentate cell proliferation.

Adrenal Glands↗

PubMed2005

Examining SLV-323, a novel NK1 receptor antagonist, in a chronic psychosocial stress model for depression.

RATIONALE: Substance P antagonists have been proposed as candidates for a new class of antidepressant compounds. OBJECTIVES: We examined the effects of SLV-323, a novel neurokinin 1 receptor (NK1R) antagonist, in the chronic psychosocial stress paradigm of adult male tree shrews. METHODS: Animals were subjected to a 7 day period of psychosocial stress before being treated daily with SLV-323 (20 mg kg(-1) day(-1)). The psychosocial stress continued throughout the treatment period of 28 days. Brain metabolite concentrations were determined in vivo by proton magnetic resonance spectroscopy. Norepinephrine excretion was monitored from daily urine samples, and serum testosterone concentrations were measured at the end of the experiment. All animals were videotaped daily to analyze scent-marking behavior and locomotor activity. Cell proliferation in the dentate gyrus and hippocampal volume were measured postmortem. RESULTS: Stress significantly decreased cerebral concentrations of N-acetyl-aspartate, total creatine, and choline-containing compounds in vivo and resulted in an increase of urinary norepinephrine and decrease of serum testosterone concentrations. Moreover, stressed animals displayed decreased scent-marking behavior and locomotor activity. The proliferation rate of the granule precursor cells in the dentate gyrus was reduced, and hippocampal volume was mildly decreased. The stress-induced alterations in the central nervous system were partially prevented by concomitant administration of SLV-323, while drug treatment had only a minor effect on the stress-induced behavioral changes. CONCLUSIONS: The novel NK1R antagonist SLV-323 has certain antidepressant-like effects in a valid animal model of depression.

Animals↗

PubMed2005

Chronic stress decreases the number of parvalbumin-immunoreactive interneurons in the hippocampus: prevention by treatment with a substance P receptor (NK1) antagonist.

Previous studies have demonstrated that stress may affect the hippocampal GABAergic system. Here, we examined whether long-term psychosocial stress influenced the number of parvalbumin-containing GABAergic cells, known to provide the most powerful inhibitory input to the perisomatic region of principal cells. Adult male tree shrews were submitted to 5 weeks of stress, after which immunocytochemical and quantitative stereological techniques were used to estimate the total number of hippocampal parvalbumin-immunoreactive (PV-IR) neurons. Stress significantly decreased the number of PV-IR cells in the dentate gyrus (DG) (-33%), CA2 (-28%), and CA3 (-29%), whereas the CA1 was not affected. Additionally, we examined whether antidepressant treatment offered protection from this stress-induced effect. We administered fluoxetine (15 mg/kg per day) and SLV-323 (20 mg/kg per day), a novel neurokinin 1 receptor (NK1R) antagonist, because the NK1R has been proposed as a possible target for novel antidepressant therapies. Animals were subjected to a 7-day period of psychosocial stress before the onset of daily oral administration of the drugs, with stress continued throughout the 28-day treatment period. NK1R antagonist administration completely prevented the stress-induced reduction of the number of PV-IR interneurons, whereas fluoxetine attenuated this decrement in the DG, without affecting the CA2 and CA3. The effect of stress on interneuron numbers may reflect real cell loss; alternatively, parvalbumin concentration is diminished in the neurons, which might indicate a compensatory attempt. In either case, antidepressant treatment offered protection from the effect of stress and appears to modulate the hippocampal GABAergic system. Furthermore, the NK1R antagonist SLV-323 showed neurobiological efficacy similar to that of fluoxetine.

Animals↗

PubMed2005

[Neuroplasticity and depression].

Early hypotheses on the pathophysiology of mood disorders were based on aberrant intrasynaptic concentrations of the neurotransmitters serotonin and norepinephrine. However, recent neuroimaging and post mortem morphometric studies demonstrated selective structural and morphological (macroscopic and microscopic) changes across various limbic and non-limbic circuits in the brains of depressed patients. Recently, these two types of observations seem to converge at the cellular and molecular level. It has been revealed, that stress and antidepressant treatment have an opposite effect on the intracellular signaling, transcription factors and target genes. In some cases, the factors that are influenced by antidepressants (e.g. cAMP-CREB cascade, BDNF) have also been identified as important mediators of learning and memory. An evolving new hypothesis in the pathophysiology and treatment of depression involves adaptation or plasticity of neural systems. Depression could result from an inability to make the appropriate adaptive responses to stress or aversive stimuli. It is possible that antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of neurons and by increasing cell survival and function.

Antidepressive Agents↗

PubMed2004

[The connection between mentalization deficit and pragmatic language skills and neurocognition in schizophrenia].

OBJECTIVE: There is an increasing interest in the background of mentalization deficit in schizophrenia. On the one hand, according to developmental psychological studies, mentalization development is connected with the development of pragmatic language skills. On the other hand, studies suggest that mentalization is dependent on the maturation of neurocognitive skills such as executive functions. Our study investigated the role of these domains in the mentalization deficit of schizophrenia. METHOD: 28 patients with schizophrenia and 20 control patients with depression took part in the first part of the study. Participants were presented first-order and second-order mentalization tasks, metaphor and irony tasks for the assessment of mentalizing skills. The pragmatic language skills were examined by "question and answer" vignettes. 20 patients with schizophrenia took part in the second part of the study. The test battery was completed with a picture recognition task and neurocognitive tests were made by all patients. RESULTS: Patients with schizophrenia performed significantly worse in the irony and pragmatic tasks, but there was no correlation between their performances in the irony and in the pragmatic tasks. Selective attention and verbal working memory showed correlation with the cumulative verbal mentalization index. Selective attention correlated with the recognition of complex mental states from pictures as well, but the successful decoding of complex mental states was dependent on the recognition of basic expressions. Attention correlated with mental state recognition as well. CONCLUSIONS: Our results suggest that the mentalization deficits of people with schizophrenia cannot be explained by pragmatic language deficits alone, and the manifest impairment is the consequence of disturbances in multiple cognitive processes. Basic neurocognitive factors such as attention, selective attention and verbal working memory can influence the mentalization skills.

Case-Control Studies↗

PubMedDate not supplied

'Clonal pluralization of the self': a new form of delusional misidentification syndrome.

The authors present a patient with paranoid schizophrenia, who has the delusion that he exists in plural numbers. The patient declares these doubles to be both psychologically and physically completely identical to him, and he believes 'them' to be in fact women. In connection with the case, the authors discuss the phenomena of reduplicative paramnesia and clonal pluralization, and they suggest introducing the psychopathological term 'clonal pluralization of the self' for the reported phenomenon.

Adult↗