Marek Krzystanek

Nesfatin-1, a unique regulatory neuropeptide of the brain

Nesfatin-1, a newly discovered NUCB2-derived satiety neuropeptide is expressed in several neurons of forebrain, hindbrain, brainstem and spinal cord. This novel anorexigenic substance seems to play an important role in hypothalamic pathways regulating food intake and energy homeostasis. Nesfatin-1 immunoreactive cells are detectable in arcuate (ARC), paraventricular (PVN) and supraoptic nuclei (SON), where the peptide is colocalized with POMC/CART, NPY, oxytocin and vasopressin. The nesfatin-1 molecule interacts with a G-protein coupled receptor and its cytophysiological effect depends on inhibitory hyperpolarization of NPY/AgRP neurons in ARC and melanocortin signaling in PVN. Administration of nesfatin-1 significantly inhibits consumatory behavior and decreases weight gain in experimental animals. These recent findings suggest the evidence for nesfatin-1 involvement in other important brain functions such as reproduction, sleep, cognition and anxiety- or stress-related responses. The neuroprotective and antiapoptotic properties of nesfatin-1 were also reported. From the clinical viewpoint it should be noteworthy, that the serum concentration of nesfatin-1 may be a sensitive marker of epileptic seizures. However, the details of nesfatin-1 physiology ought to be clarified, and it may be considered suitable in the future, as a potential drug in the pharmacotherapy of obesity, especially in patients treated with antipsychotics and antidepressants. On the other hand, some putative nesfatin-1 antagonists may improve eating disorders.

Platelet phospholipase A2 activity in patients with Alzheimer’s disease, vascular dementia and ischemic stroke

SummaryPhospholipase A2 (E.C. 3.1.1.4, PLA2) plays an essential role in metabolism of membrane phospholipids, it is related to inflammatory reactions, secretion of amyloid precursor protein and activation of NMDA receptor after ischemia.In the present study we investigated PLA2 activity in platelets from 37 Alzheimer’s disease (AD) patients, 32 vascular dementia (VaD) patients and 32 individuals with ischemic stroke as compared to 27 healthy elderly controls. PLA2 activity was determined using radiometric assay.Mean platelet PLA2 activity was increased in individuals with Alzheimer’s disease (p < 0.001). In VaD group the enzyme activity was between the values in AD and controls, these differences being significant from both groups. In the group of patients with ischemic stroke mean PLA2 activity was higher either 48 h after the stroke or 7 days later (in both cases p < 0.001).The results may be particularly interesting in light of the fact, that inhibitors of PLA2 activity are known.

Bright light therapy in the treatment of childhood and adolescence depression, antepartum depression, and eating disorders

Circadian rhythm disorders represent an important component underlying the pathology of depression. One of the subtypes of depression, in which these disorders may play a crucial role, is the seasonal affective disorder (SAD). The bright light therapy (BLT) has been reported as a novel, promising treatment method for SAD since 1984, and most of the data revealing its efficacy has been referred to adult patients, without comorbid disorders. However, in the recent years, more and more reports have been presented, which confirm the usefulness of BLT in some specific subpopulations of patients, including children, adolescents and pregnant women. The present review summarizes the applications of BLT in antepartum depression, childhood and adolescence depression as well as in patients suffering from eating disorders. Although the body of evidence is still too small to recommend the use of BLT as the first line of treatment for the depression or eating disorders in these patient subpopulations; it appears that BLT may be a useful alternative or adjunctive therapy for these diseases. However, the specific clinical applications of BLT in these areas need further investigation.

Bright light treatment of depressive symptoms in patients with restrictive type of anorexia nervosa.

BACKGROUND Light therapy refers to two different categories of treatment. One of them is used in common medical practice and the other in complementary medicine. The aim of the study was to assess the effect of short time (6 weeks) bright light treatment (BLT) on depressive symptoms in female patients with the restrictive type of anorexia nervosa (AN-R). METHODS Twenty-four girls, aged 15-20 (mean 17.4±1) years, diagnosed as AN-R, with concomitant depressive symptoms ≥17 points on the 21-item Hamilton Depression Rating Scale (HDRS) were studied. All girls received cognitive behavioral therapy. Among them, twelve were randomly assigned to additional treatment with BLT for 6 weeks (10,000 lux, 30 min daily). Both groups did not differ on baseline demographic and clinical parameters. The assessments of depression by means of HDRS and measuring of body mass index (BMI) were done weekly throughout the treatment. RESULTS Improvement of depression was significantly greater in the group receiving BLT, with a significant difference between groups in depression intensity after 5 and 6 weeks. There was no difference in the increase of BMI between groups after 6 weeks, although such increase started earlier in patients treated with BLT. LIMITATIONS Six weeks of treatment may be an insufficient duration to draw the conclusion about the efficacy of BLT and a follow-up is needed to assess the maintenance of the effect. CONCLUSIONS The results obtained may suggest that BLT could be an effective non-pharmacological modality for the treatment of depression in patients with AN-R.

Effects of long-term treatment with the neuroleptics haloperidol, clozapine and olanzapine on immunoexpression of NMDA receptor subunits NR1, NR2A and NR2B in the rat hippocampus.

BACKGROUND Antagonists of the N-methyl-d-aspartate receptor (NMDA-R) are associated with symptoms of schizophrenia, leading to the hypothesis that NMDA-R hypofunction leads to the pathogenesis of disease. We evaluated the long-term effect of neuroleptic administration on the NMDA subunits via immunohistochemical analysis. METHODS Rats received olanzapine, clozapine and haloperidol before evaluation of the expression of the NR1, NR2A and NR2B subunit proteins in the hippocampal areas of the brain, via a densytometric analysis of immunoexpression in the rat hippocampus. RESULTS All of the neuroleptics examined caused a decrease in the expression of the NR1 subunit, and thus, one can assume that both olanzapine, clozapine and haloperidol decreased the number of NMDA receptors in the CA1 and CA2 areas of the brain. CONCLUSIONS A decrease in hippocampal glutamatergic signalling after long-term neuroleptic administration may cautiously explain the incomplete effectiveness of these drugs in the therapy of schizophrenia-related cognitive disturbances.

Sleep and inflammatory markers in different psychiatric disorders

Many psychiatric disorders, like schizophrenia, affective disorders, addictions and different forms of dementia are associated with sleep disturbances. In the etiology and course of those diseases inflammatory processes are regarded to be an increasingly important factor. They are also a frequently discussed element of the pathology of sleep. In this literature review reports on correlations between poor sleep and inflammatory responses in various psychiatric conditions are discussed. The link between schizophrenia, affective disorders and inflammatory cytokines is a complex phenomenon, which has been already confirmed in a number of studies. However, the presence of sleep deficits in those conditions, being a common symptom of depression and psychoses, can be an additional factor having a considerable impact on the immunological processes in mental illnesses. In the analyzed data, a number of studies are presented describing the role of inflammatory markers in sleep disturbances and psychopathological symptoms of affective, psychotic, neurogenerative and other disorders. Also attention is drawn to possible implications for their treatment. Efforts to use, e.g., anti-inflammatory agents in psychiatry in the context of their impact on sleep are reported. The aspect of inflammatory markers in the role of sleep deprivation as the treatment method in major depressive disorder is also discussed. A general conclusion is drawn that the improvement of sleep quality plays a crucial role in the care for psychiatric patients.

Impact of pharmacological and psychological treatment methods of depressive and anxiety disorders on cognitive functioning.

Anxiety and depressive disorders are characterized by a number of clinical symptoms like decreased mood, apathy, anhedonia and anxiety. An important element of the clinical picture is also neurocognitive impairment. The most common treatment methods for depression and anxiety are pharmacology, psychotherapy or a combination of both methods. The data from literature show that those treatment methods lead to an improvement of clinical symptoms, but they exert a possible impact on cognitive functions. However the study results referring both to the role of pharmacological treatment and psychotherapy in this domain are still inconsistent. There is an increasing number of accessible data confirming the positive effects of those clinical interventions on cognitive functioning of anxiety and depressive patients, but the interpretation is complicated because of differences in methodology as well as examined sample size and their characteristics. More studies are then needed to describe this phenomenon.

Escitalopram affects spexin expression in the rat hypothalamus, hippocampus and striatum

BACKGROUND Spexin (SPX) is a recently discovered neuropeptide that exhibits a large spectrum of central and peripheral regulatory activity, especially when considered as a potent anorexigenic factor. It has already been proven that antidepressants, including selective serotonin reuptake inhibitors (SSRI), can modulate peptidergic signaling in various brain structures. Despite these findings, there is so far no information regarding the influence of treatment with the SSRI antidepressant escitalopram on brain SPX expression. METHODS In this current study we measured SPX mRNA and protein expression in the selected brain structures (hypothalamus, hippocampus and striatum) of rats chronically treated with a 10mg/kg dose of escitalopram using quantitative Real-Time PCR and immunohistochemistry. RESULTS Strikingly, long-term (4 week) drug treatment led to the downregulation of SPX expression in the rat hypothalamus. This supports the hypothesis that SPX may be involved in the hypothalamic serotonin-dependent actions of SSRI antidepressants and possibly also in the central mechanism of body mass increase. Conversely, SPX expression increased in the hippocampus and striatum. CONCLUSIONS This is the first report of the effects of a neuropsychiatric medication on SPX expression in animal brain. Our findings shed a new light on the pharmacology of antidepressants and may contribute to a better understanding of the alternative mechanisms responsible for antidepressant action.

Extended neuroleptic administration modulates NMDA-R subunit immunoexpression in the rat neocortex and diencephalon

BACKGROUND This study aimed to evaluate the effect of extended olanzapine, clozapine and haloperidol administration on NMDA-R subunit immunoexpression in the rat neocortex and diencephalon. METHODS To explore NR1, NR2A and NR2B subunit protein expression, densytometric analysis of immunohistochemically stained brain slices was performed. RESULTS Interestingly, all neuroleptics caused a downregulation of NMDA-R subunit expression in the thalamus but increased the level of NR1 in the hypothalamus. Olanzapine upregulated hypothalamic NR2A expression, while clozapine and haloperidol decreased hypothalamic levels. We observed no significant changes in NR2B immunoreactivity. None of the studied medications had significant influence on NMDA-R subunit expression in the neocortex. CONCLUSIONS Neuroleptic-induced reduction in the expression of thalamic NMDA-R subunits may play an important role in the regulation of glutamatergic transmission disorders in cortico-striato-thalamo-cortical loop in schizophrenia. A decrease in NMDA signaling in this region after long-term neuroleptic administration may also cautiously explain the incomplete effectiveness of these drugs in the therapy of schizophrenia-related cognitive disturbances.

An open, large, 6-month naturalistic study of outcome in schizophrenic outpatients, treated with olanzapine

In many countries of the industrialised world second generation (“atypical”) antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics.