Long-term treatment with haloperidol affects neuropeptide S and NPSR mRNA levels in the rat brain

OBJECTIVE: The brainstem-derived neuropeptide S (NPS) has a multidirectional regulatory activity, especially as a potent anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signalling in various brain structures. However, there is no information regarding the influence of haloperidol on NPS and NPS receptor (NPSR) expression. METHODS: We assessed NPS and NPSR mRNA levels in brains of rats treated with haloperidol using quantitative real-time polymerase chain reaction. RESULTS: Chronic haloperidol treatment (4 weeks) led to a striking upregulation of NPS and NPSR expression in the rat brainstem. Conversely, the NPSR mRNA expression was decreased in the hippocampus and striatum. CONCLUSIONS: This stark increase of NPS in response to haloperidol treatment supports the hypothesis that this neuropeptide is involved in the dopamine-dependent anxiolytic actions of neuroleptics and possibly also in the pathophysiology of mental disorders. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications

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. (C) 2011 Elsevier Ltd. All rights reserved

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

The comparison of multipotential for differentiation of progenitor mesenchymal-like stem cells obtained from livers of young and old rats.

The presence of stem cells differentiating to hepatocytes and cholangiocytes has been previously reported in livers of young rats. Here, we have isolated, cultured, and characterized mesenchymal stem cells (MSCs) from livers of young and old rats and tested their multipotential for differentiation. The mesenchymal stem cells in liver sections were identified by the presence of markers, respectively for primary stem cells Thy-1 and CD34, for differentiation to early cholangiocytes GST and CK19, and for differentiation to hepatocytes GSTalpha and CK18. Ki67 was detected as the cell proliferation marker. Cells isolated from livers of either age group were tested in a culture for their viability following storage and were characterized for the presence of most of the markers detected in cells in situ. The results revealed age-dependent changes in the number of recovered primary MSCs. In both age groups we have observed cells changing under differentiating conditions to liver cell lineages, such as cholangiocytes and hepatocytes, as well as to non-liver cells such as adipocytes, astrocytes, neuroblasts, and osteoblasts. Our data revealed that from the livers of rats 20 months and older the primary MSCs could be isolated and expanded; however, they were significantly fewer, even though their differentiation multipotential was preserved. The mechanism involved in the differentiation of liver MSCs seemed to depend on a constellation of signals in Notch signalling pathways. Thus, our results support the idea of potential use of liver as a source of MSCs, not only for liver reconstruction but also for cell therapy in general

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 10 mg/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

Long-term treatment with olanzapine increases the number of Sox2 and doublecortin expressing cells in the adult subventricular zone

Continuously active neurogenic regions in the adult brain are located in the subventricular zone (SVZ) of the lateral ventricles and subgranular zone (SGZ) of the hippocampal dentate gyrus. Neurogenesis is modulated by many factors such as growth factors, neurotransmitters and hormones. Neuropsychiatric drugs, especially antidepressants, mood stabilizers and antipsychotics may also affect the origin of neuronal cells. The purpose of this study was to determine the effects of chronic olanzapine treatment on adult rat neurogenesis at the level of the SVZ. The number of neuroblasts was evaluated using immunohistochemical and fluorescent detection of sex determining region Y-box 2 (Sox-2) and doublecortin (DCX) expressing cells. The results indicate that olanzapine has proneurogenic effects in the adult rat SVZ, as the mean number of sex determining region Y-box 2 (Sox-2) and doublecortin-positive cells increased significantly, while there was a similar tendency in the subgranular zone SGZ. Collectively, these results suggest that long-term treatment with olanzapine may stimulate neurogenic stem cell formation in the SVZ which supports adult neurogenesis

Post-tracheostomy complications: respiratory failure caused by authologic foreign body – case report

Tracheostomy is performed frequently as a palliative treatment in patients with end-stage respiratory failure (RF). However, in patients requiring prolonged mechanical ventilation it may be difficult to recognize and can often lead to life-threatening RF. We present two cases of acute-on-chronic respiratory failure (ACRF) occurring in patients who had undergone tracheostomy [one with percutaneous dilatational tracheostomy (PDT) and the second with surgical tracheostomy (ST)]. The first case was admitted due to ACRF several months after previous successful decannulation and the second case after failure of several attempts of weaning from tracheal cannula. In both cases, noninvasive mechanical ventilation assisted flexible bronchoscopy (NIV-FB) was able to identify and solve the tracheal stenosis secondary to stiff bananashaped whitish foreign bodies. Histology sampling and genetic testing confirmed autologous foreign body formation—tracheal cartilage calcification. NIV-FB was found to be safe and effective in both diagnosis and treatment of the tracheal stenosis. Life-threatening RF connected with tracheal stenosis may be caused by rupture of tracheal cartilage ossification in patients with a history of ST and PDT. Bronchofiberoscopy performed with NIV will be a useful procedure to evaluate and treat the respiratory tract in patients with RF with suspected tracheal stenosis