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1

Stress-induced changes in gene expression of catecholamine enzymes and adrenoceptors in heart of sham-operated and PVN-deafferentated rats

100%
Bohacova V., Mravec B., Laukova M., Kvetnansky R.
Acta Neurobiologiae Experimentalis
|
2009
|
tom 69
|
nr 3
The paraventricular nucleus of the hypothalamus (PVN) regulates neuroendocrine, autonomic and cardiovascular responses to stress. Stressors activate catacholaminergic systems which consequently modulates activity of organism via adrenergic receptors (ARs). Our work was focused on investigation of changes in gene expression of epinephrine-synthesizing enzyme phenylethanolamine-N-methyltransferase (PNMT), neuropeptide Y (NPY) and adrenoceptors in the heart of sham-operated and PVN-deafferentated rats exposed to immobilization stress (IMO). PNMT and NPY mRNA levels in the heart of sham-operated rats were not signifi cantly increased after a single IMO. However, posterolateral deafferentation of the PVN reduced PNMT mRNA, whereas levels of NPY mRNA were elevated. These data suggest a stimulatory role of PVN on PNMT and an inhibitory role on NPY gene expression. Moreover, β1-AR mRNA levels were signifi cantly reduced in heart of PVN-deafferentated animals comparing to sham-operated rats. On other side, after single IMO β1-AR mRNA levels were signifi cantly increased in PVN-deafferentated rats. Gene expression of other ARs (β2, β3, α1B) in hearts of stressed PVN-deafferentated animals were decreased. The found down-regulation of gene expression of ARs might suggest a rise in sympathetic activity induced by PVN deafferentation. Our data suggest that PVN plays an important role in stress-induced activation of cardiac sympathetic system.
2

Brain response to peripheral tumors in rats-the study of neurobiology of cancer

76%
Mravec B., Lackovicova L., Bundzikova J., Bizik J., Hulin L., Kiss A.
Acta Neurobiologiae Experimentalis
|
2009
|
tom 69
|
nr 3
A signifi cant amount of data has emerged supporting the hypothesis that the central nervous system might monitor and modulate tumor growth. The aim of our study was to investigate whether intraperitoneal tumor growth may induce detectable changes in brain structures that are involved in the response to immune challenges. Using Fos immunohistochemistry we investigated the effect of a tumor induced by a single intraperitoneal injection of BP6-TU2 fi brosarcoma cells to male Wistar rats on the activity of selected brain structures. Twenty eight days after the tumor cells administration we found an increased Fos expression in the nucleus tractus solitarii/A2, A1 noradrenergic cells, parabrachial nucleus as well as in the hypothalamic paraventricular, supraoptic and accessory neurons. These structures are involved in the processing of signals related to immune challenges and consequent elaboration of neuro-endocrine responses. Obtained data supports the view that the signals related to peripheral tumor development might be transmitted to the brain. Further studies are necessary to reveal whether our fi ndings can be attributed to a specifi c effect of cancer or whether observed changes in the activity of neuronal structures refl ex processes that only accompany the cancer progression.
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Response of hypothalamic oxytocinergic neurons to immobilization stress is not dependent on the presence of corticotrophin releasing hormone (CRH): a CRH knock-out mouse study

76%
Pirnik Z., Petrak J., Bundzikova J., Mravec B., Kvetnansky R., Kiss A.
Journal of Physiology and Pharmacology
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2009
|
tom 60
|
nr 2
77-82
This study explores the quantitative patterns of immunolabeled Fos protein incidence in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) oxytocinergic (OXY) neurons in response to immobilization (IMO) stress in corticotrophin releasing hormone deficient (CRH-KO) mice. Adult male mice, taken directly from cages or 120 min after a single IMO, were sacrificed by intracardial perfusion with fixative. Coronal brain sections of 30 µm thickness were processed for dual Fos/OXY immunohistochemistry. In control wild type (WT) and CRH-KO mice, scattered Fos immunoreactivity was observed in hypothalamus, including the PVN where scanty Fos signal occurred in both parvocellular and magnocellular PVN subdivisions. Dual Fos/OXY immunostainings revealed higher basal Fos expression in the PVN of control CRH-KO mice. IMO evoked a marked rise in Fos expression in OXY neurons of the PVN and SON in both WT and CRH-KO groups of mice. The present data demonstrate that 1/ CRH deficiency upregulates the basal activity of hypothalamic PVN OXY cells in CRH-KO mice and 2/ IMO stress in both WT and CRH-KO mice affects distinctly the activity of OXY cells in both SON and PVN. Our data indicate that CRH deficiency does not alter the responsiveness of PVN and SON OXY cells to IMO stress.
4

The effect of the autonomic nervous system on the survival of rats implanted with yoshida ascites tumor cells

64%
Ondicova K., Lackovicova L., Valaskova Z., Macikova L., Perzelova A., Hulin L., Gidron Y., Mravec B.
Acta Neurobiologiae Experimentalis
|
2009
|
tom 69
|
nr 3
Even if it is suggested that stress does not directly induce cancer there is plenty of evidence that shows that stress represents an important factor facilitating cancer progression, however the exact mechanisms and pathways are not known in details. Because the autonomic nervous system plays an important role in the elaboration of stress response, we investigated the effect of the disruption of the sympathetic or parasympathetic system on the survival of tumor bearing rats. We used male Wistar rats in which we performed either chemical sympathectomy induced by intraperitoneal application of 6-OH dopamine or subdiaphragmatic vagotomy by surgical dissection of the vagus nerve. After a regeneration period we administered intraperitoneally to sympathectomized, vagotomized and sham operated rats Yoshida ascites cells. We have found that whereas chemical sympathectomy signifi cantly reduced the survival of tumor bearing rats, subdiaphragmatic vagotomy had only a slight effect on reducing the survival of rats implanted by Yoshida cells. Our fi ndings suggest that the autonomic nervous system, especially its sympathetic division, plays an important role in the regulation of the development of Yoshida ascites tumor cells in rats. We suggest that whereas long lasting sympathetic activation as a consequence of exposure to chronic stress might have a promoting effect on cancer growth, the sympathetic system might have, during basal conditions, a modulatory effect on tumor progression.
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