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Journal Article 2013; 34(1): 58-61 PubMed PMID: 23524625 Citation  Keywords:  Animals, Cholinergic Neurons:drug effects, Cholinesterase Inhibitors:pharmacology, Heart Rate:drug effects, Hippocampus:cytology, Hypothalamo-Hypophyseal System:cytology, Male, Microinjections, Neostigmine:pharmacology, Pituitary-Adrenal System:cytology, .   

OBJECTIVES: We previously demonstrated that the direct microinjection of cholinesterase inhibitor (neostigmine) into the hippocampus in rats activated the hypothalamo-pituitary -adrenal axis and increased the level of norepinephrine in the plasma. In the current study we tried to measure the effects of neostigmine injection into the hippocampus using the non-invasive measure of heart rate variability (HRV).

MATERIALS AND METHODS: After the hippocampal injection of neostigmine (50 nM and 125 nM) or saline as a control in rats, HRV measurement was performed for 30 min.

RESULTS: After the injection of neostigmine into the hippocampus, LF/HF, the index of the sympathetic nervous system, significantly increased.

CONCLUSIONS: The results of the current study indicated that stimulation of the hippocampal cholinergic system induced the activation of the sympathetic nervous system....

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Journal Article 2012; 33(7): 703-708 PubMed PMID: 23391881 Citation  Keywords:  Animals, Antithyroid Agents:pharmacology, Body Temperature:drug effects, Body Weight:drug effects, Brain Chemistry:drug effects, Eating:drug effects, Energy Metabolism:drug effects, Hypothalamus:drug effects, Hypothyroidism:chemically induced, Male, Methi.   

OBJECTIVES: We evaluated the contribution of the thyroid hormones to the long-term maintenance of feeding behavior and body weight, while distinguishing their direct central effects from those resulting from the metabolic rate in the peripheral tissues.

METHODS: We assessed the effect of hypothyroidism on the long-term (6 months) regulation of food intake, body weight, and energy expenditure in rats. We then generated the recovery of a euthyroid condition in the brain while maintaining a low T3 availability for the peripheral organs, i.e. a combined condition of central euthyroidism with peripheral hypothyroidism, with the aid of a pharmacological combination.

RESULTS: Hypothyroidism caused a decrease in the daily food intake, body weight, and body temperature. The food intake and body temperature stabilized at a lower value, whereas body weight kept decreasing at a constant rate. The administration of exogenous T4 increased food intake and body-weight gain, but had no effect on body temperature.

CONCLUSIONS: The thyroid hormones are necessary for the long-term regulation of energy intake, storage, and expenditure by different mechanisms. The feeding behavior seems to be partially dependent on a direct action of the thyroid hormones on the brain and this effect is independent of the energy expenditure in the peripheral organs. The body weight is closely dependent on the thyroid status and its maintenance seems to involve thyroid action on mechanisms other than feeding and metabolic rate....

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Case Reports 2012; 33(6): 590-596 PubMed PMID: 23160226 Citation  Keywords:  Aged, Brain Neoplasms:diagnosis, Fatal Outcome, Female, Humans, Hydrocephalus:diagnosis, Hypothalamic Diseases:diagnosis, Hypothalamus:surgery, Male, Middle Aged, Neurosurgical Procedures:adverse effects, Postoperative Complications:diagnosis, Subdural Ef.   

BACKGROUND: Opening of the lamina terminalis is often used in surgery of the optico-chiasmatic region. Consequently, alteration of cerebral-spinal fluid (CSF) dynamics can occur after this manoeuvre, thus potentially translating into clinical complications. Herein, we describe 2 cases in which clinically relevant hypothalamic dysfunctions developed after few days opening of the lamina terminalis both patients showed mild to moderate preoperative hydrocephalus which improved postoperatively.

CASES DESCRIPTION: In a patient with ruptured aneurysm of the basilar bifurcation, opening of the lamina terminalis was performed prior to acute-stage clipping. On postoperative day 7th, the patient developed significant subdural hygroma, mild disturbances of consciousness and increase of ADH concentration. These clinical features resolved only following subdural hygroma drainage and ventricular-peritoneal shunting. One previously operated patient in whom the lamina terminalis had been opened to remove a sizeable parasellar tumour showed a similar post-operative course. In this patient, sole subdural hygroma drainage was not an effective treatment, and the patient died subsequently for complications related to long-standing, though mild, hypothalamic dysfunction.

CONCLUSIONS: Our experience may suggest that hypothalamic dysfunctions should be reminded as a possible, although rare, complication following the opening of the lamina terminalis. This clinical condition, if not properly managed, may contribute to trigger severe life-threatening complications....

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Journal Article 2012; 33(4): 393-400 PubMed PMID: 22936265 Citation  Keywords:  Animals, Cattle, Cerebellar Nuclei:cytology, Female, Glutamic Acid:metabolism, Hypothalamus:physiology, Immunity, Humoral:physiology, Male, Neuroimmunomodulation:physiology, Neurons:immunology, Rats, Rats, Sprague-Dawley, Serum Albumin, Bovine:immunology,.   

OBJECTIVES: We explored effect of glutamatergic neurons in the fastigial nucleus (FN), one of three cerebellar nuclei, on humoral immunity and revealed that this effect was mediated by the hypothalamus via FN-hypothalamic glutamatergic transmission.

METHODS: Rats were immunized with bovine serum albumin (BSA). On the third day after the immunization, 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of glutaminase for glutamate synthesis, was microinjected in bilateral FN and D,L-threo-β-hydroxyaspartic acid (THA), an inhibitor of glutamate transporters on plasma membrane, was microinjected in both sides of lateral hypothalamic area (LHA). Glutamate content in the hypothalamus was examined by high-performance liquid chromatography (HPLC). Flow cytometry and enzyme-linked immunosorbent assay (ELISA) were used to measure B lymphocyte percentage in mononuclear cells of peripheral blood and levels of anti-BSA IgM and IgG antibodies in the serum, respectively.

RESULTS: DON injection in bilateral FN reduced B lymphocyte percentage and anti-BSA IgM and IgG levels, and simultaneously decreased glutamate content in the hypothalamus. Combined treatment with DON in the FN and with THA in the LHA elevated B cell number and anti-BSA IgM and IgG levels and increased hypothalamic glutamate content compared with DON treatment alone. However, combined treatment with DON in the FN and with THA in the ventrolateral thalamic nuclei (VL) did not significantly alter DON-dependent changes in B cell number and antibody levels, although the co-treatment altered DON-dependent glutamate content in the thalamus.

CONCLUSION: Cerebellar FN glutamatergic neurons participate in modulation of humoral immunity and this effect is mediated by the hypothalamus via FN-hypothalamic glutamatergic transmission....

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Journal Article 2012; 33(2): 138-148 PubMed PMID: 22592194 Citation  Keywords:  Animals, Body Weight:drug effects, Estradiol:blood, Female, Follicle Stimulating Hormone:blood, Gonadotrophs:drug effects, Gonadotropin-Releasing Hormone:blood, Growth Hormone:blood, Hypothalamus:drug effects, Insulin-Like Growth Factor I:metabolism, Lept.   

OBJECTIVE: Available data suggest that estrogens and leptin play a role in the control of the pubertal process. In humans and some mammal species the increase of the activity of gonadotropic axis accompanies the decrease in the rate of growth at puberty. The effect of 17β-estradiol and/or leptin administration on the somatotropic and gonadotropic axes was studied using prepubertal female rats as an animal model.

MATERIAL AND METHODS: Prepubertal female rats received estradiol/saline, estradiol/leptin, oil/leptin or oil/saline (vehicles) respectively. The changes of growth rate, and serum 17β-estradiol, leptin, GH, IGF-I and gonadotropins levels as well as LHRH and estrogen receptor (ER) concentrations in the medial basal hypothalamus (MBH) and the pituitary were determined. All hormones concentrations were measured by radioimmunoassay and ER by radioligand methods .

RESULTS: In estradiol and/or leptin treated animals noticeable reduction of rate of growth was found. The decrease of growth in response to estradiol treatment accompanied the increase GH level and the decrease of IGF-I concentration in the circulation. Both hormones operating together activated reproductive axis, what was manifested by a significant increase of LHRH abundant in the hypothalamus as well as elevated LH and FSH levels in the circulation. In these rats a significant decrease of the estrogen receptor concentrations in the pituitary was observed.

CONCLUSION: The role of estradiol and leptin in the control of growth and reproduction seems to overlap only partially. Estradiol plays a significant role in the activation of the reproductive axis, and leptin takes part as a permissive factor in pubertal process....

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Journal Article 2012; 33(2): 124-132 PubMed PMID: 22592192 Citation  Keywords:  Animals, Gene Expression:physiology, Hypothalamo-Hypophyseal System:physiology, Male, Myocardium:cytology, Pituitary-Adrenal System:physiology, Protein Transport, Rats, Rats, Inbred Lew, Rats, Sprague-Dawley, Rats, Wistar, Receptors, Oxytocin:biosynthesis.   

OBJECTIVES: Cardiovascular system is regulated by a diverse array of hormones, neurotransmitters and neuropeptides. Oxytocin and its receptors (OTR) were also shown to regulate cardiovascular functions and this hormone was even called cardiovascular hormone. In recent publication, we demonstrated the expression of mRNA of OTR by real-time quantitative PCR (RT qPCR) in all rat heart compartments. The aim of this study was to investigate the effects of acute restraint stress on OTR mRNA expression in two rat strains with different activity of HPA axis.

METHODS: Adult male Sprague-Dawley and Lewis rats, the latter strain reported to have lower HPA activity, were used in RT qPCR studies and Wistar rats in immunofluorescent ones. Both acute restraint (IS) and this stress combined with the immersion of rats in water (ICS) lasted 60 min. Gene expression of OTR mRNA was estimated in all heart compartments after 1 or 3 hours after stress termination (IS1, IS3, ICS1, ICS3). The relative expression was calculated using 2(-ΔΔC)T method. In immunofluorescent studies we used commercial specific OTR antibodies.

RESULTS: In RT qPCR studies we found higher expression of OTR mRNA in atria than in ventricles and no statistical differences between Sprague-Dawley and Lewis rats under basal conditions. Relative expression of OTR mRNA after 60 min lasting stress exposure differed in dependence on the stress type and partly on the time interval after the stress termination. When compared to controls, in rat left atria both stressors caused inhibition of OTR mRNA expression in both rat strains. In rat ventricles, which have very low OTR mRNA expression, there was a significant difference in the effect of two stressors. In most groups ICS displayed the increase of OTR mRNA expression if compared to IS groups. Immunofluorescent studies revealed changes induced by acute restraint stress in all heart compartments. The immunofluorescent studies suggested that acute stress induces higher colocalization of OTR with the nuclei than it was observed in the controls.

CONCLUSIONS: The expression of OTR mRNA in all heart compartments of controls as well as after stress exposure in Sprague-Dawley and Lewis rats support the notion that OTR plays a regulatory role in the cardiovascular system and is also involved in the regulations in the heart after stress. The immunofluorescent observation that OTRs coexpress in areas of cell nuclei in certain heart compartments and after acute stress, compared to controls, requires further studies....

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Journal Article 2011; 32(6): 805-810 PubMed PMID: 22286791 Citation  Keywords:  Animals, Hypothalamo-Hypophyseal System:physiology, Male, Myocardium:cytology, Oxytocin:metabolism, Pituitary-Adrenal System:physiology, RNA, Messenger:metabolism, Rats, Rats, Inbred Lew, Rats, Sprague-Dawley, Receptors, Oxytocin:genetics,.   

OBJECTIVES: Oxytocin (OT) is a neuropeptide acting both as a peripheral hormone and in the brain as neurotransmitter and neuromodulator. In addition to its well-known effects on milk-ejection and uterine contraction, OT was shown to exert neuroendocrine regulation of heart functions. The aim of this study was to investigate the expression of mRNA of OT receptors (OTR) in rat hearts by real-time quantitative PCR (qPCR). The study was performed in Sprague-Dawley (SD) and Lewis (LE) rat strains, the latter having lower activity of HPA axis.

METHODS: We used adult male SD and LE rats. OTR mRNA expression was detected in all heart chambers by comparing their threshold cycle values (CT) to CT of reference gene β-actin. The relative expression ratios were calculated using the 2-ΔΔCT method. The specificity of reaction of primary antibody with OTRs was tested by Western Blot and localization of OTR in the heart compartments was performed by immunofluorescence with commercial OTR specific antibodies.

RESULTS: We found expression of OTR mRNA in all heart compartments. The expression of OTR mRNA in both atria (LA, RA) was much higher than in the ventricles (RV, LV). By using two-way ANOVA we found no statistical differences between corresponding compartments of SD and LE rats. Immunohistochemical studies showed that OTR staining is not related to neuronal tissue and findings from left atrium indicate that prevalent localization of OTR is on cell membranes of cardiomyocytes.

CONCLUSIONS: The finding of expression of OTR mRNA by real-time qPCR and proof of OTR staining by immunohistochemistry in all heart compartments indicate that OT and its receptors may have function as a cardiovascular hormone. The differences in the HPA axis activity, as is exemplified in Sprague-Dawley and Lewis rat strain, do not project in the expression of OTR mRNA under basal condition. The effect of activity of HPA on OTR expression should be studied under stimulated conditions as it was performed in the behavioral studies....

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Journal Article 2011; 32(6): 763-768 PubMed PMID: 22286787 Citation  Keywords:  Animals, Dehydration:physiopathology, Glucose Transport Proteins, Facilitative:metabolism, Glutamic Acid:metabolism, Male, Paraventricular Hypothalamic Nucleus:metabolism, Rats, Rats, Sprague-Dawley, Sodium:metabolism, Synaptosomes:metabolism, Water Depri.   

OBJECTIVES: The purpose of this study was to identify and characterize Na+-dependent, high affinity glutamate transporter (GLUT) activity in the hypothalamic paraventricular nucleus (PVN) and to compare GLUT activity in PVN of euhydrated versus water-deprived rats.

METHODS: Sprague-Dawley rats were deprived of water for two days before sacrifice. Control rats received water ad libitum. After sacrifice, PVN and cerebrum were removed and synaptosomes were prepared using standard techniques. Glutamate uptake was measured using [3H]-glutamate as substrate, physiological buffer, approximately 100 µg of synaptosomal tissue per assay and a Brandel cell harvester.

RESULTS: Glutamate uptake was saturable in PVN synaptosomes from euhydrated, control rats with a Vmax of 541 ± 22 pmol/min-mg protein (SEM) and Km of 17.6 ± 3.8 µM (SEM). In contrast, Vmax of glutamate uptake was 808 ± 58 pmol/min-mg protein in PVN of rats deprived of water for 2 days. This was significantly higher than controls (p<0.001). Km was 21.2 ± 7.3 µM and not significantly different from controls (NS).

CONCLUSIONS: Our results suggest that water deprivation of rats results in significantly higher synaptosomal glutamate uptake in PVN. Although the exact mechanism is unknown, increased transcription of the GLUT gene and/or increased cell surface expression of GLUT may contribute to the observed increase of glutamate uptake in dehydrated rats. Increased glutamate uptake may serve to restrict dehydration-induced activation of PVN efferent pathways specifically involved in release of neurohypophysial hormones and activation of sympathetic outflow that operate to maintain body fluid balance and cardiovascular function....

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