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Journal Article 2014; 35(1): 13-19 PubMed PMID: 24625911 Citation  Keywords:  Actins:chemistry, Animals, Brain-Derived Neurotrophic Factor:physiology, Female, Hippocampus:cytology, Interleukin-1beta:physiology, NF-kappa B:antagonists & inhibitors, Neurons:cytology, Rats, Rats, Wistar, Signal Transduction:physiology,.   

OBJECTIVES: To examine the effect of BDNF on F-actin during the stimulation of IL-1β in hippocampal neurons.

MATERIALS & METHODS: We cultured hippocampal neurons from rat embryos. Cell stimulation was induced by IL-1β. Cell culture success was evaluated by an activity analysis of CCK-8, staining of gliocyte by immunohistochemistry. Changes in F-actin, BDNF and NF-ĸB were examined using molecular analyses.

RESULTS: Our results demonstrate that a high concentration of IL-1β exaggerates the stimulation-induced degradation of F-actin by BDNF, whereas a low concentration of IL-1β protects F-actin against this degradation. These beneficial effects might be associated with the inhibition or exaggeration of the NF-ĸB signaling cascade.

CONCLUSIONS: Taken together, our findings indicate that BDNF acts as an F-actin-protective regulator during stimulation by IL-1β and that this function largely occurs via the regulation of NF- ĸB signaling. These results suggest that interventions targeting the BDNF signaling system may be of therapeutic value against major depressive disorder (MDD)....

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Journal Article 2013; 34(6): 543-548 PubMed PMID: 24378445 Citation  Keywords:  Age Factors, Animals, Animals, Newborn, Body Weight:physiology, Energy Metabolism:physiology, Estrogen Receptor alpha:blood, Female, Food Deprivation:physiology, Hypothalamus:growth & development, Leptin:blood, Pregnancy, RNA, Messenger:metabolism, Rats,.   

OBJECTIVE: Estrogen plays an important role in feeding and energy balance, and the critical role of estrogen in the control of appetite and energy balance is mediated by hypothalamic estrogen receptor (ER) alpha. In undernourished rodents, hypothalamic ER alpha mRNA expression are decreased. Responses of some hypothalamic factors to negative energy balance develop during the early neonatal period.

DESIGN: In this study, we examined the developmental changes of fasting-induced alterations in hypothalamic ER alpha mRNA expression in female rats.

RESULTS: ER alpha mRNA expression was reduced after a 12-h or 24-h fast at postnatal days 15 and 25, but not at day 5. Serum estradiol levels in postnatal day 25 rats were not changed by fasting. Although serum leptin levels were suppressed by fasting at all ages, hypothalamic ER alpha mRNA expression at postnatal day 25 was not changed by leptin administration after a 24-h fast.

CONCLUSIONS: These data show that the sensitivity of hypothalamic ER alpha to negative energy balance may not be established in the early neonatal period, and that it develops by postnatal day 15. Decreased leptin levels might not be involved in the alterations of hypothalamic ER alpha mRNA expression in the undernourished condition....

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Comparative Study 2013; 34(Suppl 2): 55-63 PubMed PMID: 24362093 Citation  Keywords:  Animals, Benzo(a)pyrene:metabolism, Carcinogens:metabolism, Cytochrome P-450 CYP1A1:metabolism, Cytochromes b5:pharmacology, Humans, Inactivation, Metabolic, Male, Microsomes, Liver:drug effects, Oxidation-Reduction, Rats,.   

OBJECTIVES: Cytochrome P450 (CYP) 1A1 is the most important enzyme in both activation and detoxification of carcinogenic benzo[a]pyrene (BaP), in combination with microsomal epoxide hydrolase (mEH). To evaluate metabolism of BaP in human, identification of a suitable animal model that mimics the metabolic fate of BaP in human is of great importance. The aim of this work was to compare BaP oxidation by human CYP1A1 and CYP1A1 of one animal model, rat. Investigation of the effect of cytochrome b5 on BaP oxidation by CYP1A1 was another target of this study.

METHODS: High performance liquid chromatography (HPLC) was employed for separation of BaP metabolites formed by enzymatic systems. Their structures were identified by mass- and NMR-spectrometry.

RESULTS: Human hepatic microsomes oxidized BaP to BaP-9,10-dihydrodiol, BaP-4,5-dihydrodiol, BaP-7,8-dihydrodiol, BaP-1,6-dione, BaP-3,6-dione and BaP-3-ol. The same metabolites were generated by rat liver microsomes, but BaP-9-ol and a metabolite Mx, the structure of which has not been identified as yet, were also formed in these microsomes. Human CYP1A1 expressed with NADPH:CYP reductase (POR) in Supersomes™ oxidized BaP to the same metabolites as microsomes, but BaP-4,5-dihydrodiol has not been detected. Rat recombinant CYP1A1 in this SupersomesTM system oxidized BaP to BaP-9,10-dihydrodiol, a metabolite Mx, BaP-4,5-dihydrodiol, BaP-7,8-dihydrodiol, BaP-1,6-dione, BaP-3,6-dione, BaP-9-ol and BaP-3-ol. Addition of cytochrome b5 to rat and human recombinant CYP1A1 systems led to a more than 2-fold increase in BaP oxidation.

CONCLUSION: The results show similarities between human and rat CYP1A1 in BaP oxidation and demonstrate rats as a suitable model mimicking BaP oxidation in human....

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Journal Article 2013; 34(Suppl 2): 11-20 PubMed PMID: 24362087 Citation  Keywords:  Animals, Carcinogens:toxicity, Cyanobacteria:chemistry, Food Chain, Kidney:drug effects, Liver:drug effects, Male, Microcystins:toxicity, Rats, Rats, Wistar, Spleen:drug effects,.   

OBJECTIVES: Cyanobacteria are producers of potent and environmentally abundant microcystins, representing an emerging global health issue. In the present study, we investigated the impact of pure microcystins and cyanobacterial biomass on laboratory rats (Wistar albino rats, males, 30 days old) under different exposure scenarios.

METHODS: The rats were fed diets containing fish meat with microcystins in various concentrations and forms (cyanobacterial biomass and isolated microcystins) for 28 days.

RESULTS: Although considerable amounts of microcystins (MCs) were administered to the rats, all levels of MCs in the liver were close to the detection limit (3-5 ng/g fresh weight) using liquid chromatography - tandem mass spectrometry. Only rats exposed to cyanobacterial biomass had clearly higher hepatic and splenic somatic indexes while markers of oxidative stress (glutathione-S-transferase, glutathione reductase, lipid peroxidatio) were significantly increased in the group exposed to the high dose of MCs. Most of the analysed biochemical parameters did not show clear differences among groups. Levels of bilirubin and lipases were significantly increased only after exposure to cyanobacterial biomass and MCs, respectively. Considering microscopic findings in the liver, kidney, thymus, spleen and brain, histopathology was dominated by alterations in the hepatic parenchyma and renal cortical tubular system.

CONCLUSIONS: The present study demonstrates that oral exposure to MCs and cyanobacterial biomass may induce biochemical and detoxification responses associated with damage to liver and kidneys and in the laboratory rat....

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Journal Article 2013; 34(5): 383-387 PubMed PMID: 23922048 Citation  Keywords:  Animals, Autonomic Nervous System:drug effects, Cholinesterase Inhibitors:pharmacology, Heart Rate:drug effects, Indans:pharmacology, Male, Piperidines:pharmacology, Rats, Rats, Wistar,.   

OBJECTIVE: Donepezil, a cholinesterase inhibitor (ChEI) that is widely used to treat Alzheimer's disease, is thought to act by increasing extracellular acethylcholine (ACh) in the central nervous system. The effects of the administration of ChEIs on the autonomic nervous system, however, are complex and controversial.

METHODS: In this study we observed the effects of donepezil at a dose of 3 mg/kg intraperitoneally (i.p.) on the autonomic nervous system for two weeks using heart rate variability (HRV). In HRV, the high frequency (HF) band is influenced by cardiac parasympathetic tone, and the low frequency (LF) band is influenced by both sympathetic and parasympathetic activity. The ratio of LF and HF (LF/HF) is used for the assessment of the sympathetic nervous system.

RESULTS: In the current study the LF/HF was found to be significantly increased by day 1, but the magnitude of the response gradually decreased. The absolute power of HF increased after an i.p of donepezil of 3 mg daily in groups treated for 1 week and for 2 weeks compared to the single-dose groups.

CONCLUSION: Our results suggested that ChEI administration induced sympathetic nervous activation acutely, but chronic administration induced parasympathetic activation....

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Journal Article 2013; 34(5): 372-382 PubMed PMID: 23922044 Citation  Keywords:  Animals, Cell Line, Tumor, Cell Proliferation:drug effects, Dose-Response Relationship, Drug, Glucose:administration & dosage, Neurilemmoma:metabolism, Neurons:drug effects, Nitrosation:drug effects, Oxidative Stress:drug effects, Rats, Schwann Cells:drug.   

OBJECTIVE: One of the major complications during prolonged hyperglycemic condition is the onset of the so-called diabetic neuropathy, that can affect the peripheral nervous system. Evidence has reported that glucose-induced oxidative stress could be a key mediator in this process, impairing the cytoskeletal structures, such as microtubules. In general, much attention is paid to the possible nitrosative-induced changes of neurons during hyperglycemic conditions, while little is known of the Schwann cells.

METHODS: Using morphological examination, immunofluorescence staining and western blot analysis, the possible hyperglycemic oxidative-induced microtubular changes in the RT4 Schwannoma cell line was investigated.

RESULTS: After 72 hrs of 180 mM d-glucose exposure, a decrease of total, tyrosinated and detyrosinated α-tubulins was found, whereas a significant increase of the acetylated α-tubulin isotype and 3-nitro-l-tyrosine was present, both through western blot and immunofluorescence staining. Moreover a downregulation of catalase and deacetylase Sirt2 enzymes was detected.

CONCLUSION: Our data underline the importance of nitrosative-induced microtubular alterations in the PNS, during hyperglycemic conditions, highlighting that Schwann cells may be directly involved in the pathogenesis of diabetic neuropathy, through the impairment of their microtubular network....

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Journal Article 2013; 34(5): 418-425 PubMed PMID: 23922041 Citation  Keywords:  Animals, Glutathione Peroxidase:metabolism, Hippocampus:drug effects, Male, Malondialdehyde:metabolism, Melatonin:pharmacology, Oxidative Stress:drug effects, Pineal Gland:surgery, Rats, Rats, Wistar, Reactive Oxygen Species:metabolism, Superoxide Dismuta.   

OBJECTIVE: The effects of melatonin on antioxidant status were examined in pinealectomized rats using enzymatic, histological and immunohistochemical techniques. The aim of this study is to investigate the effects of melatonin on hippocampal apoptosis.

MATERIALS AND METHODS: Male Wistar rats (n=21) were divided into 3 groups: Group I and group II were designated as control (sham-pinealectomy) and pinealectomized rats, respectively. Rats in group III were pinealectomized and injected daily with melatonin (1 mg/kg) for 3 months beginning at day 7 after surgery. At the end of experimental period, all rats were killed by decapitation. The brains of the rats were removed and the hippocampus tissue was obtained from all brain specimens. The right hippocampal specimens of all rats were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels. The left hippocampus tissue specimens of all animals were used for immunohistochemical and histological evaluation.

RESULTS: The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in pinealectomized rats compared to the controls. In the histological and immunohistochemical evaluation of this group, increase of pyknotic cells, vacuolar degeneration and apoptosis were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats administered melatonin after pinealectomy. Furthermore, histological and apoptotic changes in hippocampus caused by pinealectomy were lost in the rats treated with melatonin.

CONCLUSIONS: The results of our study revealed that pinealectomy-induced oxidative damage and morphological changes in the hippocampal tissue were suppressed by melatonin.

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Journal Article 2013; 34(4): 314-321 PubMed PMID: 23803866 Citation  Keywords:  Animals, Body Weight, Corticosterone:metabolism, Diet, High-Fat, Feeding Behavior:physiology, Hypothalamo-Hypophyseal System:metabolism, Male, Pituitary-Adrenal System:metabolism, Proto-Oncogene Proteins c-fos:metabolism, Rats, Rats, Wistar, Solitary Nucl.   

OBJECTIVES: The brain and the gut communicate bi-directionally through the brain-gut axis. The key role in such interactions plays autonomic nervous system and its major component, the vagus nerve. There is growing evidence that vagus nerve stimulation (VNS) has a suppressive effect on both short- and long-term feeding in animal models. In the present study, we investigated the effect of VNS on the hypothalamic pituitary adrenal axis, feeding behavior and appetite in rats fed a high-fat diet.

METHODS: Adult male Wistar rats were implanted with a microstimulator (MS) and fed a high-fat diet throughout the study (42 days). The left vagus nerve was stimulated subdiaphragmatically by electrical pulses (10 ms, 200 mV, 1 Hz or 10 Hz respectively, 12 h a day) generated by the MS. Daily food intake and body weight were measured. At the end of the experiment, animals were euthanized and serum corticosterone levels were assessed by immunoassays. Adipose tissue content was evaluated by measuring epididymal fat pads' weight. To determine whether VNS activated food-related areas of the brain, neuronal c-Fos induction in the nucleus of the solitary tract (NTS) was assessed.

RESULTS: Chronic VNS decreased food intake, body weight gain and epididymal fat pad weight in stimulated animals compared to control animals. Serum corticosterone concentrations were significantly elevated following VNS, and neuronal responses in the NTS were observed.

CONCLUSIONS: The study demonstrates that chronic electrical VNS exerts anorexigenic effects on food intake and body weight gain, and the hypothalamic pituitary adrenal axis activation may contribute to these effects....

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