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Journal Article 2010; 31(5): 609-615 PubMed PMID: 21173750 Citation  Keywords:  Animals, Disease Models, Animal, Immunohistochemistry, Injections, Intraperitoneal, Injections, Intraventricular, Interleukin-1beta, Lipopolysaccharides, Male, Neuronal Plasticity, Neuropeptides:biosynthesis, Paraventricular Hypothalamic Nucleus:immunolog.   

OBJECTIVES AND METHODS: Neuropeptides, as the main neuroendocrine system effectors, regulate notably the response to different stressors via a secretory plasticity within their respective hypothalamic neuronal populations. The aim of the present study was to explore by immunocytochemistry the occurrence and the potential expression plasticity of the novel neuropeptide EM66 in the CRH neurones of stressed rats.

RESULTS: The secretogranin II (SgII)-derived peptide EM66 is strongly expressed within hypothalamic neuroendocrine areas such as the parvocellular aspect of the paraventricular nucleus (pPVN) as well as the median eminence, suggesting a probable hypophysiotropic effect of this peptide. As a first approach to investigate such a role, we evaluated by immunohistochemistry EM66 expression within the pPVN following acute immune stress induced by lipopolysaccharide (LPS) or interleukin-1β (IL-1β) injection in rat. This study showed that EM66 is present in the pPVN but the number of EM66 immunolabeled cells did not fluctuate in this structure following LPS peripheral injection. In line with this observation, an intracerebroventricular injection of IL-1β did not provoke any significant variation of the number of intraparaventricular EM66 neurones.

CONCLUSION: The present data revealed for the first time that EM66 expression would be insensitive to the central and peripheral cytokines within the neurosecretory hypothalamic pPVN. This result indicates that EM66 does not participate to the phenotypic plasticity of hypothalamic parvicellular neurones in response to acute inflammatory stress....

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Journal Article 2010; 31(1): 103-112 PubMed PMID: 20150881 Citation  Keywords:  Animals, Female, GABA Antagonists:pharmacology, Ganglia, Sympathetic:drug effects, Gonadal Hormones:secretion, Nerve Growth Factor:metabolism, Neuropeptides:pharmacology, Nitric Oxide:metabolism, Nitric Oxide Synthase Type II:metabolism, Norepinephrine:ph.   

OBJECTIVE: Ovarian steroids are modulated by neural influences. In this work we investigate whether norepinephrine (NE) modifies the vasoactive intestinal peptide (VIP) or neuropeptide Y (NPY) actions in coeliac ganglion (CG) on the ovarian hormone release, and evaluate the participation of nitric oxide (NO), measured as nitrite, and of inducible nitric oxide synthetase (iNOS) protein, nerve growth factor (NGF) and its trkA receptor gene expression in the ovarian response.

METHODS: The study was performed in the ex vivo CG-superior ovarian nerve (SON)-ovary system of rats on diestrus day 2 (D2). CG and ovary were placed in separate compartments connected by the SON and incubated with Krebs-Ringer buffer. After addition of 50 ng/ml VIP, 50 ng/ml NPY, 10-6 M NE, or a mix of VIP+NE or NPY+NE in ganglion, samples from the ovarian compartment were taken at different times throughout 180 minutes to measure progesterone, androstenedione and nitrite levels.

RESULTS: VIP and NPY in ganglion induced an increase of progesterone release that was associated for VIP, but not NPY, with a decrease of ovarian nitrite levels, iNOS protein, and NGF/trkA receptor mRNA expression. By contrast, NE in ganglion decreased progesterone, an effect that was suppressed by addition of propranolol in ganglion, and increased nitrites/iNOS and NGF/trkA receptor expression in ovary. GABA A receptor antagonist bicuculline (20 muM) added in ovarian compartment prevented the inhibitory effect on progesterone caused by NE in CG. Androstenedione was not modified under neuropeptides or NE ganglionic stimulation.

CONCLUSIONS: Finally, results from VIP+NE or NPY+NE in ganglion showed that ovarian response on D2 induced by VIP or NPY alone is moderated by the opposite action of NE, and occurs only on progesterone, the most sensitive steroid to neural action....

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Journal Article 2010; 31(1): 97-102 PubMed PMID: 20150879 Citation  Keywords:  Age of Onset, Case-Control Studies, Depressive Disorder:epidemiology, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Intracellular Signaling Peptides and Proteins, Male, Memory Disorders:genetics, Phosphoproteins, Polymorphis.   

OBJECTIVE: Depression is a disease of multifactor background. Episodic memory dysfunction is one of depression characterising disturbances, which may lead to its onset and development. Memory processes are controlled by a number of extra- and intracellular mechanisms. KIBRA, a newly discovered protein, belonging to signal transduction proteins, participates in the control of episodic memory. The presented study was designed to assess correlation between single nucleotide polymorphism (SNP) T/C (rs17070145) of the KIBRA gene and the risk of recurrent depressive disorder (DD).

METHODS: The study was carried out in a group of 181 patients with recurrent DD and 149 healthy control subjects. Genotyping was conducted by polymerase chain reaction (PCR)/restriction fragment length polymorphism (RLFP) method.

RESULTS: TThe obtained results have revealed no significant correlation between the studied polymorphism and recurrent DD. Obtained value of the disease odds ratio (ORdis) suggests that presence of T/T homozygote decreases risk of development of recurrent DD, but the result was not statistically significant.

CONCLUSIONS: Following the results, it may be concluded that the studied polymorphism does not influence either the onset mechanism or the course of recurrent DD. Even if T/C polymorphism of the KIBRA gene induces memory disturbances, they may be unspecific and unselective for recurrent DD. Further studies on the genes, which control characteristic processes of DD and influence their course, are demanded and mostly justified....

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Comparative Study 2009; 30(1): 46-50 PubMed PMID: 19300398 Citation  Keywords:  Amyloid beta-Peptides:blood, Animals, Brain:metabolism, Guinea Pigs, Kidney:metabolism, Male, Orchiectomy, Testosterone:metabolism, Time Factors,.   

OBJECTIVES: The association between low testosterone levels and Alzheimer's disease (AD) amyloid beta-peptide (Abeta) metabolism was investigated in brain and kidney of guinea pigs.

METHODS: The expression of Abeta peptide in the brain and kidney was assessed by using the immunohistochemistry method.

RESULTS: No expression of Abeta was seen in both groups of animals. This negative staining was found until the fourth week following castration. The formation of Abeta in guinea pigs is perhaps not a short duration process and may undergo different metabolic pathway compare to humans.

CONCLUSION: castration was not associated with the formation of Abeta in the brain and kidneys during a 1-month period and might require a longer period of time....

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Journal Article 2009; 30(5): 647-651 PubMed PMID: 20035270 Citation  Keywords:  Adolescent, Adult, Aged, Aged, 80 and over, Alzheimer Disease:cerebrospinal fluid, Amyloid beta-Peptides:cerebrospinal fluid, Biomarkers:cerebrospinal fluid, Cerebral Ventricles:chemistry, Child, Child, Preschool, Female, Humans, Hydrocephalus:cerebrospin.   

OBJECTIVE: Determination of various biomarkers, such as beta-amyloid, tau-protein, phosphorylated tau-protein in CSF and their sensitivity and specificity in neurodegenerative brain processes, in particular Alzheimer Dementia (AD), has been recently investigated to monitor their abnormalities in the CSF at early stages of diseases before the clinical manifestation.

DESIGN AND SETTING: In the pilot group of our patients (10 men / 5 women) who underwent a drainage neurosurgical procedure for diagnosis of hydrocephalus, CSF was obtained from the brain ventricles and the influence of a different compartment of the CSF on the level of biomarkers, tau-protein and beta-amyloid, was investigated.

RESULTS: The mean tau-protein level for all 15 patients was 812.0 pg/ml, with median value 363.7 pg/ml; while mean beta-amyloid level for all 15 patients was 526.7 pg/ml, with median value 239.5 pg/ml, respectively. The abnormal tau-protein and beta-amyloid levels were found in the subgroup of patients in whom hydrocephalus was caused by a severe pathological process, such as brain tumor. The beta-amyloid values were significantly lower also in comparison with our previously published results in patients with AD in the CSF obtained by lumbar puncture in the spinal canal.

CONCLUSIONS: CSF in the brain ventricles is theoretically more stable and the values in this CSF probably provide more reliable informations for clinical diagnostic procedure than those for the CSF obtained by lumbar puncture in the spinal canal....

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Journal Article 2009; 30(Suppl 1): 13-16 PubMed PMID: 20027136 Citation  Keywords:  Animals, Bacterial Toxins:toxicity, Cyanobacteria:metabolism, Fishes:immunology, Liver:drug effects, Microcystins:toxicity, Neurosecretory Systems:drug effects, Peptides, Cyclic:toxicity, Uracil:analogs & derivatives,.   

: Cyanotoxins are the metabolites of cyanobacteria, belonging to different chemical groups and of diverse mechanisms of toxicity. Generally, they are divided into hepatotoxins, neurotoxins and dermatotoxins/irritant toxins. There is a growing evidence, that besides the above mentioned toxicity, exposure to cyanotoxins may also induce other effects, among others the disruption of neuroendocrine and immune systems. The purpose of that paper is to sum up the current information obtained from the literature and from our own studies about the influence of cyanohepatotoxins on neuroendocrine and immune systems of fish. From the presented data it appears, that microcystins, nodularin and cylindrospermopsin, except for their hepatotoxic activity, are potent to exert such effects as HPI axis activation resulting in physiological and behavioural changes, disturbances in thyroid hormones release/metabolism, as well as impairment of immune responses in fish. However the studies in that area are still incomplete and many questions remain to be answered, especially what consequences for fish population health status it brings....

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Comparative Study 2008; 29(6): 917-923 PubMed PMID: 19112412 Citation  Keywords:  Animals, Behavior, Animal:drug effects, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Interactions, Exploratory Behavior:drug effects, Male, Motor Activity:drug effects, Neuropeptides:administration & dosage, Neuroprotective Agents:.   

OBJECTIVES: On the animal model of trimethyltin (TMT) induced behavioral deficits the effect of chronic treatment with spirocyclic dipeptide cyclo/alanyl-l-amino-l-cyclopentane-carbonyl (alaptide, AL) was evaluated in adult male rats.

METHODS: Changes in the spontaneous behavioral repertoire were investigated in the open-field test on Day 21 (Session 1) and Day 28 (Session 2) after a single oral TMT administration.

RESULTS: In Experiment 1, rats given the highest TMT dose (7.5 mg/kg) exhibited significantly increased total number of behavioral patterns, the floor sniffing being the most frequent pattern. While the medium TMT dose (5 mg/kg) had a similar effect only in Session 1, the lowest TMT dose (2.5 mg/kg) was entirely ineffective. In Experiment 2, an explicit beneficial influence of both AL doses (5 and 10 mg/kg) given for 10 days before and 10 days after TMT (7.5 mg/kg) on the spontaneous behavior repertoire was observed in both Session 1 and Session 2. The total number of patterns and the time spent in individual patterns of AL+TMT treated animals did not differ from the controls and those given AL alone.

CONCLUSION: We conclude that sufficiently long AL treatment interfered with deleterious effects of TMT and forestalled changes in the structure and timing of spontaneous behavioral patterns. Thus, AL can be designated as a substance having "neuroprotective" effects....

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Comparative Study 2008; 29(6): 971-976 PubMed PMID: 19112391 Citation  Keywords:  Adolescent, Adult, Amyloid beta-Peptides:cerebrospinal fluid, Biomarkers:cerebrospinal fluid, Case-Control Studies, Demyelinating Diseases:cerebrospinal fluid, Female, Humans, Male, Middle Aged, Multiple Sclerosis:cerebrospinal fluid, Peptide Fragments:ce.   

OBJECTIVES: The presented study focuses on the importance of measurement of beta-amyloid42 (Abeta-42) levels, total tau protein, and phosphorylated tau (p-tau) protein in the cerebrospinal fluid (CSF) of cerebrospinal multiple sclerosis (MS) and clinically isolated syndrome (CIS) which represents an early phase of multiple sclerosis.

METHODS: A total of 23 patients with clinically isolated syndrome and suspected MS were enrolled into the study. Of this number, 14 patients met the criteria for definitive MS according to McDonald. The control group consisted of 40 patients examined for the possibility of organic damage to the brain, which was not confirmed. We used method of enzyme immunoanalysis to examine concentrations of tau protein, p- tau protein, and beta amyloid42. Differences between the respective groups were examined by test statistics. In addition, dependence of the total tau protein, p-tau protein, and beta-amyloid42 levels on demographic variables, diagnosis and duration of disease was examined by correlation analysis. Correlation of the concentrations obtained in the measurements was evaluated based on the calculated correlation coefficient (r) and level of significance (p).

RESULTS: Compared to the control group, no statistically significant difference was found in the levels of tau protein and p-tau protein between the CIS group and definitive MS group. A significant increase was found only for beta-amyloid42 levels in patients with diagnosed MS vs. control group. We demonstrated no correlation between the beta-amyloid42 and tau protein levels, p-tau protein and age of patients and duration of disease in patients with MS, CIS and the control group.

CONCLUSION: Results of our study show that use of tau protein, p-tau protein and beta-amyloid42 in the diagnosis of multiple sclerosis seems to be non-beneficial. We confirmed no importance for the differential diagnosis of an early stage MS....

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