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Journal Article 2005; 26(3): 237-241 PubMed PMID: 15990728 Citation  Keywords:  Animals, DNA:chemistry, Entropy, Evolution, Molecular, Humans, Models, Chemical, Nucleic Acid Conformation, Peptides:chemistry, Promoter Regions, Genetic, Protein Binding, Protein Conformation, Transcription Factors:chemistry,.   

PROBLEM: Gerontology observations show that ageing of organism is accompanied by the decrease of the chromatin activity and slowing down of the protein synthesis. Natural regulatory oligopeptides and their synthetic analogues take part in the activation of chromatin and normalise rate of the protein synthesis in cultured tissues. Regulatory peptides significantly enhance longevity.

OBJECTIVES: The objective of this work is to find a possible molecular mechanism by which the regulatory peptides influence the part of genetic system is responsible for initiation of protein synthesis in higher organisms.

METHODS: An interdisciplinary approach was used to address the problem. The work involved not only medical scientists and biologists, but also specialists in biopolymer chemistry, and mathematicians for statistical analysis of information interaction of amino acid and nucleotide sequences.

CONCLUSIONS: The structures and metrics of peptides and the DNA double-helix cause the recognition and complementary binding of a regulatory peptide with DNA functional groups at the interface of the major groove. We have used complementary binding model to find a possible base pair sequence ATTTTC for specific binding of synthetic tetrapeptide epitalon. This base pair block and its reverse complement were found repeatedly in the promoter region of telomerase. A comparison of statistical information content of peptides and oligonucleotide sequences shows that these two classes of biopolymers are information carriers and. exchange the information to initiate the gene transcription....

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Journal Article 2005; 26(3): 231-236 PubMed PMID: 15990727 Citation  Keywords:  Animals, Brain Chemistry:immunology, Cell Extracts:chemistry, Cytokines:analysis, Detergents, Enzyme-Linked Immunosorbent Assay:methods, Interferon-gamma:analysis, Interleukin-10:analysis, Kidney:chemistry, Lipopolysaccharides:pharmacology, Liver:chemistr.   

OBJECTIVES: Determination of protein cytokines in local tissues would help to evaluate their local role in health, sickness behavior and immune-mediated diseases. Therefore, developing a simple quantitative method of protein cytokines in tissues/organs is highly important.

METHODS: Mouse tissues were collected following intraperitoneal administration of endotoxin-free PBS or lipopolysaccharide. A mild detergent, 0.1% Igepal, was added in a buffer to enhance cytokines extraction. The tissues were then disrupted, homogenized, centrifuged and the supernatants were collected and assayed using solid-phase immunoassays.

RESULTS: The presence of 0.1% Igepal extracted significantly more TNF-alpha from liver (322%: p<0.01), brain (358%: p<0.05), lungs (1600%: p<0.01), and more IL-10 from liver (220%: p<0.001), brain (4650%: p<0.001) than PBS alone. On the other hand, using 0.1% Igepal did not increase IFN-gamma extraction from liver, spleen, brain, lungs, skin and kidneys more than PBS alone. Furthermore, i.p. administration of LPS induced a differential milieu of cytokines. LPS increased significantly the production of TNF-alpha, IFN-gamma, and IL-10 from liver (521%, 123%, 72%: p<0.01, 0.04, 0.04), brain (470%, 122%, 280%: p< 0.01, 0.03, 0.01), peritoneal lavage (p<0.001) and blood (p<0.001). However, the pattern of increase was different for the above cytokines in spleen, skin, lungs and kidneys.

CONCLUSIONS: The extraction of protein cytokines from tissues was superior with addition of mild detergent. Furthermore, our results showed a differential cytokines response to LPS with respect to tissue and cytokine type. This method should provide an important tool for studying local protein cytokines in behavioral pattern, sickness behavior, and immune-mediated diseases as well as to determine local therapeutic efficacy of immunomodulatory drugs....

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Journal Article 2005; 26(3): 225-230 PubMed PMID: 15990726 Citation  Keywords:  Animals, Blood Glucose:drug effects, Cholinesterase Inhibitors:pharmacology, Denervation, Entorhinal Cortex:cytology, Excitatory Amino Acid Agonists, Hippocampus:cytology, Ibotenic Acid, Male, Microinjections, Neostigmine:pharmacology, Neural Pathways, Ra.   

OBJECTIVE: Microinjectin of neostigmine, an inhibitor of acetylcholine esterase, into the rat hippocampus elicited stress-like responses reflected by the release of adrenocorticotropic hormone (ACTH) and blood glucose elevations. The entorhinal cortex is regarded as an interface between the hippocampus and neocortex. The current study was designed to examine the role of the entorhinal cortex in regulation of blood glucose elevation induced by hippocampal neostigmine injection.

MATERIAL AND METHODS: We produced the entorhinal cortex lesions in 9 week-old male Wistar rats by the bilateral injections of the cell-selective neurotoxin, ibotenic acid (15microg/microl). Two weeks after the injections, neostigmine methylsulfate (sigma, 5x10(-8) mol) was microinjected into the rat hippocampus in a volume of 1microl for 1min using a CMA/100 microinjection pump. Plasma ACTH levels were measured by radioimmunoassay. Plasma glucose concentrations were determined by the immobilized enzyme membrane/H2O2 method with a compact glucose analyzer Antsense II (Bayer Medical Co.Ltd,Tokyo, Japan).

RESULTS: Compared with sham-operated control rats, the entorhinal lesions produced by ibotenic acid significantly attenuated the elevations of blood glucose evoked by the microinjection of neostigmine into the hippocampus. However, no significant difference of plasma ACTH in response to the injection was observed between the entorhinal-lesioned rats and controls.

CONCLUSION: The results of the present study indicate that the entorhinal cortex plays a role in the central nervous systems regulation of blood glucose and may be involved in a stress response presumably via an alternative pathway....

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Journal Article 2005; 26(3): 205-208 PubMed PMID: 15990722 Citation  Keywords:  Animals, Antipsychotic Agents:pharmacology, Dibenzothiazepines:pharmacology, Glucose:pharmacology, Insulin:metabolism, Islets of Langerhans:drug effects, Male, Organ Culture Techniques, Piperazines:pharmacology, Quetiapine Fumarate, Rats, Rats, Wistar, Ri.   

OBJECTIVE: In the light of the recent finding that the atypical antipsychotics clozapine and olanzapine have a stimulatory effect on basal insulin release in vitro, the influence on insulin release of three other atypical agents; quetiapine, risperidone and ziprasidone, was examined.

METHODS: The effect of each atypical antipsychotic in a concentration of 10(-6) M was investigated on both basal and glucose-stimulated insulin release from isolated rat pancreatic islets.

RESULTS: No difference in effect on insulin release was found for any of the three atypical antipsychotic substances compared to controls without antipsychotics, either in basal or in glucose-stimulated insulin release.

CONCLUSION: This study demonstrates that the main compounds of quetiapine, risperidone and ziprasidone do not increase insulin release from isolated pancreatic islets, which stands in clear contrast to what has been found previously for clozapine and olanzapine. Thus, atypical antipsychotics seem to differ in their effect on insulin release in vitro....

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Journal Article 2005; 26(3): 197-203 PubMed PMID: 15990721 Citation  Keywords:  Aging:physiology, Animals, Antibodies, Blood Pressure:physiology, Body Temperature:physiology, Caloric Restriction, Cell Survival:physiology, Estrogen Receptor alpha:immunology, Female, Immunohistochemistry, Luteinizing Hormone:metabolism, Mice, Mice, Inb.   

: Life-long calorie restriction (CR) remains the most robust and reliable means of extending life span in mammals. Among the several theories to explain CR actions, one variant of the neuroendocrine theories of aging postulates that changing hypothalamic sensitivity to endocrine feedback is the clock that times phenotypic change over the life span. If the feedback sensitivity hypothesis is correct, CR animals should display a significantly different pattern of hormone-sensitive cell density and distribution in the hypothalamus. Of the many endocrine signal receptors that may be involved in maintaining hypothalamic feedback sensitivity, our study has selected to begin mapping those for estrogen (E). Altered hypothalamic sensitivity to E is known to schedule reproductive maturation and influence reproductive senescence. Taking estrogen receptor-alpha (ERalpha) immunoreactivity as an index of sensitivity to E, we counted ERalpha immunoreactive and non-immunoreactive cells in the pre-optic hypothalamus of young (6 weeks), ad-libitum (Old-AL) fed old (22 months), and calorie restricted (Old-CR) old (22 months) female B6D2F1 mice. An automated imaging microscopy system (AIMS) was used to generate cell counts for each sampled section of pre-optic hypothalamus. Results show a 38% reduction in ERalpha immunoreactive cells and an 18% reduction in total cell numbers in AL-old mice in comparison to young mice. However, CR mice only show a 19% reduction in ERalpha immunoreactive cells and a 13% reduction in total cell numbers in comparison to young mice. This indicates CR prevents age-related cell loss and maintains estrogen sensitivity in the pre-optic hypothalamus of old female B6D2F1 mice....

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Journal Article 2005; 26(3): 193-195 PubMed PMID: 15990720 Citation  Keywords:  Adrenal Cortex:cytology, Animals, Biological Clocks:physiology, Cell Aging:physiology, Humans,.   

: It is well known that plasma levels of dehydroepiandrosterone (DHEA), a steroid hormone secreted by zona reticularis (ZR) of the adrenal cortex, reach the maximal values in the third decade of life and then gradually decline with age. Moreover, the DHEA deficiency is probably responsible for several functional disturbances connected with aging. It was also found that ZR reaches its definitive volume at puberty and undergoes selective atrophy during the aging. Thus, the decline of DHEA may be a simple consequence of ZR atrophy in aged subjects. A hypothesis presented here attempts to explain the mechanism of the age-related ZR atrophy and is based on the adrenal cortex cell kinetics. In the adrenal cortex the cell proliferation indices are lower when we pass from zona glomerulosa (ZG) to the inner zones and are the lowest in ZR. In contrast, the apoptotic index is the highest in ZR. It is suggested that adrenocortical cells renew from the progenitor cells located in ZG /zona fasculata boundary and /or in subcapsular layer. These cells migrate centripetally undergoing the subsequent steps of differention and consecutive divisions - and - if not die en route - reach the most central localization in ZR. In consequence, ZR includes the "oldest" adrenocortical cells which probably in majority reached the "Hayflick's number" and cannot divide. This results in the preponderance of apoptosis over proliferation leading to progressive ZR atrophy followed by a decline of secretion of ZR-derived steroid hormones....

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Comparative Study 2005; 26(2): 125-130 PubMed PMID: 15855883 Citation  Keywords:  Action Potentials:physiology, Animals, DNA-Binding Proteins:metabolism, Electrophysiology, Hypothalamus:cytology, In Vitro Techniques, Male, Milk Proteins:metabolism, Neurons:metabolism, Prolactin:physiology, Rats, Rats, Wistar, Receptors, Prolactin:metab.   

OBJECTIVES: The study investigated the role of prolactin (PRL) in modulating STAT5 and electrical activity of magnocellular neurones in the supraoptic (SO) nucleus of male rats.

METHODS: Evidence of expression of STAT5 in the SO nucleus was investigated by immunocytochemical methods. Effect of blocking prolactin receptors on STAT 5 expression was investigated by Western blotting following transfection of SO neurones with a dominant negative mutant form of the PRL receptor. Prolactin-induced changes in electrical activity were investigated by extracellular recording in hypothalamic slices.

RESULTS: A high proportion of SO neurones in male rats expressed immunoreactive STAT5. Levels of activated STAT5 within the SO nucleus of PRL-treated rats was reduced following transfection with a dominant negative mutant form of the PRL receptor, as compared to rats transfected with wild type PRL receptor. Electrophysiological recordings from the SO nucleus in horizontal brain slices showed that approximately 25% of neurones were responsive to PRL, with both inhibitory and excitatory effects being observed. Cells displaying PRL responses included pharmacologically-identified oxytocinergic neurones.

CONCLUSIONS: Collectively, the results suggest that central PRL targets neurones of the SO nucleus, influencing both activation of the JAK-STAT signalling pathway and neuronal excitability. Whilst the functional significance of this interaction remains to be established, it might be important in co-ordinating oxytocin secretion with physiological events associated with changes in plasma PRL, or in mediating a feedback loop in the oxytocinergic regulation of lactotrophs....

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Comparative Study 2005; 26(2): 121-124 PubMed PMID: 15855882 Citation  Keywords:  Animals, Exploratory Behavior:drug effects, Female, Habituation, Psychophysiologic:drug effects, Male, Motor Activity:drug effects, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Sex Factors, Testosterone:pharmacology, Vocalization, Animal:drug effec.   

OBJECTIVES: The purpose of the present study was to characterize the influence of testosterone administered to pregnant females on offsprings postnatal behavioral strategies in the open field.

METHODS: The influence of maternal testosterone on behaviour of 23 day old male and female offsprings was studied in a 20-minute open field test. A total of 9 behavioural events were compared between a control (male n=12, female n=8) and a testosterone group (male n=9, female n=9). Dynamics and patterns of association of these behavioural events were analyzed. The testosterone group was prenatally exposed to testosterone (a single intramuscular injection of 2.5 mg testosteroni isobutyras on gestation day 14).

RESULTS: Male offsprings exposed prenatally to testosterone displayed significantly high levels of ambulation (P<0.05), sniffing (P<0.01), sniffing the air (P<0.05), urination (P<0.05) and significantly lower level of vocalization (P<0.05) than control. Female offsprings exposed prenatally to testosterone displayed significantly higher level of sniffing the air (P<0.05) than control. Significant differences in the dynamics of habituation process were registered only in the group of male. They were from 5 to 10 min in ambulation (P<0.05), from 10 to 15 min in sniffing (P<0.05) and vocalization (P<0.05), from 10 to 15 min and from 15 to 20 min in sniffing the air (P<0.05) and from 0 to 5 min in defecation (P<0.05) and urination (P<0.01).

CONCLUSION: Our results suggest that maternal testosterone may influence especially male postnatal open field strategies....

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