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Journal Article 2006; 27(1-2): 177-182 PubMed PMID: 16670672 Citation  Keywords:  Animals, Antigens:genetics, Cell Count, Cerebral Cortex:cytology, Female, Immunohistochemistry, Leptin:pharmacology, Mice, Mice, Inbred ICR, Oligodendroglia:drug effects, Pregnancy, Proteoglycans:genetics, Receptor, Platelet-Derived Growth Factor alpha:bi.   

OBJECTIVE: Leptin, which is an obese gene product, decreases appetite and increases energy expenditure in adults. In our previous study, leptin was found to maintain neural stem cells and/or progenitor cells, preferentially astrocyte/oligodendrocyte progenitor cells, whereas it reduces the proportion of oligodendrocyte lineage-restricted precursor cells. It has been reported that leptin-deficient (ob/ob) mice have lower levels of glial proteins than wild-type mice. These findings suggest that leptin affects the development of glial cells. In this study, therefore, we investigated oligodendrocyte development in the cerebral cortex of ob/ob and wild-type mouse embryos by histochemistry.

METHODS: We obtained ob/ob or wild-type (C57BL/6J) embryos on embryonic day (E) 18. We performed immunohistochemistry in the embryonic cerebrum with antibodies against NG2, platelet-derived growth factor receptor-alpha (PDGFR-alpha) and leptin receptor (Ob-R). In the cerebral cortex, we compared the number of the oligodendrocyte precursor cells (OPCs), which are immunopositive for NG2 and/or PDGFR-alpha, between ob/ob and wild-type embryos.

RESULTS: We revealed that ob/ob embryos had significantly more OPCs than wild-type embryos on E18. PDGFR-alpha-positive OPCs did not coexpress leptin receptor in the cerebral cortex.

CONCLUSION: These findings suggest that leptin inhibits differentiation of multipotent and/or glial progenitor cells into OPCs in the mouse embryonic cerebral cortex, but it does not directly act on OPCs....

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Journal Article 2006; 27(1-2): 21-33 PubMed PMID: 16648819 Citation  Keywords:  Diet, Eating:psychology, Food, Humans, Motivation, Receptors, Opioid, mu:physiology, Reward, Satiety Response:physiology,.   

: Over the last decades, the importance of food in the development of chronic diseases has been examined, as well as the medical value of eating healthy. The contribution of the eating process itself to health and well-being, however, has not been questioned until most recently. Biology has linked eating to appetitive motivational processes with their underlying neurophysiology, including CNS reward circuitries: Eating uses the pleasure-reward physiology to motivate us to eat. Endogenous opiates, such as morphine, insure our survival by helping us to make eating motivational via pleasure induction. After taking in enough food, we become satisfied, i.e., tolerant to food. Our appetite, and so is our appetence, are then low and need a certain time span to reach their former levels for then inducing food-seeking behaviors, food intake, etc. again. When tolerance passes, we once more engage in this pleasurable process related to positive behavioral motivation. Opioid receptor agonists, however, may induce energy intake even beyond an actual need. This interesting potential of opioidergic signaling may have its roots in biological mechanisms that insured the intake and storage of high energy foods, hence preparing for future famines. In our world of today, however, such neurobiological pathways may pose a threat on our health. Thus, feedback mechanisms, such as tolerance, aversion and satiety, have to be finely tuned. Therefore central autoregulation that involves, for example, limbic mu receptor signaling and other endogenous signaling compounds comes into the focus of modern science. The time where research recognizes the importance of neurobiological pathways such as endogenous opiate autoregulation or CNS reward circuitries for examining the physiology of food intake has yet begun. Many questions remain open and have to be answered through future scientific inquiry....

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Journal Article 2006; 27(1-2): 219-224 PubMed PMID: 16648810 Citation  Keywords:  3-Hydroxysteroid Dehydrogenases:genetics, Adrenal Cortex Hormones:metabolism, Alleles, Child, China:epidemiology, Female, Gene Frequency, Genotype, Gonadal Steroid Hormones:blood, Humans, Insulin Receptor Substrate Proteins, Molecular Sequence Data, Phosp.   

OBJECTIVES: In order to investigate whether the variances in the candidate genes (Insulin receptor substrate IRS-1, beta3-adrenergic receptor ADRB3, 3 beta-hydro-xysteroid dehydrogenase HSD3B2, glucocorticoid receptor GRL and 21-hydroxylase CYP21) which affect the metabolism of adrenal steroids hormone and body composition, are associated with precocious puberty in Chinese girls.

METHODS: PCR-RFLP analysis method was applied in the typing of six activity SNPs in five genes in two groups: 176 precocious puberty girls as case and 192 healthy girls as control.

RESULTS: The typing results showed that the frequencies of the allele CYP21 L282 polymorphism were 32.7% and 32.6% in case and control groups (P=0.518), respectively. For IRS-1 R972, they were 0.6% in cases and 2.3% in controls (P=0.043), for ADRB3 R64, 13.6% in cases and 12% in controls (P=0. 378), and for GRL S363, 7.4% in cases and 5.73% in controls (P=0.335). No sample in the two groups carries the variation of CYP21 I172N and HSD3B2 L236S.

CONCLUSION: Among these six activity SNPs in five candidate genes, IRS-1 972R was statistically associated with the onset time of puberty in Chinese girls. In order to confirm whether the candidate genes have any other activity SNPs that are associated with the onset time of puberty in Chinese girls, resequencing of these candidate genes is needed in following time....

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Journal Article 2006; 27(1-2): 236-240 PubMed PMID: 16648784 Citation  Keywords:  Adolescent, Alleles, Attention Deficit Disorder with Hyperactivity:epidemiology, Child, Czech Republic:epidemiology, DNA:genetics, Gene Frequency, Humans, Male, Polymorphism, Genetic, Psychiatric Status Rating Scales, Receptors, Dopamine D2:genetics, Reve.   

OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is a prevalent childhood disorder. Evidence from the family and twin studies suggest that ADHD is familiar and highly heritable. Association studies are frequently used for the searching of markers responsible for genetic basis of ADHD. We investigated TaqI polymorphism of the dopamine receptor D2 (DRD2) in relationship with ADHD. The association between TaqI A polymorphism of DRD2 gene and ADHD has previously been published.

DESIGN: We used the association study to test the relationship between TaqI A polymorphism of DRD2 gene and ADHD on groups of ADHD boys and control boys.

SETTING: For DNA isolation, buccal tissue was used. PCR with restriction analysis of PCR products was used for genotyping.

RESULTS: We found statistically different genotypic and allelic frequencies (p < 0.008, p < 0.002, respectively) of DRD2 polymorphism between two studied groups of boys.

MAIN FINDINGS: According to our results we suppose that polymorphism TaqI A of DRD2 gene is involved in the pathogenesis of childhood ADHD in male subjects. Allele A1 and genotype A1A1 in male subjects is associated with ADHD.

CONCLUSIONS: Our study confirmed the relationship between TaqI A polymorphism of DRD2 gene and ADHD published previously....

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Comparative Study 2005; 26(6): 729-732 PubMed PMID: 16380686 Citation  Keywords:  Age Factors, Animals, Animals, Newborn, Longitudinal Studies, Male, Organ Size:drug effects, Rats, Rats, Sprague-Dawley, Selective Estrogen Receptor Modulators:pharmacology, Sexual Behavior, Animal:drug effects, Tamoxifen:pharmacology, Testis:cytology, Te.   

OBJECTIVE: In this study we examined the possibility that demasculinization produced by the neonatal administration of tamoxifen is accompanied by a decline in plasma levels of testosterone during adulthood.

METHODS: Wistar male rats received either a treatment with 12.5 microg/kg of tamoxifen during the first eight days of age or a treatment with 100 microg/kg of tamoxifen for five days. Each treatment had their respective control group. During adulthood their masculine sexual behavior was analyzed. At 8 months of age, males were killed by decapitation, trunk blood was collected and peripheral glands were dissected and weighed. Testosterone levels were measured by HPLC. Histological analysis of peripheral glands was performed.

RESULTS: Both neonatal tamoxifen treatments significantly decreased male sexual behavior when compared to control values. In addition, both treatments also showed a significant decrease in testicular weight when compared to control groups, as well as a decrease in seminal vesicle weight. In the microscopic analysis, a significant decrease in the diameter of the seminiferous tubules was observed, especially in the animals treated with 100 microg/kg of tamoxifen. However, no differences were observed between tamoxifen treated and control animals concerning plasma levels of testosterone.

CONCLUSION: The present results indicate that behavioral manifestations and changes in peripheral reproductive organs that accompanied demasculinization are not due to a deficit in testosterone secretion....

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Journal Article 2005; 26(5): 526-532 PubMed PMID: 16264406 Citation  Keywords:  Animals, Astrocytes:drug effects, Blotting, Western, Cell Line, Estradiol:pharmacology, Estrogen Antagonists:pharmacology, Estrogen Receptor alpha:drug effects, Estrogen Receptor beta:drug effects, Gene Expression Regulation:drug effects, Ligands, Lucifer.   

OBJECTIVE: The mechanism through which estrogen exerts its neuroprotective and anti-neurodegenerative effects in the central nervous system is poorly understood. Human glial cells are implicated in the pathogenesis of Alzheimer's disease and have both alpha and beta estrogen receptors (ER). We developed a glial cell model for ER function using the N20.1 mouse oligodendroglial cell line to evaluate the response of ERalpha and ERbeta to estradiol (E2), a raloxifene analog LY117018 (LY) and 4-hydroxytamoxifen (4OHT).

DESIGN: We tested the ability of exogenous ER to activate transcription in response to ligands (100 nM) using the glial cell line N20.1 in a transient cotransfection assay with an ERalpha or ERbeta expression vector, an ERE-driven reporter and a Renilla luciferase transfection control.

RESULTS: Endogenous ER was not detected in the N20.1 cells by Western immunoblotting. E2 stimulated both ERalpha and ERbeta on both ERE- and AP-1 driven promoters. The transcription stimulation by E2 in the ERalpha and ERbeta through the AP-1driven promoter, though significant, was not of the same magnitude as the stimulation of the ERalpha through the ERE-driven promoter. 4OHT and LY did not show significant transcriptional activation of either the ERalpha or ERbeta, through either the ERE or AP-1 driven promoters. LY, at a 10-fold higher concentration than E2, showed a difference in its antagonist activity on the ERbeta through the AP-1 pathway when compared with the ERE- driven promoter, demonstrating not only promoter specificity, but also receptor specificity.

CONCLUSIONS: This is the first description of the activity of 4OHT and LY on estrogen receptors in glia....

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Journal Article 2005; 26(5): 541-547 PubMed PMID: 16264403 Citation  Keywords:  Aging:metabolism, Animals, Brain Chemistry:physiology, Digoxigenin, In Situ Hybridization, Liver:metabolism, Male, Mice, Mice, Inbred C57BL, RNA Probes, RNA, Complementary:biosynthesis, RNA, Messenger:analysis, Receptors, Cytoplasmic and Nuclear:biosynthe.   

OBJECTIVES: The distribution of Liver receptor homolog 1 (LRH-1) mRNA was studied in mice brain with the aim to establish whether this nuclear hormone receptor is expressed also in the brain in addition to liver and classical steroidogenic tissues.

METHODS: Expression of LRH-1 mRNA in juvenile (30 days old) and adult (60 days old) mouse brain was examined using non-radioactive in situ hybridization with digoxigenin labeled cRNA probes and with RT PCR using specific primers.

RESULTS: LRH-1 was strongly expressed throughout the brain. Semiquantitative RT PCR revealed very strong expression of LRH-1 mRNA in cerebrum in comparison to liver and testis, and in situ hybridization revealed that LRH-1 mRNA is uniformly expressed in most brain areas.

CONCLUSIONS: LRH-1 is strongly expressed throughout the mouse brain suggesting important roles for this transcription factor, although its precise roles in the CNS remain to be elucidated....

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Journal Article 2005; 26(4): 367-372 PubMed PMID: 16136007 Citation  Keywords:  Animals, Hypothalamo-Hypophyseal System:metabolism, In Vitro Techniques, Male, Neurokinin A:analogs & derivatives, Neurokinin-1 Receptor Antagonists, Neurotransmitter Agents:pharmacology, Peptide Fragments:pharmacology, Rats, Rats, Wistar, Receptors, Neur.   

OBJECTIVES: Present experiments were undertaken to study the influence of peptide NK-1 and NK-2 receptor agonists and antagonists as well as substance P and neurokinin A (the natural ligands for these tachykinin receptors) on vasopressin (AVP) secretion from the rat hypothalamo-neurohypophysial (HN) system in vitro.

RESULTS: The results showed that both substance P and highly selective tachykinin NK-1 receptor agonist, i.e., [Sar9,Met(O2)11]-Substance P, enhanced significantly AVP secretion, while the NK-1 receptor antagonist (Tyr6,D-Phe7,D-His9)-Substance P (6-11)--sendide--was found to antagonize the substance P-induced hormone release from isolated rat HN system (all peptides at the concentration of 10(-7) M/L). The NK-2 receptor selective agonist (beta-Ala8)-Neurokinin A (4-10) was essentially inactive in modifying AVP release from the rat HN system in vitro, while neurokinin A (the natural ligand for this tachykinin receptor) was found to stimulate the AVP release; this effect of neurokinin A has been diminished by the NK-2 receptor antagonist (Tyr5,D-Trp(6,8,9),Lys-NH2(10))-Neurokinin A (4-10).

CONCLUSION: The present data indicate a role for tachykinin NK-1 (and possibly for NK-2) receptors in tachykinin-mediated stimulation of AVP secretion from the rat HN system in vitro....

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