RESUMO
The growing body of evidence implicating tumor necrosis factor-α (TNFα) in the pathophysiology of psychiatric disorders led us to measure levels of that protein in the cortex of subjects with major depressive disorders (MDD). Having reported an increase (458%) in the levels of the transmembrane (tmTNFα), but not the soluble (sTNFα), form of the protein in Brodmann's area (BA) 46, but not 24, in people with the disorder, we decided to examine additional components of TNFα-related pathways in the same regions in people with MDD and extend our studies to the same cortical regions of people with schizophrenia (Sz) and bipolar disorders (BD). Using postmortem tissue, western blots and quantitative PCR, we have now shown there is a significant increase (305%) in tmTNFα in Brodmann's area 24, but not 46, from subjects with BD, and that levels of the protein were not altered in Sz. Levels of sTNFα were not altered in BD or Sz. In addition, we have shown that levels of TNF receptor 1 (TNFR1) mRNA are increased in BA 24 (53%) and BA 46 (82%) in people with Sz, whereas levels of TNFR2 mRNA was decreased in BA 46 in people with mood disorders (MDD=-51%; BD=-67%). Levels of proteins frequently used as surrogate markers of neuronal, astrocytic and microglia numbers, as well as levels of the pro-inflammatory marker (interleukin 1ß), were not changed in the cortex of people with mood disorders. Our data suggest there are differential changes in TNFα-related markers in the cortex of people with MDD, BD and Sz that may not be related to classical inflammation and may cause changes in different TNFα-related signaling pathways.
Assuntos
Transtorno Bipolar/metabolismo , Córtex Cerebral/metabolismo , Transtorno Depressivo Maior/metabolismo , Esquizofrenia/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-1beta/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Receptores Tipo II do Fator de Necrose Tumoral/metabolismoRESUMO
Ghrelin acting via the growth hormone secretagogue receptor (GHS-R) stimulates GH secretion from pituitary glands. Both ligand and receptor are present in the pituitary, hypothalamus and many peripheral tissues including the uterus. This study demonstrates the cyclical expression of GHS-R and ghrelin in human endometrium. mRNA and protein for ghrelin and GHS-R were examined using RT-PCR and immunohistochemistry. Both ghrelin and GHS-R mRNA levels were highest in the secretory phase, with lower levels in the mid-proliferative phase and even lower expression in the menstrual phase. Immunoreactive ghrelin and GHS-R were confined predominantly to glandular epithelial and stromal cells with the greatest intensity of staining in secretory phase samples, consistent with the RT-PCR data. Additionally, we examined ghrelins effect on the decidualization of human endometrial stromal cells (HESCs) combined with sex steroid and cAMP treatments using prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP-1) production as markers of decidualization. Ghrelin administered in combination with sex steroids to HESC, resulted in an increase in PRL and IGFBP-1 production above that obtained with cAMP, or sex steroids alone (P<0.001) whereas ghrelin in combination with cAMP inhibits the action of cAMP. These findings have potential clinical applications for the regulation of fertility.