Astroglial excitability and gliotransmission: an appraisal of Ca2+ as a signalling route

Astroglial cells, due to their passive electrical properties, were long considered subservient to neurons and to merely provide the framework and metabolic support of the brain. Although astrocytes do play such structural and housekeeping roles in the brain, these glial cells also contribute to the brain's computational power and behavioural output. These more active functions are endowed by the Ca2+-based excitability displayed by astrocytes. An increase in cytosolic Ca2+ levels in astrocytes can lead to the release of signalling molecules, a process termed gliotransmission, via the process of regulated exocytosis. Dynamic components of astrocytic exocytosis include the vesicular-plasma membrane secretory machinery, as well as the vesicular traffic, which is governed not only by general cytoskeletal elements but also by astrocyte-specific IFs (intermediate filaments). Gliotransmitters released into the ECS (extracellular space) can exert their actions on neighbouring neurons, to modulate synaptic transmission and plasticity, and to affect behaviour by modulating the sleep homoeostat. Besides these novel physiological roles, astrocytic Ca2+ dynamics, Ca2+-dependent gliotransmission and astrocyte–neuron signalling have been also implicated in brain disorders, such as epilepsy. The aim of this review is to highlight the newer findings concerning Ca2+ signalling in astrocytes and exocytotic gliotransmission. For this we report on Ca2+ sources and sinks that are necessary and sufficient for regulating the exocytotic release of gliotransmitters and discuss secretory machinery, secretory vesicles and vesicle mobility regulation. Finally, we consider the exocytotic gliotransmission in the modulation of synaptic transmission and plasticity, as well as the astrocytic contribution to sleep behaviour and epilepsy

Slow GABA transient and receptor desensitization shape synaptic responses evoked by hippocampal neurogliaform cells.

The kinetics of GABAergic synaptic currents can vary by an order of magnitude depending on the cell type. The neurogliaform cell (NGFC) has recently been identified as a key generator of slow GABA(A) receptor-mediated volume transmission in the isocortex. However, the mechanisms underlying slow GABA(A) receptor-mediated IPSCs and their use-dependent plasticity remain unknown. Here, we provide experimental and modeling data showing that hippocampal NGFCs generate an unusually prolonged (tens of milliseconds) but low-concentration (micromolar range) GABA transient, which is responsible for the slow response kinetics and which leads to a robust desensitization of postsynaptic GABA(A) receptors. This strongly contributes to the use-dependent synaptic depression elicited by various patterns of NGFC activity including the one detected during theta network oscillations in vivo. Synaptic depression mediated by NGFCs is likely to play an important modulatory role in the feedforward inhibition of CA1 pyramidal cells provided by the entorhinal cortex

Ectopic pregnancy in women with recurrent miscarriage

The aim of this study was to investigate the possible association between recurrent miscarriage (RM) and ectopic pregnancy (EP)

OLR1 and Loxin Expression in PBMCs of Women with a History of Unexplained Recurrent Miscarriage: A Pilot Study

The aim of this study was to evaluate the expression of OLR1 and its alternative splicing isoform Loxin in unexplained recurrent miscarriage (uRM)

Amniotic fluid antiphospholipid antibodies: Potential role in antiphospholipid syndrome-independent aberrant implantation process

Background The direct role of antiphospholipid antibodies (aPL) at maternal-fetal interface has not been fully investigated, especially whether they are involved in physiological and pathological implantation conditions, in an antiphospholipid syndrome (APS)-independent manner. In fact, trophoblast cells and placental endothelial cells at the implantation site express potential aPL targeted-phospholipid antigens (PL Ags); thus, the local production and presence of their specific antibodies, not related to APS (characterized by aPL presence in the peripheral blood), could be a potential marker of aberrant invasion, implantation and fetal-maternal immune tolerance processes. Methods Anti-Beta(2)glycoprotein I (anti-beta(2)GPI) and anticardiolipin (aCL Ab) antibodies (the most clinically relevant aPL) were detected by immunoenzymatic assay (ELISA), in the amniotic fluid (AF) of 167 women with physiological and complicated common pregnancy conditions, sharing an aberrant implantation process, such as recurrent pregnancy loss (RPL), autoimmune hypothyroidism (ahT) and smoking. All women included in the study were negative to peripheral blood aPL. Results aCL and anti-beta(2)GPI antibodies were detectable in all the AF samples. RPL, ahT and smoking patients had higher level of anti-beta(2)GPI Abs (IgM) compared to women with physiological pregnancies (p < 0.0001). Since IgM cannot cross the placenta, their local production in response to maternal-fetal interface stimuli, could be hypothesized. Conclusions The presence of aPL in the AF (not related to APS) could reveal a potential clinical significance at maternal-fetal interface in selected pregnancy complications, in which an aberrant implantation process, and in turn an impaired fetal-maternal immune tolerance cross-talk, could occur

Three-hour analysis of non-invasive foetal sex determination: application of Plexor chemistry

Contesto: La conoscenza del singolo "status" genetico in epoca prenatale è particolarmente rilevante nel caso di storia familiare positiva per le malattie genetiche, in età materna avanzata e in screening generale per anomalie fetali. In questo contesto, qui, riportiamo un saggio molecolare innovativo che utilizza il DNA fetale acellulare (cffDNA) come fonte per la diagnosi precoce e rapida del sesso fetale. Lo studio ha coinvolto 132 donne in gravidanza nei primi 3 mesi di gravidanza, che hanno accettato di dare un campione di sangue. Tutti i campioni raccolti sono stati immediatamente sottoposti alla separazione del plasma, che è stato utilizzato per l'estrazione del cffDNA. Successivamente, il cffDNA estratto è stato analizzato con un metodo PCR quantitativo (qPCR) basato su Plexor-HY chimico, che è in grado di identificare simultaneamente, quantificare e discriminare il DNA autosomico dal DNA legato al sesso. Risultati: In generale, il dosaggio Plexor-HY ha dimostrato di essere sensibile e specifico per la determinazione del DNA lowtemplate, come il cffDNA. Infatti, il saggio Plexor-HY è stato eseguito con successo in tutti i campioni, identificando 70 maschi e 62 femmine. Come il sesso fetale può essere fornito in 120 min solo utilizzando un campione di sangue materno come sorgente cffDNA, il saggio rappresenta un metodo prenatale molto veloce, sicuro e non invasivo. Conclusioni: La possibilità di determinare il sesso del feto nella vita prenatale precoce consente la applicazione del nostro test come test di screening utile per i soggetti e le famiglie a rischio di patologie legate al sesso. Inoltre, la conoscenza anticipata del sesso del feto può essere di grande aiuto anche per lo specialista, che potrebbe prontamente consigliare i pazienti sui rischi fetali di ereditare disturbi legati al sesso e l'utilità clinica di eseguire una diagnosi prenatale invasiva.Background: The knowledge of the individual genetic “status” in the prenatal era is particularly relevant in the case of positive family history for genetic diseases, in advanced maternal age and in the general screening for foetal abnormalities. In this context, here, we report an innovative molecular assay which utilizes the cell-free foetal DNA (cffDNA) as a source for the early and fast detection of the foetal sex. The study involved 132 pregnant women in their first 3 months of pregnancy, who agreed to give a blood sample. All the collected samples were immediately subjected to the separation of the plasma, which was utilized for the extraction of the cffDNA. Successively, the extracted cffDNA was analysed by a quantitative PCR (qPCR) method based on Plexor-HY chemistry, which is able to simultaneously identify, quantify and discriminate the autosomal DNA from the sex-linked DNA. Results: Overall, the Plexor-HY assay demonstrated to be sensitive and specific for the determination of lowtemplate DNA, such as the cffDNA. In fact, the Plexor-HY assay has been successfully performed in all the samples, identifying 70 males and 62 females. As the foetal sex can be provided in 120 min just by utilizing a maternal blood sample as cffDNA source, the assay represents a very fast, safe and non-invasive prenatal method. Conclusions: The possibility of determining the foetal sex in the early prenatal life consents the application of our assay as a helpful screening test for subjects and families at risk of sex-linked disorders. Moreover, the early knowledge of the foetal sex may be of great help even for the specialist, who might promptly advise the patients concerning the foetal risk of inheriting sex-linked disorders and the clinical utility of performing an invasive prenatal diagnosis