Placental CRH as a signal of pregnancy adversity and impact on fetal neurodevelopment

Early life is a period of considerable plasticity and vulnerability and insults during that period can disrupt the homeostatic equilibrium of the developing organism, resulting in adverse developmental programming and enhanced susceptibility to disease. Fetal exposure to prenatal stress can impede optimum brain development and deranged mother’s HPA axis stress responses can alter the neurodevelopmental trajectories of the offspring. Corticotropin-releasing hormone (CRH) and glucocorticoids, regulate fetal neurogenesis and while CRH exerts neuroprotective actions, increased levels of stress hormones have been associated with fetal brain structural alterations such as reduced cortical volume, impoverishment of neuronal density in the limbic brain areas and alterations in neuronal circuitry, synaptic plasticity, neurotransmission and GPCR signalling. Emerging evidence highlight the role of epigenetic changes in fetal brain programming, as stress-induced methylation of genes encoding molecules that are implicated in HPA axis and major neurodevelopmental processes. These serve as molecular memories and have been associated with long term modifications of the offspring’s stress regulatory system and increased susceptibility to psychosomatic disorders later in life. This review summarises our current understanding on the roles of CRH and other mediators of stress responses on fetal neurodevelopment

Η επίδραση της πλακουντιακής CRH στην ανάπτυξη του κεντρικού νευρικού συστήματος του εμβρύου υπό συνθήκες ενδομήτριου στρες

Η εμβρυική ζωή είναι μια περίοδος σημαντικής πλαστικότητας και οι προσβολές κατά τη διάρκεια αυτής, μπορούν να διαταράξουν την ομοιοστατική ισορροπία του αναπτυσσόμενου οργανισμού. Η έκθεση του εμβρύου σε προγεννητικό στρες μπορεί να εμποδίσει τη βέλτιστη ανάπτυξη του εγκεφάλου και να οδηγήσει σε διατάραξη του ιδεατού αναπτυξιακού προγραμματισμού και εμφάνιση ψυχοπαθολογίας στην ενήλικη ζωή. Οι διαταραγμένες αποκρίσεις του άξονα υποθαλάμου-υπόφυσης-επινεφριδίων (άξονας ΥΥΕ) της μητέρας υπό συνθήκες στρες, μπορούν να μεταβάλουν τις νευροαναπτυξιακές τροχιές των απογόνων. Η εκλυτική ορμόνη της κορτικοτροπίνης (CRH) και τα γλυκοκορτικοειδή, ρυθμίζουν την εμβρυϊκή νευρογένεση. Παρόλο που η CRH ασκεί νευροπροστατευτικές δράσεις στο νευρικό ιστό, τα αυξημένα επίπεδα των ορμονών του στρες, έχουν συσχετιστεί με δομικές μεταβολές του εμβρυϊκού εγκεφάλου όπως με μείωση του όγκου του φλοιού και της πυκνότητας των νευρώνων καθώς και με μεταβολές στα νευρωνικά κυκλώματα, στη συναπτική πλαστικότητα και νευροδιαβίβαση και στη σηματοδότηση υποδοχέων συνδεδεμένων με G-πρωτεΐνες (GPCRs). Νεότερα δεδομένα, αναδεικνύουν τον κρίσιμο ρόλο των, επαγόμενων από στρες, επιγενετικών αλλαγών στη νευροανάπτυξη του εμβρύου, με τη μεθυλίωση γονιδίων στόχων, που κωδικοποιούν μόρια τα οποία εμπλέκονται στον άξονα ΥΥΕ και σε σημαντικές νευροαναπτυξιακές διαδικασίες. Οι επιγενετικές αλλαγές αποτελούν ένα είδος κυτταρικής μνήμης και έχουν συσχετιστεί με μακροχρόνιες τροποποιήσεις του ρυθμιστικού συστήματος του στρες και με αυξημένη ευαισθησία των απογόνων σε ψυχοσωματικές διαταραχές. Η παρούσα βιβλιογραφική ανασκόπηση συνοψίζει τα υπάρχοντα ερευνητικά δεδομένα, σχετικά με τους ρόλους της CRH και των άλλων διαμεσολαβητών του στρες, στην εμβρυϊκή νευροανάπτυξη.Early life is a period of considerable plasticity and vulnerability and insults during that period can disrupt the homeostatic equilibrium of the developing organism, resulting in adverse developmental programming and enhanced susceptibility to disease. Fetal exposure to prenatal stress can impede optimum brain development and deranged mother’s hypothalamic–pituitary–adrenal axis (HPA axis) stress responses can alter the neurodevelopmental trajectories of the offspring. Corticotropin-releasing hormone (CRH) and glucocorticoids, regulate fetal neurogenesis and while CRH exerts neuroprotective actions, increased levels of stress hormones have been associated with fetal brain structural alterations such as reduced cortical volume, impoverishment of neuronal density in the limbic brain areas and alterations in neuronal circuitry, synaptic plasticity, neurotransmission and G-protein coupled receptor (GPCR) signalling. Emerging evidence highlight the role of epigenetic changes in fetal brain programming, as stress-induced methylation of genes encoding molecules that are implicated in HPA axis and major neurodevelopmental processes. These serve as molecular memories and have been associated with long term modifications of the offspring’s stress regulatory system and increased susceptibility to psychosomatic disorders later in life. This review summarises our current understanding on the roles of CRH and other mediators of stress responses on fetal neurodevelopment

Placental CRH as a Signal of Pregnancy Adversity and Impact on Fetal Neurodevelopment

Early life is a period of considerable plasticity and vulnerability and insults during that period can disrupt the homeostatic equilibrium of the developing organism, resulting in adverse developmental programming and enhanced susceptibility to disease. Fetal exposure to prenatal stress can impede optimum brain development and deranged mother's hypothalamic-pituitary-adrenal axis (HPA axis) stress responses can alter the neurodevelopmental trajectories of the offspring. Corticotropin-releasing hormone (CRH) and glucocorticoids, regulate fetal neurogenesis and while CRH exerts neuroprotective actions, increased levels of stress hormones have been associated with fetal brain structural alterations such as reduced cortical volume, impoverishment of neuronal density in the limbic brain areas and alterations in neuronal circuitry, synaptic plasticity, neurotransmission and G-protein coupled receptor (GPCR) signalling. Emerging evidence highlight the role of epigenetic changes in fetal brain programming, as stress-induced methylation of genes encoding molecules that are implicated in HPA axis and major neurodevelopmental processes. These serve as molecular memories and have been associated with long term modifications of the offspring's stress regulatory system and increased susceptibility to psychosomatic disorders later in life. This review summarises our current understanding on the roles of CRH and other mediators of stress responses on fetal neurodevelopment

Atypical Presentation of IgA Nephropathy Mimicking Acute Pyelonephritis

Background. IgA glomerulonephritis may present with hematuria, flank pain, and fever. This clinical presentation may be easily confused with acute pyelonephritis. Case Report. We present the case of a 25-year-old female with a typical clinical presentation for acute pyelonephritis (high fever, left flank pain, left costovertebral angle tenderness, hematuria, elevated inflammatory markers, and a hypoenhancing region in the left kidney on contrast-enhanced computed tomography). However, urine and blood cultures were both negative, the serum creatinine was elevated, and the urinalysis revealed significant proteinuria and dysmorphic red blood cells. A kidney biopsy confirmed a diagnosis of IgA nephropathy. She was treated with a combination of lisinopril and methylprednisolone, with good response. Conclusion. Gross hematuria, especially in the absence of pyuria or bacteriuria, should raise the suspicion for underlying IgA nephropathy, even if the rest of the clinical presentation is typical for a urinary tract infection. The presence of significant proteinuria, red blood cell casts, and dysmorphic red blood cells are useful clues suggesting glomerular disease

In-hospital screening for diabetes mellitus with HbA1c in an internal medicine department was not useful; a prospective pilot study

Background. Screening inpatients for diabetes mellitus may be a good opportunity to detect undiagnosed cases and several studies have demonstrated the feasibility and usefulness of this practice. HbA1c has been suggested as the method of choice due to the effects of acute illness on glucose. The aim of this study was to evaluate a screening protocol based on HbA1c to identify inpatients with undiagnosed diabetes mellitus in an internal medicine department