Glutamate (Glu), the major excitatory neurotransmitter, elicits its action through the activation of membrane receptors and transporters expressed in neurons and glial cells. Glial glutamate transporters, EAAT1 and EAAT2, remove this transmitter from the synaptic cleft preventing an excitotoxic insult. The Notch pathway is a signaling system involved in neuro- and gliogenesis. Radial glia (RG) generates neurons, oligodendrocytes, and astrocytes in a spatial and temporal pattern, in which Notch represses neurogenesis, maintaining the self-renewal potential of RG. Astrogenesis depends on several stimuli, Notch being a master regulator of the differentiation process. The cAMP-PKA-CREB signaling cascade cross talks with the Notch pathway, acting synergistically by reducing progenitor markers and inducing astrocytic differentiation. Notch1 mRNA is upregulated in a PKA/γ-secretase/NICD/CSL-dependent manner, suggesting a feedback loop to keep Notch active until astrocytic differentiation is complete. Glial differentiation is also modulated by PKC, which acts over NICD. In RG cells and astrocytes enwrapping glutamatergic synapses, EAAT1 transcriptional regulation is mediated by PKC, increasing Notch expression and its receptor intracellular traffic. It is clear that Notch represents an activity-dependent molecular key in RG cells that enable them to shape glutamatergic transmission through the expression of genes involved in glial/neuronal interactions.
Part of the book: GABA And Glutamate
In the field of assisted reproductive technology, endometrial receptivity is a crucial aspect that affects implantation rates in in-vitro fertilization procedures; in fact, impaired endometrial receptivity has been identified as the rate-limiting step for favorable pregnancy outcomes once factors regarding embryo quality have been optimized. The endometrium is a dynamic tissue that undergoes proliferative and secretory changes in each menstrual cycle, acquiring a short and transient period of embryo receptivity known as the Window of Implantation. Precise embryo-endometrial synchrony is necessary to achieve a successful pregnancy, and it involves complex and multifactorial processes related to morphological, biochemical, and genetic changes. On that behalf, defining the receptive window of each patient for personalized embryo transfer is a current goal. Here, we review different indicators of endometrial receptivity throughout the menstrual cycle, spotlighting the opening of the window of implantation: classical histological and biochemical markers, genetic factors, leading-edge transcriptomic signatures and miRNA profiles, and novel features such as the microbiome and secretome. Understanding the molecular mechanisms behind endometrial receptivity will facilitate the optimization and improvement of infertility treatments.
Part of the book: Modern Medical Genetics and Genomics