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      Developmental dynamics of neurotensin binding sites in the human hypothalamus during the first postnatal year

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          Abstract

          The aim of the present study was to determine a detailed mapping of neurotensin (NT) in the human hypothalamus, during the first postnatal year using an in vitro quantitative autoradiography technique and the selective radioligand monoiodo-Tyr3-NT. Ten human postmortem hypothalami obtained from control neonates and infants (aged from 2 h to 1 year of postnatal age) were used. The biochemical kinetics of the binding in all obtained in this study revealed that the binding affinity constants were of high affinity (in the nanomolar range) and did not differ significantly between all cases investigated. Furthermore, competition experiments show insensitivity to levocabastine and were in favor of the presence of the high affinity site of NT receptor. Autoradiographic distribution showed that NT binding sites were widely distributed throughout the rostrocaudal extent of the hypothalamus. However, the distribution of NT binding sites was not homogenous and regional variations exist. In general, the highest densities were mainly present in the anterior hypothalamic level, particularly in the preoptic area. High NT binding site densities are also present at the mediobasal hypothalamic level, particularly in the paraventricular, parafornical, and dorsomedial nuclei. At the posterior level, low to very low densities could be observed in all the mammillary complex subdivisions, as well as the posterior hypothalamic area. Although this topographical distribution is almost identical during the postnatal period analyzed, age-related variations exist in discrete structures of the hypothalamus. The densities were higher in neonates/less aged infants than older infants in preoptic area (medial and lateral parts). The developmental profile is characterized by a progressive decrease from the neonate period to 1 year of postnatal age with a tendency to reach adult levels. On the other hand, the low levels of NT binding sites observed in posterior hypothalamus did not vary during the first postnatal year. They contrast in that with the very high levels we reported previously in adult. In conclusion, the present study demonstrates the occurrence of high NT binding sites density in various structures in many regions in the human neonate/infant hypothalamus, involved in the control of neuroendocrine and/or neurovegetative functions.

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          Neurotensin and neurotensin receptors.

          Neurotensin is a brain and gastrointestinal peptide that fulfils many central and peripheral functions through its interaction with specific receptors. Three subtypes of neurotensin receptors have been cloned. Two of them belong to the family of G protein-coupled receptors, whereas the third one is an entirely new type of neuropeptide receptor and is identical to gp95/sortilin, a 100 kDa-protein with a single transmembrane domain. In this review, the present knowledge regarding the molecular and pharmacological properties of the three cloned neurotensin receptors is summarized and the relationship between these receptors and the known pharmacological effects of neurotensin is discussed.
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            Development of projection neuron types, axon pathways, and patterned connections of the mammalian cortex.

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              Involvement of the neurotensin receptor-3 in the neurotensin-induced migration of human microglia.

              Microglia motility plays a crucial role in response to lesion or exocytotoxic damage of the cerebral tissue. We used two in vitro assays, a wound-healing model and a chemotaxis assay, to show that the neuropeptide neurotensin elicited the migration of the human microglial cell line C13NJ by a mechanism dependent on both phosphatidylinositol 3-kinase (PI 3-kinase) and mitogen-activated protein (MAP) kinase pathways. The effect of neurotensin on cell migration was blocked by the neurotensin receptor-3 propeptide, a selective ligand of this receptor. We demonstrate, by using RT-PCR, photoaffinity labeling, and Western blot analysis, that the type I neurotensin receptor-3 was the only known neurotensin receptor expressed in these microglial cells and that its activation led to the phosphorylation of both extracellular signal-regulating kinases 1/2 and Akt. Furthermore, the effect of neurotensin on cell migration was preceded by a profound modification of the F-actin cytoskeleton, particularly by the rapid formation of numerous cell filopodia. Both the motility and the filopodia appearance induced by neurotensin were totally blocked by selective inhibitors of MAP kinases or PI 3-kinase pathways. This demonstrates that the neurotensin receptor-3 is functional and mediates the migratory actions of neurotensin.
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                Author and article information

                Contributors
                Journal
                Front Cell Neurosci
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Media S.A.
                1662-5102
                10 September 2014
                2014
                : 8
                : 251
                Affiliations
                [1] 1Biological Engineering Laboratory, Life Sciences, Sultan Moulay Slimane University Beni-Mellal, Morocco
                [2] 2Unité de Formation et de Recherche de Biologie, Université de Bordeaux 1, Talence France
                [3] 3Lyon 1 University Lyon, France
                Author notes

                Edited by: Marie Z. Moftah, Alexandria University, Egypt

                Reviewed by: Youssef Aboussaleh, Ibn Tofail University, Morocco; Valérie Compan, Universit de Nmes, France

                *Correspondence: Mohamed Najimi, Biological Engineering Laboratory, Life Sciences, Sultan Moulay slimane University, P. O. Box 523, Beni-Mellal 23000, Morocco e-mail: mnajimi1@ 123456fstbm.ac.ma

                This article was submitted to the journal Frontiers in Cellular Neuroscience.

                Article
                10.3389/fncel.2014.00251
                4160091
                53189411-1db2-48e3-b23b-3ec32494140a
                Copyright © 2014 Najimi, Sarrieau, Kopp and Chigr.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 April 2014
                : 07 August 2014
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 61, Pages: 9, Words: 0
                Categories
                Neuroscience
                Original Research Article

                Neurosciences
                neurotensin receptor,human hypothalamus,newborn brain,infant brain development,autoradiography

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