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Perineuronal Net Formation during the Critical Period for Neuronal Maturation in the Hypothalamic Arcuate Nucleus

In leptin-deficient ob/ob mice, obesity and diabetes are associated with abnormal development of neurocircuits in the hypothalamic arcuate nucleus (ARC)(1), a critical brain area for energy and glucose homeostasis(2,3). As this developmental defect can be remedied by systemic leptin administration,...

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Autores principales: Mirzadeh, Zaman, Alonge, Kimberly M., Cabrales, Elaine, Herranz-Pérez, Vicente, Scarlett, Jarrad M., Brown, Jenny M., Hassouna, Rim, Matsen, Miles E., Nguyen, Hong T., Garcia-Verdugo, Jose Manuel, Zeltser, Lori M., Schwartz, Michael W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594569/
https://www.ncbi.nlm.nih.gov/pubmed/31245789
http://dx.doi.org/10.1038/s42255-018-0029-0
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author Mirzadeh, Zaman
Alonge, Kimberly M.
Cabrales, Elaine
Herranz-Pérez, Vicente
Scarlett, Jarrad M.
Brown, Jenny M.
Hassouna, Rim
Matsen, Miles E.
Nguyen, Hong T.
Garcia-Verdugo, Jose Manuel
Zeltser, Lori M.
Schwartz, Michael W.
author_facet Mirzadeh, Zaman
Alonge, Kimberly M.
Cabrales, Elaine
Herranz-Pérez, Vicente
Scarlett, Jarrad M.
Brown, Jenny M.
Hassouna, Rim
Matsen, Miles E.
Nguyen, Hong T.
Garcia-Verdugo, Jose Manuel
Zeltser, Lori M.
Schwartz, Michael W.
author_sort Mirzadeh, Zaman
collection PubMed
description In leptin-deficient ob/ob mice, obesity and diabetes are associated with abnormal development of neurocircuits in the hypothalamic arcuate nucleus (ARC)(1), a critical brain area for energy and glucose homeostasis(2,3). As this developmental defect can be remedied by systemic leptin administration, but only if given before postnatal day 28, a critical period (CP) for leptin-dependent development of ARC neurocircuits has been proposed(4). In other brain areas, CP closure coincides with the appearance of perineuronal nets (PNNs), extracellular matrix specializations that restrict the plasticity of neurons that they enmesh(5). Here we report that in humans as well as rodents, subsets of neurons in the mediobasal aspect of the ARC are enmeshed by PNN-like structures. In mice, these neurons are densely-packed into a continuous ring that encircles the junction of the ARC and median eminence, which facilitates exposure of ARC neurons to the circulation. Most of the enmeshed neurons are both GABAergic and leptin receptor-positive, including a majority of Agrp neurons. Postnatal formation of the PNN-like structures coincides precisely with closure of the CP for Agrp neuron maturation and is dependent on input from circulating leptin, as postnatal ob/ob mice have reduced ARC PNN-like material that is restored by leptin administration during the CP. We conclude that neurons crucial to metabolic homeostasis are enmeshed by PNN-like structures and organized into a densely packed cluster situated circumferentially at the ARC-ME junction, where metabolically-relevant humoral signals are sensed.
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spelling pubmed-65945692019-07-21 Perineuronal Net Formation during the Critical Period for Neuronal Maturation in the Hypothalamic Arcuate Nucleus Mirzadeh, Zaman Alonge, Kimberly M. Cabrales, Elaine Herranz-Pérez, Vicente Scarlett, Jarrad M. Brown, Jenny M. Hassouna, Rim Matsen, Miles E. Nguyen, Hong T. Garcia-Verdugo, Jose Manuel Zeltser, Lori M. Schwartz, Michael W. Nat Metab Article In leptin-deficient ob/ob mice, obesity and diabetes are associated with abnormal development of neurocircuits in the hypothalamic arcuate nucleus (ARC)(1), a critical brain area for energy and glucose homeostasis(2,3). As this developmental defect can be remedied by systemic leptin administration, but only if given before postnatal day 28, a critical period (CP) for leptin-dependent development of ARC neurocircuits has been proposed(4). In other brain areas, CP closure coincides with the appearance of perineuronal nets (PNNs), extracellular matrix specializations that restrict the plasticity of neurons that they enmesh(5). Here we report that in humans as well as rodents, subsets of neurons in the mediobasal aspect of the ARC are enmeshed by PNN-like structures. In mice, these neurons are densely-packed into a continuous ring that encircles the junction of the ARC and median eminence, which facilitates exposure of ARC neurons to the circulation. Most of the enmeshed neurons are both GABAergic and leptin receptor-positive, including a majority of Agrp neurons. Postnatal formation of the PNN-like structures coincides precisely with closure of the CP for Agrp neuron maturation and is dependent on input from circulating leptin, as postnatal ob/ob mice have reduced ARC PNN-like material that is restored by leptin administration during the CP. We conclude that neurons crucial to metabolic homeostasis are enmeshed by PNN-like structures and organized into a densely packed cluster situated circumferentially at the ARC-ME junction, where metabolically-relevant humoral signals are sensed. 2019-01-21 2019-02 /pmc/articles/PMC6594569/ /pubmed/31245789 http://dx.doi.org/10.1038/s42255-018-0029-0 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Mirzadeh, Zaman
Alonge, Kimberly M.
Cabrales, Elaine
Herranz-Pérez, Vicente
Scarlett, Jarrad M.
Brown, Jenny M.
Hassouna, Rim
Matsen, Miles E.
Nguyen, Hong T.
Garcia-Verdugo, Jose Manuel
Zeltser, Lori M.
Schwartz, Michael W.
Perineuronal Net Formation during the Critical Period for Neuronal Maturation in the Hypothalamic Arcuate Nucleus
title Perineuronal Net Formation during the Critical Period for Neuronal Maturation in the Hypothalamic Arcuate Nucleus
title_full Perineuronal Net Formation during the Critical Period for Neuronal Maturation in the Hypothalamic Arcuate Nucleus
title_fullStr Perineuronal Net Formation during the Critical Period for Neuronal Maturation in the Hypothalamic Arcuate Nucleus
title_full_unstemmed Perineuronal Net Formation during the Critical Period for Neuronal Maturation in the Hypothalamic Arcuate Nucleus
title_short Perineuronal Net Formation during the Critical Period for Neuronal Maturation in the Hypothalamic Arcuate Nucleus
title_sort perineuronal net formation during the critical period for neuronal maturation in the hypothalamic arcuate nucleus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594569/
https://www.ncbi.nlm.nih.gov/pubmed/31245789
http://dx.doi.org/10.1038/s42255-018-0029-0
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