Cargando…

Kif21B mediates the effect of estradiol on the morphological plasticity of mouse hippocampal neurons

INTRODUCTION: Neurons are polarized cells, and their ability to change their morphology has a functional implication in the development and plasticity of the nervous system in order to establish new connections. Extracellular factors strongly influence neuronal shape and connectivity. For instance,...

Descripción completa

Detalles Bibliográficos
Autores principales: Ganchala, Danny, Pinto-Benito, Daniel, Baides, Elisa, Ruiz-Palmero, Isabel, Grassi, Daniela, Arevalo, Maria Angeles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10106616/
https://www.ncbi.nlm.nih.gov/pubmed/37078090
http://dx.doi.org/10.3389/fnmol.2023.1143024
_version_ 1785026441775153152
author Ganchala, Danny
Pinto-Benito, Daniel
Baides, Elisa
Ruiz-Palmero, Isabel
Grassi, Daniela
Arevalo, Maria Angeles
author_facet Ganchala, Danny
Pinto-Benito, Daniel
Baides, Elisa
Ruiz-Palmero, Isabel
Grassi, Daniela
Arevalo, Maria Angeles
author_sort Ganchala, Danny
collection PubMed
description INTRODUCTION: Neurons are polarized cells, and their ability to change their morphology has a functional implication in the development and plasticity of the nervous system in order to establish new connections. Extracellular factors strongly influence neuronal shape and connectivity. For instance, the developmental actions of estradiol on hippocampal neurons are well characterized, and we have demonstrated in previous studies that Ngn3 mediates these actions. On the other hand, Kif21B regulates microtubule dynamics and carries out retrograde transport of the TrkB/brain-derived neurotrophic factor (BDNF) complex, essential for neuronal development. METHODS: In the present study, we assessed the involvement of kinesin Kif21B in the estradiol-dependent signaling mechanisms to regulate neuritogenesis through cultured mouse hippocampal neurons. RESULTS: We show that estradiol treatment increases BDNF expression, and estradiol and BDNF modify neuron morphology through TrkB signaling. Treatment with K252a, a TrkB inhibitor, decreases dendrite branching without affecting axonal length, whereas. Combined with estradiol or BDNF, it blocks their effects on axons but not dendrites. Notably, the downregulation of Kif21B abolishes the actions of estradiol and BDNF in both the axon and dendrites. In addition, Kif21B silencing also decreases Ngn3 expression, and downregulation of Ngn3 blocks the effect of BDNF on neuron morphology. DISCUSSION: These results suggest that Kif21B is required for the effects of estradiol and BDNF on neuronal morphology, but phosphorylation-mediated activation of TrkB is essential only for axonal growth. Our results show that the Estradiol/BDNF/TrkB/Kif21B/Ngn3 is a new and essential pathway mediating hippocampal neuron development.
format Online
Article
Text
id pubmed-10106616
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-101066162023-04-18 Kif21B mediates the effect of estradiol on the morphological plasticity of mouse hippocampal neurons Ganchala, Danny Pinto-Benito, Daniel Baides, Elisa Ruiz-Palmero, Isabel Grassi, Daniela Arevalo, Maria Angeles Front Mol Neurosci Molecular Neuroscience INTRODUCTION: Neurons are polarized cells, and their ability to change their morphology has a functional implication in the development and plasticity of the nervous system in order to establish new connections. Extracellular factors strongly influence neuronal shape and connectivity. For instance, the developmental actions of estradiol on hippocampal neurons are well characterized, and we have demonstrated in previous studies that Ngn3 mediates these actions. On the other hand, Kif21B regulates microtubule dynamics and carries out retrograde transport of the TrkB/brain-derived neurotrophic factor (BDNF) complex, essential for neuronal development. METHODS: In the present study, we assessed the involvement of kinesin Kif21B in the estradiol-dependent signaling mechanisms to regulate neuritogenesis through cultured mouse hippocampal neurons. RESULTS: We show that estradiol treatment increases BDNF expression, and estradiol and BDNF modify neuron morphology through TrkB signaling. Treatment with K252a, a TrkB inhibitor, decreases dendrite branching without affecting axonal length, whereas. Combined with estradiol or BDNF, it blocks their effects on axons but not dendrites. Notably, the downregulation of Kif21B abolishes the actions of estradiol and BDNF in both the axon and dendrites. In addition, Kif21B silencing also decreases Ngn3 expression, and downregulation of Ngn3 blocks the effect of BDNF on neuron morphology. DISCUSSION: These results suggest that Kif21B is required for the effects of estradiol and BDNF on neuronal morphology, but phosphorylation-mediated activation of TrkB is essential only for axonal growth. Our results show that the Estradiol/BDNF/TrkB/Kif21B/Ngn3 is a new and essential pathway mediating hippocampal neuron development. Frontiers Media S.A. 2023-04-03 /pmc/articles/PMC10106616/ /pubmed/37078090 http://dx.doi.org/10.3389/fnmol.2023.1143024 Text en Copyright © 2023 Ganchala, Pinto-Benito, Baides, Ruiz-Palmero, Grassi and Arevalo. https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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.
spellingShingle Molecular Neuroscience
Ganchala, Danny
Pinto-Benito, Daniel
Baides, Elisa
Ruiz-Palmero, Isabel
Grassi, Daniela
Arevalo, Maria Angeles
Kif21B mediates the effect of estradiol on the morphological plasticity of mouse hippocampal neurons
title Kif21B mediates the effect of estradiol on the morphological plasticity of mouse hippocampal neurons
title_full Kif21B mediates the effect of estradiol on the morphological plasticity of mouse hippocampal neurons
title_fullStr Kif21B mediates the effect of estradiol on the morphological plasticity of mouse hippocampal neurons
title_full_unstemmed Kif21B mediates the effect of estradiol on the morphological plasticity of mouse hippocampal neurons
title_short Kif21B mediates the effect of estradiol on the morphological plasticity of mouse hippocampal neurons
title_sort kif21b mediates the effect of estradiol on the morphological plasticity of mouse hippocampal neurons
topic Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10106616/
https://www.ncbi.nlm.nih.gov/pubmed/37078090
http://dx.doi.org/10.3389/fnmol.2023.1143024
work_keys_str_mv AT ganchaladanny kif21bmediatestheeffectofestradiolonthemorphologicalplasticityofmousehippocampalneurons
AT pintobenitodaniel kif21bmediatestheeffectofestradiolonthemorphologicalplasticityofmousehippocampalneurons
AT baideselisa kif21bmediatestheeffectofestradiolonthemorphologicalplasticityofmousehippocampalneurons
AT ruizpalmeroisabel kif21bmediatestheeffectofestradiolonthemorphologicalplasticityofmousehippocampalneurons
AT grassidaniela kif21bmediatestheeffectofestradiolonthemorphologicalplasticityofmousehippocampalneurons
AT arevalomariaangeles kif21bmediatestheeffectofestradiolonthemorphologicalplasticityofmousehippocampalneurons