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Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior
Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors—associated with the medial prefrontal cortex (mPFC)—has a critical period during the juvenile perio...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350236/ https://www.ncbi.nlm.nih.gov/pubmed/37461488 http://dx.doi.org/10.21203/rs.3.rs-3094335/v1 |
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author | Makinodan, Manabu Komori, Takashi Okamura, Kazuya Ikehara, Minobu Yamamuro, Kazuhiko Endo, Nozomi Okumura, Kazuki Yamauchi, Takahira Ikawa, Daisuke Ouji-Sageshima, Noriko Toritsuka, Michihiro Takada, Ryohei Kayashima, Yoshinori Ishida, Rio Mori, Yuki Kamikawa, Kohei Noriyama, Yuki Nishi, Yuki Ito, T Saito, Yasuhiko Nishi, Mayumi Kishimoto, Toshifumi Tanaka, Kenji Hiroi, Noboru |
author_facet | Makinodan, Manabu Komori, Takashi Okamura, Kazuya Ikehara, Minobu Yamamuro, Kazuhiko Endo, Nozomi Okumura, Kazuki Yamauchi, Takahira Ikawa, Daisuke Ouji-Sageshima, Noriko Toritsuka, Michihiro Takada, Ryohei Kayashima, Yoshinori Ishida, Rio Mori, Yuki Kamikawa, Kohei Noriyama, Yuki Nishi, Yuki Ito, T Saito, Yasuhiko Nishi, Mayumi Kishimoto, Toshifumi Tanaka, Kenji Hiroi, Noboru |
author_sort | Makinodan, Manabu |
collection | PubMed |
description | Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors—associated with the medial prefrontal cortex (mPFC)—has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21–p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglia Bdnf—regulated using doxycycline at different time points—underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglia BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administration of doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological functions; this was not observed when BDNF was normalized from a later age (p45–p50). To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible substitute for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. Thus, microglia BDNF might regulate sociability and mPFC maturation in mice during the juvenile period. Furthermore, childhood experiences in humans may be related to BDNF secretion from macrophages. |
format | Online Article Text |
id | pubmed-10350236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-103502362023-07-17 Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior Makinodan, Manabu Komori, Takashi Okamura, Kazuya Ikehara, Minobu Yamamuro, Kazuhiko Endo, Nozomi Okumura, Kazuki Yamauchi, Takahira Ikawa, Daisuke Ouji-Sageshima, Noriko Toritsuka, Michihiro Takada, Ryohei Kayashima, Yoshinori Ishida, Rio Mori, Yuki Kamikawa, Kohei Noriyama, Yuki Nishi, Yuki Ito, T Saito, Yasuhiko Nishi, Mayumi Kishimoto, Toshifumi Tanaka, Kenji Hiroi, Noboru Res Sq Article Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors—associated with the medial prefrontal cortex (mPFC)—has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21–p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglia Bdnf—regulated using doxycycline at different time points—underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglia BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administration of doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological functions; this was not observed when BDNF was normalized from a later age (p45–p50). To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible substitute for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. Thus, microglia BDNF might regulate sociability and mPFC maturation in mice during the juvenile period. Furthermore, childhood experiences in humans may be related to BDNF secretion from macrophages. American Journal Experts 2023-06-30 /pmc/articles/PMC10350236/ /pubmed/37461488 http://dx.doi.org/10.21203/rs.3.rs-3094335/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Makinodan, Manabu Komori, Takashi Okamura, Kazuya Ikehara, Minobu Yamamuro, Kazuhiko Endo, Nozomi Okumura, Kazuki Yamauchi, Takahira Ikawa, Daisuke Ouji-Sageshima, Noriko Toritsuka, Michihiro Takada, Ryohei Kayashima, Yoshinori Ishida, Rio Mori, Yuki Kamikawa, Kohei Noriyama, Yuki Nishi, Yuki Ito, T Saito, Yasuhiko Nishi, Mayumi Kishimoto, Toshifumi Tanaka, Kenji Hiroi, Noboru Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior |
title | Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior |
title_full | Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior |
title_fullStr | Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior |
title_full_unstemmed | Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior |
title_short | Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior |
title_sort | brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350236/ https://www.ncbi.nlm.nih.gov/pubmed/37461488 http://dx.doi.org/10.21203/rs.3.rs-3094335/v1 |
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