This study investigated the effects of microglia-derived brain-derived neurotrophic factor (BDNF) on social behaviors and medial prefrontal cortex (mPFC) development in mice. Social isolation during the juvenile period (p21-p35) increased BDNF in microglia and reduced adult sociability. Transgenic mice overexpressing microglial BDNF showed impaired sociability and excessive mPFC inhibitory neuronal circuit activity. Normalizing BDNF from p21 restored sociability and mPFC function, but normalization from p45-p60 did not fully normalize mPFC excitatory/inhibitory dynamics. Human data showed a positive correlation between adverse childhood experiences and BDNF expression in macrophages, suggesting a translational link between microglial BDNF and childhood experiences.

Takashi Komori, Kazuya Okamura, Inhibou Ikehara, Kazuhiko Yamamuro, Nozomi Endo, Kazuki Okumura, Takahira Yamauchi, Daisuke Ikawa, Noriko Ouji-Sageshima, Michihiro Toritsuka, Ryohei Takada, Yoshinori Kayashima, Rio Ishida, Yuki Mori, Kohei Kanemkawa, Yuki Noriyama, Yuki Nishi, Toshihiro Ito, Yasuhiko Saito, Mayumi Nishi, Toshifumi Kishimoto, Fumiaki Tanaka, Noboru Hori, Manabu Makino