| Journal Title /掲載ジャーナル名 |
Biology of Sex Differences |
| Publication Year and Month /掲載年月 |
December, 2025 |
| Paper Title /論文タイトル |
Sex-related upregulation of bone morphogenetic protein signaling inhibits adult neurogenesis in APP NL-G-F alzheimer’s disease model mice |
| DOI /論文DOI |
10.1186/s13293-025-00799-0 |
| Author of Waseda University /本学の著者 |
OHSHIMA, Toshio(Professor, Faculty of Science and Engineering, Graduate School of Advanced Science and Engineering):Correspoinding Author |
| Related Websites /関連Web |
– |
| Abstract /抄録 |
BackgroundBone morphogenetic proteins (BMPs) have been reported in many studies to be related to adult neurogenesis. Neurogenic impairment is a hallmark of Alzheimer’s disease (AD), while the involvement of BMPs remains unclear. MethodsAD models were established using APPNL−G−F transgenic mice and C57BL/6 mice subjected to intracerebral injection of Aβ(25–35) peptide. Female APPNL−G−F mice received pharmacological inhibitor treatment, whereas Neuro2a cells were exposed to estrogen stimulation in vitro. Immunofluorescence staining was conducted to evaluate hippocampal neural stem cell proliferation. The hippocampus and cellular pellets were isolated, and quantitative PCR (qPCR) was employed to determine mRNA expression levels. ResultsOur study revealed that APPNL−G−F mice and Aβ-injected mice exhibited impaired neurogenesis in the brain, with a clear sex-dependent difference only in APP mice. Several BMPs were markedly upregulated in the hippocampus of AD model mice, with significantly higher expression in females than in males. BMP inhibitor attenuated neural stem cell proliferation deficits in female APPNL−G−F mice. Estrogen stimulation robustly enhanced BMP6 expression in Neuro2a cells. ConclusionsOur findings reveal a sex-dependent impairment of neurogenesis in APPNL−G−F mice driven by BMP signaling. Blocking BMP signaling enhances adult neural stem cell proliferation in female APPNL−G−F mice, providing a potential therapeutic target for AD. |
