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Previous study indicates that Kdm7a mRNA in the medial prefrontal cortex (mPFC) increases after drug exposure, yet its role in drug\u2010related behaviors is largely unknown. In a morphine\u2010conditioned place preference (CPP) paradigm, these findings reveal a specific increase of Kdm7a expression in the mPFC 7 days after drug withdrawal. Subsequently, these results demonstrate that knockdown of Kdm7a in the mPFC do not affect the acquisition of morphine\u2010induced CPP, but it attenuate memory consolidation. To further explore Kdm7a\u2010mediated transcriptomic changes, this work employs Nanopore direct RNA sequencing. Transcriptome profiling unveils several gene expression alterations impacted by KDM7A, which are enriched in relevant neural function categories. Notably, this work identifies and validates fascin actin\u2010bundling protein 1 (Fscn1) as a downstream molecular target. Knockdown of Fscn1 has a similar impact on CPP to Kdm7a, along with corresponding decrease of dendritic spine density and neuronal activity in the mPFC. Additionally, silencing Kdm7a decreases enrichment of H3K9me2 and H3K27me2 at the Fscn1 promoter region, suggesting that KDM7A may act as a crucial regulator of transcriptional responses to morphine\u2010related reward memory via Fscn1.<\/jats:p>","DOI":"10.1002\/advs.202405352","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T12:35:06Z","timestamp":1737462906000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Histone Lysine Demethylase KDM7A Contributes to Reward Memory via Fscn1\u2010Induced Synaptic Plasticity in the Medial Prefrontal Cortex"],"prefix":"10.1002","volume":"12","author":[{"given":"Zhuo\u2010jin","family":"Yang","sequence":"first","affiliation":[{"name":"College of Forensic Medicine Key Laboratory of National Health Commission for Forensic Medicine Xi'an Jiaotong University Health Science Center  Xi'an Shaanxi 710061 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