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2h ago

Fluoxetine Rewires Prefrontal Interneurons’ Gene Programs, Easing Circuit Constraints

Peer-reviewed work from Finnish teams maps cell-specific transcriptomic changes alongside structural signs consistent with a more adaptable cortical state.

Using cell type–specific transcriptome profiling, researchers found that after two weeks of treatment, a special class of brain cells, called parvalbumin interneurons, which help keep brain activity balanced, became less rigid in the prefrontal cortex. Credit: Neuroscience News

Overview

  • After two weeks of treatment, parvalbumin interneurons in the prefrontal cortex showed reduced expression of mitochondrial ATP-production and ribosomal pathways with increased expression of plasticity-related genes.
  • Immunohistochemistry revealed weakened perineuronal nets and lower PV signal in select prefrontal subregions, a signature associated with greater circuit flexibility.
  • FACS-sorted PV+ cells displayed higher mitochondrial DNA levels with unchanged intracellular ATP, and TOMM22 intensity rose slightly in the prelimbic region, suggesting compensatory mitochondrial responses.
  • TRAP, FACS, and histology identified roughly 50 altered pathways, including upregulation linked to phosphatase activity, ion channels, and cytoskeletal remodeling.
  • The study, led by researchers at the University of Eastern Finland and the University of Helsinki and published in Neuropsychopharmacology, remains preclinical with causal links to therapeutic outcomes yet to be established.