BRIEF RESEARCH REPORT article
Front. Cell. Neurosci.
Sec. Cellular Neuropathology
Volume 19 - 2025 | doi: 10.3389/fncel.2025.1675003
Brain-derived neurotrophic factor prevents LPS-induced dysregulation of GABAergic interneuron markers in mouse hippocampus
Provisionally accepted
- 1Centre for Addiction and Mental Health, Toronto, Canada
- 2Department of Pharmacology, University of Toronto, Toronto, Canada
- 3Department of Pharmacology, and Department of Psychiatry, University of Toronto, Toronto, Canada
- 4Department of Psychiatry, University of Toronto, Toronto, Canada
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Inflammation causes reduced markers of GABAergic interneurons and brain-derived neurotrophic factor (BDNF) in the hippocampus, features often associated with neuropsychiatric disease pathophysiology. However, the mechanism connecting inflammation to GABAergic markers remains unclear. We hypothesized that reduced BDNF mediates the effects of lipopolysaccharide (LPS) on GABAergic markers and that hippocampal BDNF infusion would prevent LPS-induced reduction in somatostatin (SST), and coexpressed markers, including cortistatin (CORT), and neuropeptide Y (NPY). C57BL/6 mice (n = 14; 50% female) received intracerebral administration of BDNF (250 ng) or vehicle control in the hippocampus via stereotaxic surgery. Thirty minutes after BDNF administration, intraperitoneal injection of LPS (2 mg/kg) or phosphate buffered saline (PBS) was performed and mice were euthanized 18 hours post LPS-injection. The hippocampus was collected for investigation of cellular markers using quantitative PCR and enzyme-linked immunosorbent assay (ELISA). LPS administration in mice that did not receive pre-treatment with BDNF led to a significant reduction in mRNA levels of Bdnf (p = 0.0049), Sst (p = 0.0416), Npy (p = 0.0088), and Cort (p = 0.0055). BDNF infusion into the hippocampus prior to LPS injection prevented the reduction in Bdnf, Sst, and Cort mRNA expression. BDNF also prevented the LPS-induced effect on protein levels of BDNF, SST and NPY. BDNF prevention of LPS effects occurred in the context of sustained elevation of inflammatory markers (interleukin 1-beta and glial fibrillary acidic protein). BDNF may protect SST GABAergic interneurons from LPS-induced inflammation, providing novel insights into the molecular mechanisms linking inflammation and GABAergic dysfunction in neuropsychiatric diseases.
Keywords: Brain-Derived Neurotrophic Factor, lipopolysaccharide, GABAergic interneurons, Inflammation, neuropsychiatric disorders
Received: 28 Jul 2025; Accepted: 10 Sep 2025.
Copyright: © 2025 Rezaei, Banasr, Prevot, Bansal, Vieira and Sibille. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Etienne Sibille, Centre for Addiction and Mental Health, Toronto, Canada
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