Related Experiment Video
Updated: Dec 20, 2025
BS3 Chemical Crosslinking Assay: Evaluating the Effect of Chronic Stress on Cell Surface GABAA Receptor Presentation in the Rodent Brain
Published on: May 26, 2023
Diazepam limits microglia-mediated neuronal remodeling in the prefrontal cortex and associated behavioral
Justin L Bollinger1, Matthew J Horchar1, Eric S Wohleb2
1Department of Pharmacology & Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Abstract:
Chronic stress induces neuronal atrophy and synaptic loss in the medial prefrontal cortex (PFC), and this leads to behavioral and cognitive impairments. Our recent findings indicate that microglia contribute to structural remodeling of neurons via increased colony-stimulating factor (CSF)-1 in the medial PFC. Other work shows that chronic stress induces aberrant neuronal activity in the medial PFC, and that neuronal hyperactivity increases CSF1 signaling and alters microglia function. Thus, the present studies were designed to examine the role of neuronal activity in stress-induced CSF1 signaling and microglia-mediated neuronal remodeling in the medial PFC. Additional analyses probed stress effects on the dorsal hippocampus (HPC), basolateral amygdala (BLA), and somatosensory cortex (SSCTX). Mice were exposed to chronic unpredictable stress (CUS) or handled intermittently as controls, and received daily injection of vehicle or diazepam (1 mg/kg). As anticipated, diazepam attenuated CUS-induced behavioral despair and cognitive impairments. Further studies showed that diazepam normalized Csf1 and C3 mRNA in the PFC, and prevented increases in Csf1r and Cd11b in frontal cortex microglia following CUS. Stress had no effect on neuroimmune gene expression in the HPC. Confocal imaging in Thy1-GFP(M) mice demonstrated that diazepam limited microglial engulfment of neuronal elements and blocked CUS-induced dendritic spine loss in the medial PFC. Altogether, these findings indicate that modulation of chronic stress-induced neuronal activity limits microglia-mediated neuronal remodeling in the medial PFC, and subsequent behavioral and cognitive consequences.
Insights
Chronic stress harms the brain, causing cognitive issues. Reducing neuronal activity with diazepam can prevent stress-induced brain changes and cognitive deficits by modulating microglia.
Area of Science:
- Neuroscience
- Neuroimmunology
- Stress Research
Background:
- Chronic stress causes neuronal atrophy and cognitive impairments, particularly in the medial prefrontal cortex (mPFC).
- Microglia, immune cells in the brain, contribute to neuronal remodeling through colony-stimulating factor-1 (CSF-1) signaling.
- Neuronal hyperactivity in the mPFC under chronic stress alters microglia function and increases CSF1 signaling.
Purpose of the Study:
- To investigate the role of neuronal activity in stress-induced CSF1 signaling and microglia-mediated neuronal remodeling in the mPFC.
- To examine the effects of chronic stress and diazepam on neuroimmune gene expression in the mPFC, hippocampus, amygdala, and somatosensory cortex.
Main Methods:
- Mice were subjected to chronic unpredictable stress (CUS) and treated with vehicle or diazepam.
- Gene expression (Csf1, C3, Csf1r, Cd11b) was analyzed in the brain.
- Confocal imaging was used to assess microglial engulfment and dendritic spine loss in Thy1-GFP(M) mice.
Main Results:
- Diazepam attenuated CUS-induced behavioral despair and cognitive deficits.
- Diazepam normalized Csf1 and C3 mRNA levels in the PFC and prevented microglial changes (Csf1r, Cd11b) after CUS.
- Diazepam limited microglial engulfment of neuronal elements and blocked dendritic spine loss in the mPFC.
Conclusions:
- Modulating neuronal activity in the mPFC can limit microglia-mediated neuronal remodeling.
- Interventions targeting neuronal activity may mitigate the behavioral and cognitive consequences of chronic stress.
