Journal: Journal of Neuroinflammation

Article Title: Sleep deprivation induces anxiety-like behaviors through IL-6 driven astrocyte-GABAergic neuron crosstalk in the PAG-ACC circuit

doi: 10.1186/s12974-026-03879-z

Figure Lengend Snippet: Sleep deprivation induced anxiety-like behaviors and increased pro-inflammatory cytokine IL-6 in blood and midbrain. A Schematic diagram of the behavioral experimental paradigm. B Representative heatmaps of mouse movement in the open field test (OFT) in the control group and the sleep deprivation (SD) group. C The number of entries into the center zone and the time spent in the center zone during the OFT ( n = 10). D Representative heatmaps of mouse movement in the elevated plus maze (EPM) test in the control group and the SD group. E The number of entries into the open arms and the time spent in the open arms during the EPM test ( n = 10). F Flowchart illustrating the timeline for tissue collection. G-I Serum concentrations of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in the control group ( n = 6) and the SD group ( n = 10). J-M mRNA expression levels of IL-1β , IL-6 , and TNF-α in the cerebral cortex, thalamus, midbrain and oblongata in both groups ( n = 4). N Representative immunofluorescence images showing co‑localization of Iba1 and IL‑6 in the midbrain after sleep deprivation (SD). Scale bar:50 μm. O Representative immunofluorescence images of Iba1 expression after treatment with PLX5622 or control diet. Scale bar: 50 μm. P Representative heatmaps of mouse movement in the OFT in the control group and the PLX5622‑treated group. Q The number of entries into the center zone and the time spent in the center zone during the OFT ( n = 10). R Representative heatmaps of mouse movement in the EPM test in the control group and the PLX5622‑treated group. S The number of entries into the open arms and the time spent in the open arms during the EPM test ( n = 10). Data were presented as mean ± SEM; * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001

Article Snippet: Following a 7-day recovery, the solution of IL-6 receptor antagonist (IL-6Ra) (HY- P10284 , MedChemExpress, USA), GABA receptor antagonist (GABARa) (HY-W008645, MedChemExpress, USA), NMDA receptor antagonist AP5 (HY-100714 A, MedChemExpress, USA), AMPA receptor antagonist CNQX (HY-15066, MedChemExpress, USA) or vehicle was administered using a micro-infusion pump connected to an internal injector (R462, RWD Life Science, China) that extended 0.5 mm beyond the tip of the guide cannula.

Techniques: Control, Expressing, Immunofluorescence

Journal: Journal of Neuroinflammation

Article Title: Sleep deprivation induces anxiety-like behaviors through IL-6 driven astrocyte-GABAergic neuron crosstalk in the PAG-ACC circuit

doi: 10.1186/s12974-026-03879-z

Figure Lengend Snippet: IL-6- signaling Inhibition in the PAG rescued SD-induced anxiety-like behaviors. A Representative immunofluorescence images showing c-Fos expression in the periaqueductal gray (PAG) in the control group and the sleep deprivation (SD) group. Scale bar: 100 μm. B Quantification of c-Fos-positive cells in the PAG and other brain regions following SD. C Representative immunofluorescence images of c-Fos expression in the PAG 3 h after intravenous injection of saline or IL-6. D Quantitative analysis of c-Fos-positive cells in the PAG after saline or IL-6 treatment ( n = 5). E Representative heatmaps of mouse movement in the open field test (OFT) 3 h after saline or IL-6 treatment. F The number of entries into the center zone and the total time spent in the center zone during the OFT ( n = 8). G Representative heatmaps of mouse movement in the elevated plus maze (EPM) test 3 h after saline or IL-6 treatment. H The number of entries into the open arms and the total time spent in the open arms during the EPM test ( n = 8). I Schematic diagram and timeline of the drug micro-infusion into the PAG, and a representative image verifying the cannula placement. J Representative heatmaps of movement tracing in the OFT following micro-infusion of an IL-6 receptor antagonist or its isotype control. K The number of entries into center zone and the total time spent in the center zone ( n = 8). L Representative heatmaps of movement tracing in the EPM test following micro-infusion of the IL-6 receptor antagonist or isotype control. M The number of entries into the open arms and the total time spent in the open arms ( n = 8). Data were presented as mean ± SEM; * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001

Article Snippet: Following a 7-day recovery, the solution of IL-6 receptor antagonist (IL-6Ra) (HY- P10284 , MedChemExpress, USA), GABA receptor antagonist (GABARa) (HY-W008645, MedChemExpress, USA), NMDA receptor antagonist AP5 (HY-100714 A, MedChemExpress, USA), AMPA receptor antagonist CNQX (HY-15066, MedChemExpress, USA) or vehicle was administered using a micro-infusion pump connected to an internal injector (R462, RWD Life Science, China) that extended 0.5 mm beyond the tip of the guide cannula.

Techniques: Inhibition, Immunofluorescence, Expressing, Control, Injection, Saline

Journal: Journal of Neuroinflammation

Article Title: Sleep deprivation induces anxiety-like behaviors through IL-6 driven astrocyte-GABAergic neuron crosstalk in the PAG-ACC circuit

doi: 10.1186/s12974-026-03879-z

Figure Lengend Snippet: Sleep deprivation induces anxiety-like behaviors through IL-6-driven astrocyte-GABAergic neuron crosstalk in the PAG-ACC circuit. Sleep deprivation (SD) increased IL-6 systemically and in periaqueductal gray (PAG). Elevated IL‑6 induced morphological activation of PAG astrocytes, characterized by increased branch number and length, and enhanced astrocytic calcium activity. Activated astrocytes subsequently released more glutamate, which stimulated postsynaptic NMDA receptors on PAG neurons, induced upregulation of mesencephalic astrocyte‑derived neurotrophic factor (Manf). Increased Manf in turn reduced the expression of the GABA A receptor α1 subunit (Gabra1), thereby disinhibiting GABAergic neurons in the PAG and enhancing GABAergic transmission from the PAG to the anterior cingulate cortex (ACC). This SD-induced circuit-level dysregulation ultimately contributed to anxiety-like behaviors

Article Snippet: Following a 7-day recovery, the solution of IL-6 receptor antagonist (IL-6Ra) (HY- P10284 , MedChemExpress, USA), GABA receptor antagonist (GABARa) (HY-W008645, MedChemExpress, USA), NMDA receptor antagonist AP5 (HY-100714 A, MedChemExpress, USA), AMPA receptor antagonist CNQX (HY-15066, MedChemExpress, USA) or vehicle was administered using a micro-infusion pump connected to an internal injector (R462, RWD Life Science, China) that extended 0.5 mm beyond the tip of the guide cannula.

Techniques: Activation Assay, Activity Assay, Expressing, Transmission Assay