Fig. 4: IL-1RA treatment prevents long-term attention deficits and shapes mPFC microglia morphology following PA. | Neuropsychopharmacology

Fig. 4: IL-1RA treatment prevents long-term attention deficits and shapes mPFC microglia morphology following PA.

From: Inflammatory mechanisms contribute to long-term cognitive deficits induced by perinatal asphyxia via interleukin-1

Fig. 4

A Experimental design for the short- and long-term assessment of targeted IL-1RA treatment. In experiment 3, long-term behavioural and histological outcomes of IL-1RA treatment were examined. In experiment 4, acute changes caused by PA and IL-1RA in microglia morphology were examined in the mPFC 24 h after PA. In experiment 5, gene expression changes caused by PA and IL-1RA were examined in mPFC via RNA sequencing analysis, 24 h post-PA. B, C 5-CSRTT reveals a rescue effect of IL-1RA on attention and learning deficits in adult PA animals (trial day F(2.203,96.95), p < 0.001; treatment F(3,44) = 3.421, p = 0.025; trial day × treatment interaction F(87,1276) = 2.786, p < 0.001). D The elevated plus maze (EPM) test shows no effect of IL-1RA on anxiety levels in PA animals (PA treatment F(1,50) = 4.242, p = 0.044, IL-1RA treatment F(1,50) = 0.022, p = 0.882). E–H Microglia morphology analysis 24 h post-PA in the PRL revealed a marked shaping effect of IL-1RA treatment on microglia soma size in PA animals (PA treatment F(1, 2050) = 2.810, p = 0.093; IL-1RA treatment F(1, 2098) = 2.875, p = 0.090; PA × IL-1RA interaction F(1, 2864) = 16.196, p < 0.001). Furthermore, PA led to decreased microglia branching (ramification index PA treatment F(1, 30.44) = 5.677, p = 0.017, IL-1RA treatment F(1,0.209) = 0.038, p = 0.843, PA × IL-1RA interaction F(1, 3.940) = 0.734, p = 0.391), unchanged by IL-1RA. In the IL, PA significantly increased soma size with no substantial shaping effect of IL-1RA (PA treatment F(1, 17783) = 15.043, p < 0.001, IL-1RA treatment F(1, 2875) = 2.986, p = 0.08, PA × IL-1RA interaction F(1, 173.14) = 0.179, p = 0.672). However, PA and IL-1RA treatment had a significant interactive effect on branch ramification (ramification index: PA treatment F(1, 25.8) = 4.555, p = 0.032, IL-1RA treatment F(1, 2.359) = 0.416, p = 0.518, PA × IL-1RA interaction F(1, 3887) = 4.556, p = 0.041). I, J Inhibitory synapse numbers showed significant increase in both PRL and IL of PA animals, while acute IL-1RA treatment showed a long-term therapeutic effect only in the IL (IL: PA treatment F(1,156) = 7.762, p = 0.005; IL-1RA treatment F(1,156) = 10.886, p = 0.001, PA × IL-1RA treatment interaction F(1,156) = 3.564, p = 0.06; PRL: PA treatment F(1,151) = 4.286, p = 0.04; IL-1RA treatment F(1,151) = 0.586, p = 0.44, PA × IL-1RA treatment interaction F(1,151) = 0.785, p = 0.376). Data regarding inhibitory synapses are shown as normalised bouton densities across experimental groups with median and quartiles on (I, J). 5-CSRTT 5-choice serial reaction time task, IL infralimbic cortex, PRL prelimbic cortex. Error bars represent mean + SEM; * PA treatment effect, # IL-1RA treatment effect, & PA × IL-1RA interaction effect.

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