Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models
Fig 5
Microglial depletion down-regulates TNF-α expression and prevents noise-induced tinnitus.
A. Treatment with PLX3397 suppressed the TNF-α mRNA level in AI and prevented noise-induced increases in TNF-α expression 12 hours after noise exposure. Control mice (n = 4) that had undergone PLX3397 treatment and sham exposure had a lower TNF-α mRNA level compared to naïve mice (n = 7). In PLX 3397-treated mice (n = 4), noise exposure did not significantly increase TNF-α expression in AI of either hemisphere. * indicates P < 0.05 compared to naïve. B. Behavioral evidence of tinnitus was evaluated with gap detection. Behavioral tests were conducted at four time points: 1) before PLX 3397 treatment (naïve), 2) after 21 days of PLX3397 treatment (PLX), 3) after noise exposure and still with PLX 3397 treatment (PLX/post noise), and 4) after 7 days of washout of PLX3397 (post noise/PLX washout). Microglial depletion improved basal-level gap detection and prevented noise exposure–induced impairment in gap detection as observed in wild-type mice in Fig 3C. *, **, and *** indicate P < 0.05, P < 0.01, and P < 0.001, respectively. C. Animals’ ability to hear tones, which was measured with PPI, was not altered by PLX treatment or noise exposure (treatment effect, P = 0.15). Data associated with this figure can be found in S1 Data. Error bars represent SEM. PPI, prepulse inhibition; TNF-α, tumor necrosis factor alpha.