The Sound of Inflammation: Zebra Finch Brain, Memory and Songs Under Lipopolysaccharide-Induced Neuroinflammatory Stress

Abstract

Neuroinflammation has been increasingly recognized as a key modulator of neural functions and behavior. In this study, we investigated the dynamics of lipopolysaccharide (LPS)-induced neuroinflammation in male zebra finches. We focused on the change in two pro-inflammatory cytokines (Tumor Necrosis Factor Alpha (TNF-α) and Interleukine-1 Beta (IL-1β)) and the corticosterone, an anti-inflammatory stress hormone. Additionally, we studied the behavioral outcomes and songs of the birds. Male zebra finches were injected intra peritoneally with either LPS or Phosphate-buffered saline (PBS). Fold changes in gene expression levels of TNF-α and IL-1β were quantified using qRT-PCR in both the whole brain at multiple time points and the High vocal center (HVC) region at the peak inflammatory time determined based on the aforementioned whole brain studies. Corticosterone levels were assessed using Enzyme-Linked Immunosorbent Assay (ELISA). To evaluate the effect on the behavior and memory, acoustic features of song syllables were collected and analyzed after 10 days of chronic injections (LPS/PBS).

A significant peak in TNF-α and IL-1β cytokines in whole brain tissues was observed at two hours post-LPS injections (fold changes: 2.68 and 5.26, p-value=0.012 and p-value=0.0137, respectively), with expression levels decreasing thereafter. In contrast, no significant elevation of the same cytokines in the HVC region (p-values 0.34 and 0.26 respectively) was observed, however, corticosterone levels were significantly higher in LPS-treated birds (2.41 pg/mg vs. 1.16 pg/mg tissue, p-value=0.031). Chronic LPS exposure led to a significant alteration in the features including decreased pitch goodness, reduced entropy, frequency modulation (FM), amplitude modulation (AM), and mean frequency, along with increased amplitude. PBS-injected birds showed no changes.

Therefore, LPS Induces a rapid neuroinflammatory response in male zebra finches’ brain with no significant cytokine upregulation in the HVC but with elevated anti-inflammatory corticosterone levels. The chronic exposure to LPS induces impairments in song features indicating potential alterations in neural circuits related to memory and song production.