Abstract

Panic Disorder (PD) is a common anxiety disorder characterized by sudden, unpredictable, and intense episodes of fear, autonomic, and respiratory responses. In the early stages of PD, patients generally experience untriggered panic attacks that eventually develop into phobic avoidance behaviors. The underlying mechanisms of these panic attacks are unknown, though studies suggest  a perceived threat to homeostasis may act as a primary trigger. One such homeostatic threat in panic-vulnerable individuals is acidosis, commonly induced via CO2-inhalation. This experiment investigates the acid-sensing G-protein coupled receptor (GPCR) T-cell death-associated gene 8 (TDAG8) in panic pathophysiology. Using TDAG8 KO mice, we investigated the role of interleukin-1β (IL-1β) in panic-associated fear response. We hypothesized that microglial activation and IL-1β are relevant for translating acidosis to fear. Post-behavioral immunohistochemistry and confocal microscopy were used to acquire 3-dimensional images of microglia in the circumventricular organs (CVOs) of the mouse brain. We concluded IL-1β is sufficient to generate significant fear in the absence of CO2, acidosis, and the acid sensor TDAG8. Additionally, we found activated microglial cells in the CVOs can be distinguished from inactive microglia by examining the shape, volume of the cell body, length of projections, and number of branching projections.  Further research will utilize IL-1β antagonists in WT mice to extinguish fear response. They may be important for the treatment of PD in addition to TDAG8 and anti-inflammatory microglial blockers.