The Role of the Spleen in the Re-Establishment of Brain-Macrophage Trafficking and Anxiety-Like Behavior in Stress-Sensitized Mice
Year: 2015
Type: dissertation
Abstract: Psychosocial stress is associated with immune dysfunction and anxiety. Previous studies demonstrated that stress-induced bone marrow-derived monocytes trafficked to the brain and contributed to neuroinflammation and prolonged anxiety following repeated social defeat (RSD). Moreover, 24 days post RSD, mice remained stress-sensitized (SS) to acute stress. For example, acute stress in SS mice caused monocyte trafficking from the spleen to the brain that promoted increased neuroinflammation and the re-establishment of prolonged anxiety. Therefore, we hypothesize that a unique monocyte population in the spleens of SS mice was released into circulation by acute stress leading to neuroinflammation and anxiety. Thus, we sought to ascertain the effects of splenectomy on brain-macrophage trafficking and anxiety in SS mice exposed to acute stress 24 days following initial exposure to RSD. Preliminary studies indicated that removal of the spleen two weeks before RSD did not affect stress-induced neuroinflammation or anxiety. However, splenectomy prevented the re-establishment of brain-macrophage trafficking, neuroinflammation and anxiety in SS mice following acute stress. Furthermore, because the spleen is innervated by the sympathetic nervous system (SNS), we sought to determine the degree to which ablation of the SNS would prevent the release of monocytes from the spleen. To prevent SNS-mediated release of splenic myeloid cells, guanethidine (50mg/kg) was injected prior to acute stress 24 days after initial exposure to RSD. Guanethidine treatment reduced the release of monocytes in circulation, reduced brain-macrophage trafficking, diminished brain cytokine expression and anxiety in SS mice. Taken together, these data demonstrate that the spleen is a key reservoir of inflammatory monocytes that play a role in the reactivation of anxiety. This observation may provide a potential target for intervention in prolonged anxiety and perhaps posttraumatic stress disorder.
Author: Jenna M. Patterson
Language: English
Subfield: Behavioral Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W210054977