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SUMMARY:Neutrophil-Mediated Effects at the Blood Brain Barrier Following C
 hronic Stress  - Dr Stacey Kigar (Department of Medicine and Psychiatry\, 
 University of Cambridge)
DTSTART:20210314T113000Z
DTEND:20210314T122000Z
UID:TALK158134@talks.cam.ac.uk
CONTACT:Miroslava Novoveska
DESCRIPTION:YouTube link: https://youtu.be/cfcSFJg4ANc\n\nRegistration for
 m to attend Q&A session on Zoom: https://forms.gle/tTRQreym7s6pR2rW6\n\nCh
 ronic stress is a major risk factor for major depressive disorder (MDD) an
 d is associated with altered white blood cell (WBC) counts and increased c
 ytokine production. However\, the relationship between peripheral immune c
 hanges and altered mood is unclear\, as access to the CNS by peripheral WB
 Cs and cytokines is tightly regulated by the blood brain barrier (BBB). Un
 der conditions of homeostasis\, WBCs do not appreciably enter the parenchy
 ma\, instead residing in spaces just inside the BBB such as the leptomenin
 ges\, from which they surveil the CNS for pathogens or damage. Importantly
 \, cytokines released by WBCs from within this space may modulate behavior
  and neuronal activity\, as has recently been shown for type II interferon
 s and IL-17. We set out to characterize the dynamic profile of circulating
  and meningeal WBCs in mice undergoing chronic social defeat (CSD) stress\
 , a well-characterized mouse model for depressive-like behavior. We found 
 that a single social defeat encounter is sufficient to induce more than a 
 4x increase in the number of blood neutrophils\, consistent with reports t
 hat blood neutrophil levels rapidly increase following acute exposure to s
 tress via sympathetic innervation of bone marrow reservoirs. Conversely\, 
 acute stress had no effect on neutrophil prevalence in the leptomeningeal 
 compartment\; instead\, it took completion of the 14d CSD paradigm to see 
 an approximate 1.5x increase in meningeal neutrophils. Drop-seq analysis o
 f control vs. CSD meninges independently confirmed that stressed animals h
 ave more (~2x) neutrophils\, shown further by both high-dimensional flow c
 ytometry and immunohistochemical analysis. Our evidence suggests neutrophi
 l chemotaxis to the BBB can be blocked via administration of chemokine rec
 eptor-targeting antibodies\, which may in turn improve behavioral outcomes
  for chronically stressed mice. Given both that pharmacological interventi
 ons targeting serotonergic pathways are ineffective for a large swath of M
 DD patients – particularly those with increased peripheral inflammation
 —and recent reports that circulating neutrophil levels correlate strongl
 y with MDD symptom severity\, this data has exciting implications as a pot
 ential biomarker and future therapeutic target for treatment of depression
 .
LOCATION:Online
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