PMID- 31064292
OWN - NLM
STAT- MEDLINE
DCOM- 20201110
LR  - 20201110
IS  - 1557-9042 (Electronic)
IS  - 0897-7151 (Print)
IS  - 0897-7151 (Linking)
VI  - 36
IP  - 21
DP  - 2019 Nov 1
TI  - Systemic Inhibition of Soluble Tumor Necrosis Factor with XPro1595 Exacerbates a 
      Post-Spinal Cord Injury Depressive Phenotype in Female Rats.
PG  - 2964-2976
LID - 10.1089/neu.2019.6438 [doi]
AB  - Spinal cord injury (SCI) is associated with a three-fold risk of major depressive 
      disorder compared with the general population. Current antidepressant therapy is 
      often not as effective in this patient population, suggesting the need for a more 
      efficacious therapeutic target. The goal of this study was to elucidate the role 
      of inflammatory cytokine tumor necrosis factor (TNF) in the dorsal raphe nucleus 
      (DRN, the principle source of serotonin to the brain) in the development and 
      possible treatment of depression after SCI. A depressive phenotype following 
      moderate T9 contusion was identified in adult female rats using a battery of 
      behavioral tests (forced swim test, sucrose preference test, novel object 
      recognition test, open field locomotion, and social exploration). Data revealed 
      two clusters of injured rats (58%) that exhibit increased immobility in the 
      forced swim test, indicating depressive phenotype or a melancholic-depressive 
      phenotype with concomitant decrease in sucrose preference. ElevatedTNF levels in 
      the DRN of these two clusters correlated with increased immobility in the forced 
      swim test. We then tested the efficacy of soluble TNF inhibition with XPro1595 
      treatment to prevent the depressive phenotype after SCI. Subcutaneous (s.c.) 
      delivery of XPro1595 caused an exacerbation of depressive phenotype, with all 
      treated clusters exhibiting increased forced swim immobility compared with 
      saline-treated non-depressed rats. Intracerebroventricular (i.c.v.) 
      administration of the drug did not prevent or enhance the development of 
      depression after injury. These results suggest a complex role for TNF-based 
      neuroinflammation in SCI-induced depression that needs to be further explored, 
      perhaps in conjunction with a broader targeting of additional post-SCI 
      inflammatory cytokines.
FAU - Farrell, Kaitlin
AU  - Farrell K
AD  - Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research 
      Center, Drexel University College of Medicine, Philadelphia, Pennsylvania.
FAU - Houle, John D
AU  - Houle JD
AD  - Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research 
      Center, Drexel University College of Medicine, Philadelphia, Pennsylvania.
LA  - eng
GR  - F30 NS101873/NS/NINDS NIH HHS/United States
GR  - P01 NS055976/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190710
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (XENP 1595)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Depression/*etiology/physiopathology
MH  - Female
MH  - Phenotype
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spinal Cord Injuries/physiopathology/*psychology
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/pharmacology
PMC - PMC6791477
OTO - NOTNLM
OT  - TNF
OT  - depression
OT  - neuroinflammation
OT  - spinal cord injury
COIS- No competing financial interests exist
EDAT- 2019/05/09 06:00
MHDA- 2020/11/11 06:00
PMCR- 2020/11/01
CRDT- 2019/05/09 06:00
PHST- 2019/05/09 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2019/05/09 06:00 [entrez]
PHST- 2020/11/01 00:00 [pmc-release]
AID - 10.1089/neu.2019.6438 [pii]
AID - 10.1089/neu.2019.6438 [doi]
PST - ppublish
SO  - J Neurotrauma. 2019 Nov 1;36(21):2964-2976. doi: 10.1089/neu.2019.6438. Epub 2019 
      Jul 10.