PMID- 30356873
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 1664-0640 (Print)
IS  - 1664-0640 (Electronic)
IS  - 1664-0640 (Linking)
VI  - 9
DP  - 2018
TI  - Loss of Microglia and Impaired Brain-Neurotrophic Factor Signaling Pathway in a 
      Comorbid Model of Chronic Pain and Depression.
PG  - 442
LID - 10.3389/fpsyt.2018.00442 [doi]
LID - 442
AB  - Major depressive disorder (MDD) and chronic pain are two complex disorders that 
      often coexist. The underlying basis for this comorbidity is unknown. In the 
      current investigation, microglia and the brain-derived neurotrophic factor 
      (BDNF)-cAMP response element-binding protein (CREB) pathway were investigated. A 
      comorbidity model, with characteristics of both MDD and chronic pain, was 
      developed by the administration of dextran sodium sulfate (DSS) and the induction 
      of chronic unpredictable psychological stress (CUS). Mechanical threshold sensory 
      testing and the visceromotor response (VMR) were employed to measure mechanical 
      allodynia and visceral hypersensitivity, respectively. RT-qPCR and western 
      blotting were used to assess mRNA and protein levels of ionized calcium-binding 
      adaptor molecule 1 (Iba-1), nuclear factor-kappa B (NF-kappaB), nuclear factor of 
      kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkappaBa), BDNF, 
      and CREB. In comorbid animals, mechanical allodynia and visceral 
      hypersensitivities were significant with increased mRNA and protein levels for 
      NF-kappaB-p65 and IkappaBa. Furthermore, the comorbid animals had deceased mRNA and 
      protein levels for Iba-1, BDNF, and CREB as well as a reduced number and density 
      of microglia in the medial prefrontal cortex (mPFC). These results together 
      suggest that DSS and CUS can induce the comorbidities of chronic pain and 
      depression-like behavior. The pathology of this comorbidity involves loss of 
      microglia within the mPFC with subsequent activation of NF-kappaB-p65 and 
      down-regulation of BDNF/p-CREB signaling.
FAU - Zhu, Cuizhen
AU  - Zhu C
AD  - Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Xu, Jinjie
AU  - Xu J
AD  - Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Lin, Yezhe
AU  - Lin Y
AD  - Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Ju, Peijun
AU  - Ju P
AD  - Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Duan, Dongxia
AU  - Duan D
AD  - Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Luo, Yanjia
AU  - Luo Y
AD  - Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Ding, Wenhua
AU  - Ding W
AD  - Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Huang, Shengnan
AU  - Huang S
AD  - Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Chen, Jinghong
AU  - Chen J
AD  - Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Cui, Donghong
AU  - Cui D
AD  - Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20181004
PL  - Switzerland
TA  - Front Psychiatry
JT  - Frontiers in psychiatry
JID - 101545006
PMC - PMC6190863
OTO - NOTNLM
OT  - BDNF
OT  - chronic pain
OT  - comorbidity
OT  - depression
OT  - microglia
EDAT- 2018/10/26 06:00
MHDA- 2018/10/26 06:01
PMCR- 2018/10/04
CRDT- 2018/10/26 06:00
PHST- 2018/03/23 00:00 [received]
PHST- 2018/08/28 00:00 [accepted]
PHST- 2018/10/26 06:00 [entrez]
PHST- 2018/10/26 06:00 [pubmed]
PHST- 2018/10/26 06:01 [medline]
PHST- 2018/10/04 00:00 [pmc-release]
AID - 10.3389/fpsyt.2018.00442 [doi]
PST - epublish
SO  - Front Psychiatry. 2018 Oct 4;9:442. doi: 10.3389/fpsyt.2018.00442. eCollection 
      2018.