4.6 Article

The effects of a novel inhibitor of tumor necrosis factor (TNF) alpha on prepulse inhibition and microglial activation in two distinct rodent models of schizophrenia

期刊

BEHAVIOURAL BRAIN RESEARCH
卷 406, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.bbr.2021.113229

关键词

Tumor necrosis factor-alpha (TNF?); Schizophrenia; Neuroinflammation; Dopamine D2 receptor; Microglia; Prepulse inhibition; Sensorimotor gating; Poly I; C

资金

  1. P2D Bioscience, Inc., Cincinnati, OH

向作者/读者索取更多资源

The study evaluated a new immune modulator PD2024 targeting TNF-α to alleviate sensorimotor gating deficits and microglial activation in two different rodent models of schizophrenia. The results suggest that targeting brain TNF-α may be a viable pharmacological approach to treat neuroinflammation associated with schizophrenia.
Increased neuroinflammation has been shown in individuals diagnosed with schizophrenia (SCHZ). This study evaluated a novel immune modulator (PD2024) that targets the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF?) to alleviate sensorimotor gating deficits and microglial activation employing two different rodent models of SCHZ. In Experiment 1, rats were neonatally treated with saline or the dopamine D2-like agonist quinpirole (NQ; 1 mg/kg) from postnatal day (P) 1-21 which produces increases of dopamine D2 receptor sensitivity throughout the animal?s lifetime. In Experiment 2, rats were neonatally treated with saline or the immune system stimulant polyinosinic:polycytidylic acid (Poly I:C) from P5-7. Neonatal Poly I:C treatment mimics immune system activation associated with SCHZ. In both experiments, rats were raised to P30 and administered a control diet or a novel TNF? inhibitor PD2024 (10 mg/kg) in the diet from P30 until P67. At P4546 and from P60-67, animals were behaviorally tested on auditory sensorimotor gating as measured through prepulse inhibition (PPI). NQ or Poly I:C treatment resulted in PPI deficits, and PD2024 treatment alleviated PPI deficits in both models. Results also revealed that increased hippocampal and prefrontal cortex microglial activation produced by neonatal Poly I:C was significantly reduced to control levels by PD2024. In addition, a separate group of animals neonatally treated with saline or Poly I:C from P5-7 demonstrated increased TNF? protein levels in the hippocampus but not prefrontal cortex, verifying increased TNF? in the brain produced by Poly I:C. Results from this study suggests that that brain TNF? is a viable pharmacological target to treat the neuroinflammation known to be associated with SCHZ.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据