The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations

International Journal of Molecular Sciences

Vincenzo Conte¹  Patrizia Sartori¹  Patrizia Procacci¹  Gianfranco Balboni²  Giada Amodeo³  Benedetta Verduci³  Paola Sacerdote³  Silvia Franchi³ 

[1] Department of Biomedical Sciences for Health, Università degli Studi di Milano, Via Colombo 71, 20133 Milan, Italy;Department of Life and Environmental Sciences, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy;Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Vanvitelli 32, 20129 Milan, Italy;

关键词: prokineticin system;    chemotherapy-induced side effects;    neuroinflammation;    neuropathic pain;    anxiety;    depression;   

DOI  :  10.3390/ijms221910256

来源: DOAJ

【 摘 要 】

The development of neuropathy and of mood alterations is frequent after chemotherapy. These complications, independent from the antitumoral mechanism, are interconnected due to an overlapping in their processing pathways and a common neuroinflammatory condition. This study aims to verify whether in mice the treatment with the proteasome inhibitor bortezomib (BTZ), at a protocol capable of inducing painful neuropathy, is associated with anxiety, depression and supraspinal neuroinflammation. We also verify if the therapeutic treatment with the antagonist of the prokineticin (PK) system PC1, which is known to contrast pain and neuroinflammation, can prevent mood alterations. Mice were treated with BTZ (0.4 mg/kg three times/week for 4 weeks); mechanical allodynia and locomotor activity were evaluated over time while anxiety (dark light and marble burying test), depression (sucrose preference and swimming test) and supraspinal neuroinflammation were checked at the end of the protocol. BTZ treated neuropathic mice develop anxiety and depression. The presence of mood alterations is related to the presence of neuroinflammation and PK system activation in prefrontal cortex, hippocampus and hypothalamus with high levels of PK2 and PKR2 receptor, IL-6 and TNF-α, TLR4 and an upregulation of glial markers. PC1 treatment, counteracting pain, prevented the development of supraspinal inflammation and depression-like behavior in BTZ mice.

【 授权许可】

Unknown