MCC950 Reduces the Anxiodepressive-like Behaviors and Memory Deficits Related to Paclitaxel-Induced Peripheral Neuropathy in Mice
Martínez-Martel, Ignacio (Institut de Recerca Sant Pau)
Negrini Ferrari, Sylmara Esther (Universitat Autònoma de Barcelona. Institut de Neurociències)
Pol, Olga (Universitat Autònoma de Barcelona. Institut de Neurociències)

Data:	2025
Descripció:	21 pàg.
Resum:	Chemotherapy-induced peripheral neuropathy and the accompanying affective disorders are serious side effects, and their resolution is not guaranteed. Oxidative stress and elevated levels of Nod-like receptor protein 3 (NLRP3) have been detected in the peripheral and central nervous systems of animals with neuropathic pain provoked by several antineoplastic drugs, such as paclitaxel (PTX). Several studies have further indicated that NLRP3 inflammasome inhibition could be an approach for treating chronic pain, but its impact on the anxiodepressive-like behaviors and memory deficits related to PTX-provoked neuropathy has not yet been investigated. MCC950 is a potent and specific inhibitor of the NLRP3 pathway that acts through inhibiting NLRP3 activation and inflammasome formation. We hypothesized that the administration of MCC950 could alleviate the affective and cognitive disorders accompanying PTX-provoked neuropathy. Using male C57BL/6 mice, we assessed the effects of MCC950 on the mechanical and thermal allodynia, anxiodepressive-like behavior, and memory deficits incited by this taxane. The results indicated that the intraperitoneal administration of 10 mg/kg of MCC950 twice daily for three consecutive days fully reversed the PTX-induced mechanical and thermal allodynia. This treatment also completely attenuated the anxiolytic (p < 0. 004) and depressive-like behaviors (p < 0. 022) and memory deficits (novel object recognition test; p < 0. 0018) incited by PTX. These actions were mainly achieved through blocking NLRP3 inflammasome activation in the sciatic nerve, amygdala, and hippocampus, and oxidative stress in the amygdala and hippocampus. MCC950 also normalized the p-ERK 1/2 overexpression in the sciatic nerve and apoptotic responses in the sciatic nerve and the amygdala. This study suggests that MCC950 might be a promising treatment for PTX-induced mental illnesses and neuropathy.
Ajuts:	Instituto de Salud Carlos III PI21/00592
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Anxiety ; Depression ; MCC950 ; Memory ; Neuropathic pain ; NLRP3 inflammasome ; Oxidative stress ; Paclitaxel
Publicat a:	Antioxidants, Vol. 14, Núm. 2 (January 2025) , p. 143, ISSN 2076-3921

DOI: 10.3390/antiox14020143
PMID: 40002330

21 p, 4.3 MB

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