The pharmacological perturbation of brain zinc impairs BDNF-related signaling and the cognitive performances of young mice - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Scientific Reports Année : 2018

The pharmacological perturbation of brain zinc impairs BDNF-related signaling and the cognitive performances of young mice

Vanessa Castelli

Résumé

Abstract Zinc (Zn 2+ ) is a pleiotropic modulator of the neuronal and brain activity. The disruption of intraneuronal Zn 2+ levels triggers neurotoxic processes and affects neuronal functioning. In this study, we investigated how the pharmacological modulation of brain Zn 2+ affects synaptic plasticity and cognition in wild-type mice. To manipulate brain Zn 2+ levels, we employed the Zn 2+ (and copper) chelator 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, CQ). CQ was administered for two weeks to 2.5-month-old (m.o.) mice, and effects studied on BDNF-related signaling, metalloproteinase activity as well as learning and memory performances. CQ treatment was found to negatively affect short- and long-term memory performances. The CQ-driven perturbation of brain Zn 2+ was found to reduce levels of BDNF, synaptic plasticity-related proteins and dendritic spine density in vivo . Our study highlights the importance of choosing “when”, “where”, and “how much” in the modulation of brain Zn 2+ levels. Our findings confirm the importance of targeting Zn 2+ as a therapeutic approach against neurodegenerative conditions but, at the same time, underscore the potential drawbacks of reducing brain Zn 2+ availability upon the early stages of development.
Fichier principal
Vignette du fichier
s41598-018-28083-9.pdf (2.5 Mo) Télécharger le fichier
Origine Publication financée par une institution
Licence

Dates et versions

hal-04438161 , version 1 (05-02-2024)

Licence

Identifiants

Citer

Valerio Frazzini, Alberto Granzotto, Manuela Bomba, Noemi Massetti, Vanessa Castelli, et al.. The pharmacological perturbation of brain zinc impairs BDNF-related signaling and the cognitive performances of young mice. Scientific Reports, 2018, 8 (1), pp.9768. ⟨10.1038/s41598-018-28083-9⟩. ⟨hal-04438161⟩
19 Consultations
10 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More