Gender influence on schizophrenia‐relevant abnormalities in a cuprizone demyelination model

Valeiras, Brenda; Siri, María Victoria Rosato; Codagnone, Martín Gabriel; Reinés, Analı́a; Pasquini, Juana M.

doi:10.1002/glia.22704

Cited by 17 publications

(5 citation statements)

References 59 publications

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“…The effect of cuprizone has been tested in other preclinical models of anxiety, including open field and light-dark tests. The majority of papers using the open field test showed that a cuprizone diet caused increased anxiety with decreased time or distance in the centre zone [ 55 , 70 , 72 , 75 , 76 , 79 , 80 , 81 , 82 ]; conversely, whereas, others found increased time in the centre [ 25 , 83 ] or no difference [ 35 , 84 ]. Using the light-dark test, mice fed a cuprizone diet spent less time in the light box, which is correlated to increased anxiety [ 70 , 85 ].…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice

et al. 2022

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Multiple sclerosis is an autoimmune disease characterised by demyelination in the central nervous system. The cuprizone-induced demyelination model is often used in mice to test novel treatments for multiple sclerosis. However, despite significant demyelination, behavioural deficits may be subtle or have mixed results depending on the paradigm used. Furthermore, the sex differences within the model are not well understood. In the current study, we have sought to understand the behavioural deficits associated with the cuprizone-induced demyelination model in both male and female C57BL/6J mice. Using Black gold II stain, we found that cuprizone administration over 6 weeks caused significant demyelination in the corpus callosum that was consistent across both sexes. Cuprizone administration caused increased mechanical sensitivity when measured using an electronic von Frey aesthesiometer, with no sex differences observed. However, cuprizone administration decreased motor coordination, with more severe deficits seen in males in the horizontal bar and passive wire hang tests. In contrast, female mice showed more severe deficits in the motor skill sequence test. Cuprizone administration caused more anxiety-like behaviours in males compared to females in the elevated zero maze. Therefore, this study provides a better understanding of the sex differences involved in the behavioural aspects of cuprizone-induced demyelination, which could allow for a better translation of results from the laboratory to the clinic.

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Section: Discussionmentioning

confidence: 99%

Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice

et al. 2022

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“…Some labs have also reported intoxicating their mice by oral gavage of solubilized cuprizone. While sex, genetic background, and age of the animals have been identified as important variables for the reproducibility and the extent of cuprizone-induced pathological changes [99][100][101], "weight" as a critical variable for reliable and consistent demyelination has just recently been systematically addressed. In a recent work, we have investigated this issue, and were able to show that animal weight is an important variable for reliable cuprizone-induced demyelination [102].…”

Section: Animal Weightmentioning

confidence: 99%

The Cuprizone Model: Dos and Do Nots

Zhan

Mann

Joost

et al. 2020

Cells

100

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Various pre-clinical models with different specific features of the disease are available to study MS pathogenesis and to develop new therapeutic options. During the last decade, the model of toxic demyelination induced by cuprizone has become more and more popular, and it has contributed substantially to our understanding of distinct yet important aspects of the MS pathology. Here, we aim to provide a practical guide on how to use the cuprizone model and which pitfalls should be avoided.

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“…Several models have examined how demyelination might induce the hyperdopaminergic state found in schizophrenic patients, involving a misbalance in glutamate . Altered myelination could correlate with an aberrant wiring network, which in turn triggers alterations in dopamine levels . Our results suggest that the timing of demyelination significantly influences the development of schizophrenia‐relevant behavior, particularly in adult males.…”

Section: Discussionmentioning

confidence: 74%

The Effects of Prenatal Iron Deficiency and Risperidone Treatment on the Rat Frontal Cortex: A Proteomic Analysis

et al. 2017

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Prenatal iron deficiency (pID) has been described to increase the risk for neurodevelopmental disorders such as autism and schizophrenia; however, the precise molecular mechanisms are still unknown. Here, we utilized high-throughput MS to examine the proteomic effects of pID in adulthood on the rat frontal cortex area (FCA). In addition, the FCA proteome was examined in adulthood following risperidone treatment in adolescence to see if these effects could be prevented. We identified 1501 proteins of which 100 were significantly differentially expressed in the FCA at postnatal day 90. Pathway analysis of proteins affected by pID revealed changes in metabolic processes, including the tricyclic acid cycle, mitochondrial dysfunction, and P13K/Akt signaling. Interestingly, most of these protein changes were not present in the adult pID offspring who received risperidone in adolescence. Considering the link between pID and several neurodevelopmental disorders such as autism and schizophrenia these presented results bring new perspectives to understand the role of iron in metabolic pathways and provide novel biomarkers for future studies of pID.

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Gender influence on schizophrenia‐relevant abnormalities in a cuprizone demyelination model

Cited by 17 publications

References 59 publications

Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice

Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice

The Cuprizone Model: Dos and Do Nots

The Effects of Prenatal Iron Deficiency and Risperidone Treatment on the Rat Frontal Cortex: A Proteomic Analysis

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