Demyelination in the juvenile period, but not in adulthood, leads to long-lasting cognitive impairment and deficient social interaction in mice

Makinodan, Manabu; Yamauchi, Takahira; Tatsumi, Kouko; Okuda, Hiromichi; Takeda, Tomohiko; Kiuchi, Kuniaki; Sadamatsu, Miyuki; Wanaka, Akio; Kishimoto, Toshifumi

doi:10.1016/j.pnpbp.2009.05.006

Cited by 74 publications

(64 citation statements)

References 39 publications

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“…Furthermore, mice fed with cuprizone and treated with minocycline demonstrated an improved motor coordination than cuprizone fed and sham treated mice as the time to tranverse the narrow beam was shorter after 5 and 6 weeks of cuprizone feeding. In the holeboard testing no significant treatment effects were found for locomotor activity and exploratory like behaviour, which is consistent with the findings of Makinodan et al [41]. In this recently published work no differences were found for locomotor activity and exploration in the open field test and the elevated plus maze test in 8-week old mice fed with cuprizone.…”

Section: Discussionsupporting

confidence: 92%

Beneficial Effects of Minocycline on Cuprizone Induced Cortical Demyelination

et al. 2010

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In this study, we investigated the potential of minocycline to influence cuprizone induced demyelination in the grey and white matter. To induce demyelination C57BL/6 mice were fed with cuprizone for up to 6 weeks and were analysed at different timepoints (week 0, 4, 5, 6). Mice treated with minocycline had less demyelination of the cortex and corpus callosum compared with sham treated animals. In the cortex decreased numbers of activated and proliferating microglia were found after 6 weeks of cuprizone feeding, while there were no significant effects for microglial infiltration of the corpus callosum. In addition to the beneficial effects on demyelination, minocycline prevented from motor coordination disturbance as shown in the beam walking test. For astrogliosis and the numbers of OPC and oligodendrocytes no treatment effects were found. In summary, minocycline treatment diminished the course of demyelination in the grey and white matter and prevented disturbances in motor coordination.

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Section: Discussionsupporting

confidence: 92%

Beneficial Effects of Minocycline on Cuprizone Induced Cortical Demyelination

et al. 2010

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“…For instance, a high comorbidity between multiple sclerosis and anxiety has been described [55]. Myelin deficiency in the juvenile period of mice impairs cognitive functions and leads to altered social interaction [56]. Early weaning increases anxiety and is associated with developmental changes in myelin formation in the prefrontal cortex, in the hippocampus [57] and in the amygdala [58] of mice and rats.…”

Section: Discussionmentioning

confidence: 99%

Changes in Object Recognition and Anxiety-Like Behaviour in Mice Expressing a Cx47 Mutation That Causes Pelizaeus-Merzbacher-Like Disease

Zlomuzica¹,

Tress²,

Binder³

et al. 2012

Dev Neurosci

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Pelizaeus-Merzbacher-like disease is characterized by impaired psychomotor development, ataxia, progressive spasticity and mental retardation. It is induced by mutations in the gap junction gene GJC2 that encodes for the gap junction protein connexin 47. Mice bearing a human Cx47M283T missense mutation have been generated as a transgenic mouse model of Pelizaeus-Merzbacher-like disease. Homozygous expression of the mutant connexin 47 gene in oligodendrocytes resulted in a complex and variable neuropathologic phenotype, which was associated with impairments in motor coordination in juvenile, but not adult mice. In the present study, we have investigated anxiety-like behaviour and spatial working memory in juvenile (P23) and adult (3-month-old) Cx47M282T mutant mice. Adult Cx47M282T mice were also evaluated in terms of neuromotor functions and in the novel object recognition test. Juvenile Cx47M282T mutant mice exhibited an increase in anxiety-like behaviour in the open field test, but no changes in spatial working memory performance. No significant changes in anxiety-like behaviour, spatial working memory or neuromotor functions were observed in the adult Cx47M282T mutant mice. However, novel object recognition was significantly impaired in adult Cx47M282T mice. Our results suggest that the expression of the human Cx47M282T mutation in the mouse causes changes in anxiety-like behaviour in juvenile and novel object recognition impairments in adult mice. It appears that the distortion of panglial gap junction coupling in white and grey matter tissue in the Cx47M282T mice is associated with a complex age-dependent behavioural phenotype including changes in psychomotor, emotional and memory functions.

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“…This includes perinatal and subchronic administration of phencyclidine, [70][71][72][73][74] ), early social isolation, 80 and excitotoxic developmental lesion models (medial prefrontal 81 ). Cuprizone, a copper chelating agent that actively disrupts myelination, results in diminished social interaction in mice, [81][82][83][84][85][86] but only when dys myelination occurs before adult life. 83 Guest and colleagues 87 have recently shown that dizocilpine (also known as MK-801, an N-methyl-d-aspartate receptor [NMDAr] antagonist and pharmacological model of schizophrenia 88 ), primarily affects the metabolic processes of oligodendrocytes rather than neurons in vitro.…”

Section: The Role Of Myelin In Morphometrymentioning

confidence: 99%

“…Cuprizone, a copper chelating agent that actively disrupts myelination, results in diminished social interaction in mice, [81][82][83][84][85][86] but only when dys myelination occurs before adult life. 83 Guest and colleagues 87 have recently shown that dizocilpine (also known as MK-801, an N-methyl-d-aspartate receptor [NMDAr] antagonist and pharmacological model of schizophrenia 88 ), primarily affects the metabolic processes of oligodendrocytes rather than neurons in vitro. Clozapine, a drug with some therapeutic effect on negative symptoms, 89 counters the metabolic effects of MK-801, but again, preferentially in oligodendrocytes rather than neurons/ astrocytes.…”

Section: The Role Of Myelin In Morphometrymentioning

confidence: 99%