Behavioural changes observed in demyelination model shares similarities with white matter abnormalities in humans

Serra-de-Oliveira, Nathalia; Boilesen, Sabine Nunes; Carvalho, Carolina Prado de França; LeSueur-Maluf, Luciana; Zollner, Ricardo de Lima; Spadari, Regina Célia; Medalha, Carla Cristina; Castro, Gláucia Monteiro de

doi:10.1016/j.bbr.2015.03.038

Cited by 36 publications

(23 citation statements)

References 63 publications

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“…It has been confirmed that motor dysfunction is a crucial problem in patient with MS (Coghe et al ., ), and CPZ model mice have severe motor dysfunction (Franco‐Pons et al ., ; Hibbits et al ., ; Li et al ., ), an impairment of spatial working memory ( Xiao et al ., ; Adilijiang et al ., ), and a diminishing of social interaction (Brunet‐Gouet & Decety, ). Recently, Lewis rats fed with CPZ exhibited demyelination and behavioral changes that are similar to white matter abnormalities observed in humans (Serra‐de‐Oliveria et al ., ). The abnormal behaviors, demyelination, and oligodendrocyte loss observed in CPZ‐treated mice suggests a conjunction between white matter damage and behavioral disorder symptoms.…”

Section: Discussionmentioning

confidence: 97%

miR‐219 attenuates demyelination in cuprizone‐induced demyelinated mice by regulating monocarboxylate transporter 1

Liu

Ren²,

et al. 2017

Eur J of Neuroscience

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Remyelination is limited in patients with multiple sclerosis (MS) due to the difficulties in recruiting proliferating oligodendrocyte precursors (OPCs), the inhibition of OPC differentiation and/or maturation, and/or failure in the generation of the myelin sheath. In vitro studies have revealed that miR-219 is necessary for OPC differentiation and monocarboxylate transporter 1 (MCT1) plays a vital role in oligodendrocyte maturation and myelin synthesis. Herein, we hypothesized that miR-219 might promote oligodendrocyte differentiation and attenuate demyelination in a cuprizone (CPZ)-induced demyelinated model by regulating the expression of MCT1. We found that CPZ-treated mice exhibited significantly increased anxiety in the open field test. However, miR-219 reduced anxiety as shown by an increase in the total distance, the central distance and the mean amount of time spent in the central area. miR-219 decreased the quantity of OPCs and increased the number of oligodendrocytes and the level of myelin basic protein (MBP) and cyclic nucleotide 3' phosphodiesterase (CNP) protein. Ultrastructural studies further confirmed that the extent of demyelination was attenuated by miR-219 overexpression. Meanwhile, miR-219 also greatly enhanced MCT1 expression via suppression of oligodendrocyte differentiation inhibitors, Sox6 and Hes5, treatment with the MCT1 inhibitor α-cyano-4-hydroxycinnamate (4-CIN) reduced the number of oligodendrocytes and the protein levels of MBP and CNP. Taken together, these results suggest a novel mode of action of miR-219 via MCT1 in vivo and may provide a new potential remyelination therapeutic target.

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Section: Discussionmentioning

confidence: 97%

miR‐219 attenuates demyelination in cuprizone‐induced demyelinated mice by regulating monocarboxylate transporter 1

Liu

Ren²,

et al. 2017

Eur J of Neuroscience

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“…Cerebral cortex governs motor activity, and lesions or disorganization in the WM may promote the occurrence of motor disorders. The WM like corpus callosum is composed of nerve tracts consisting of myelinated axons, which link different parts of the brain and transmit nervous influx between neurons [37] . WM lesions also hinder the neurotransmission between cerebral structures [38] .…”

Section: Discussionmentioning

confidence: 99%

Neonatal Lipopolysaccharide Infection Causes Demyelination and Behavioral Deficits in Adult and Senile Rat Brain

2017

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Background: Neonatal bacterial infections have been reported to cause white matter loss, although studies concerning the influence of infection on the expression of myelin and aging are still in their emerging state. Purpose: The present study aimed to investigate the effects of perinatal lipopolysaccharide (LPS) exposure on the myelination at different age points using histochemical and immunocytochemical techniques and the relative motor coordination. Methods: A rat bacterial infection model was established by exposing the neonatal rats with LPS (0.3 mg/kg body weight, i.p., on postnatal day (PND) 3 followed by a booster at PND 5) and its impact was studied on the myelination and motor coordination in young, adult, and senile rats. Results: The results obtained suggest that the administration of LPS induces demyelination, predominantly in cortex and corpus callosum. Low expression level of myelin oligodendrocyte glycoprotein (MOG) was observed at all time points, with prominence at 12, 18, and 24 months of age. In addition, reduced staining with luxol fast blue stain was also recorded in the experimentals. With the increasing demyelination and declining motor ability, LPS exposure also seemed to accelerate normal aging symptoms. Conclusion: There is a direct correlation of myelin damage and poor motor coordination with age. This would provide a better incite to understand inflammation-associated demyelinating changes in age-associated neurodegenerative disorders. Since, no long-term studies on behavioral impairments caused by LPS-induced demyelination in the central nervous system has been reported so far, this work would help in the better understanding of the long-term pathological effects of bacterial-induced demyelination.

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“…As seen in humans, certain behavioral changes can be observed in EAE mice (Acharjee et al, 2013; Franco-Pons et al, 2007; Jones et al, 2008; Legroux and Arbour, 2015; Moore et al, 2014; Serra-de-Oliveira et al, 2015; Ulrich et al, 2010; Wang et al, 2013). Clinical signs and paralysis in EAE mice are scored on a scale from 0 (clinically normal) to 5 (moribund) (Miller et al, 2010).…”

Section: Discussionmentioning

confidence: 92%

Intracranial delivery of interleukin-17A via adeno-associated virus fails to induce physical and learning disabilities and neuroinflammation in mice but improves glucose metabolism through AKT signaling pathway

Yang

Kou

Lim

et al. 2016

Brain, Behavior, and Immunity

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Interleukin-17A (IL-17A) is generally considered as one of the pathogenic factors involved in multiple sclerosis (MS). Indirect evidence for this is that IL-17A-producing T helper 17 (Th17) cells preferentially accumulate in lesions of MS and experimental autoimmune encephalomyelitis (EAE). However, a direct involvement of IL-17A in MS pathogenesis is still an open question. In this study, we overexpressed IL-17A in the brains of mice (IL-17A-in-Brain mice) via recombinant adeno-associated virus serotype 5 (rAAV5)-mediated gene delivery. In spite of high levels of IL-17A expression in the brain and blood, IL-17A-in-Brain mice exhibit no inflammatory responses and no abnormalities in motor coordination and spatial orientation. Unexpectedly, IL-17A-in-Brain mice show decreases in body weight and adipose tissue mass and an improvement in glucose tolerance and insulin sensitivity. IL-17A enhances glucose uptake in PC12 cells by activation of AKT. Our results provide direct evidence for the first time that IL-17A overexpression in the central nervous system does not cause physical and learning disabilities and neuroinflammation and suggest that IL-17A may regulate glucose metabolism through the AKT signaling pathway.

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Behavioural changes observed in demyelination model shares similarities with white matter abnormalities in humans

Cited by 36 publications

References 63 publications

miR‐219 attenuates demyelination in cuprizone‐induced demyelinated mice by regulating monocarboxylate transporter 1

miR‐219 attenuates demyelination in cuprizone‐induced demyelinated mice by regulating monocarboxylate transporter 1

Neonatal Lipopolysaccharide Infection Causes Demyelination and Behavioral Deficits in Adult and Senile Rat Brain

Intracranial delivery of interleukin-17A via adeno-associated virus fails to induce physical and learning disabilities and neuroinflammation in mice but improves glucose metabolism through AKT signaling pathway

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