Developmental Neurotoxicity of Toluene in Rats as Measured by L‐Ornithine Decarboxylase in Cerebellum

Nielsen, Brian S.; Lam, Henrik Rye; Ladefoged, Ole

doi:10.1034/j.1600-0773.2003.920109.x

Cited by 2 publications

(1 citation statement)

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“…The damage to the cerebellar cortex, especially in the number of granule neurons and the thickness of EGL, was more severe in zincdeficient pups than in undernourished pair-fed pups. Toxic compounds are also known to damage the cerebellum during development (Antonio et al, 2002;Nielsen et al, 2003;Stoltenburg-Didinger et al, 1990). In rodents, in vitro and in vivo exposure of the cerebellum to methylmerucy, an animal model for Minamata disease, causes a severe decrease in the number of migrating granule neurons as seen in our study (Howard and Mottet, 1986;Kunimoto and Suzuki, 1997;Sager et al, 1982).…”

Section: Genetic Manipulations Of the Expression Of Mmps Provided Ampsupporting

confidence: 65%

On the contribution of MMP-2 and MMP-9 to the postnatal cerebellar corticogenesis

Ayoub¹

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On the Contribution of MMP-2 and MMP-9 to the Postnatal Cerebellar Corticogenesis Albert E. Ayoub The development of the cerebellar cortex is dependent on orchestrated cell-cell, cell-matrix interactions, as well as intrinsic genetic programs. Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade ECM molecules and are involved in neuronal migration, process extension, and synaptic plasticity. The current study investigated (1) the developmental expression and activity of MMP-2 and MMP-9, and (2) the effect of blocking the activity of MMP-2 and MMP-9 by a specific inhibitor on the histogenesis of the cerebellar cortex. Cerebella were collected from rat pups every three days starting at postnatal day 3 (P3) until P25-a period equivalent to the third gestational trimester in humans. Temporal analysis of MMP activity by gelatinase assay showed that both the active and latent forms were present in the developing cerebellum. The mRNA analysis by real-time quantitative PCR indicated that the expression pattern of MMP-2 and MMP-9 mRNA agreed with their gelatinase activity. In situ zymography was localized in the EGL, the PCL, and IGL. The EGL, Bergamnn glial fibers, and the PCL showed immunoreactivity for MMP-2, whereas MMP-9 immunoreactivity was detected only in PC and the EGL. Exposure of organotypic slices to a specific MMP-2/MMP-9 inhibitor (1.6, 3.2 or 6.4 µM) altered the activity of MMP-2 and 9 and caused a significant increase in the thickness of the EGL, and a decrease in migrating granule neurons in the molecular layer. Our study suggests that MMP-2 and MMP-9 play a role in the postnatal cerebellar histogenesis.

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Section: Genetic Manipulations Of the Expression Of Mmps Provided Ampsupporting

confidence: 65%

On the contribution of MMP-2 and MMP-9 to the postnatal cerebellar corticogenesis

Ayoub¹

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Developmental neurotoxicity – Challenges in the 21st Century and In Vitro Opportunities

Smirnova

2014

ALTEX

102

139

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Summary In recent years neurodevelopmental problems in children have increased at a rate that suggests lifestyle factors and chemical exposures as likely contributors. When environmental chemicals contribute to neurodevelopmental disorders developmental neurotoxicity (DNT) becomes an enormous concern. But how can it be tackled? Current animal test-based guidelines are prohibitively expensive, at $1.4 million per substance, while their predictivity for human health effects may be limited, and mechanistic data that would help species extrapolation are not available. A broader screening for substances of concern requires a reliable testing strategy, applicable to larger numbers of substances, and sufficiently predictive to warrant further testing. This review discusses the evidence for possible contributions of environmental chemicals to DNT, limitations of the current test paradigm, emerging concepts and technologies pertinent to in vitro DNT testing and assay evaluation, as well as the prospect of a paradigm shift based on 21st century technologies.

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Developmental Neurotoxicity of Toluene in Rats as Measured by L‐Ornithine Decarboxylase in Cerebellum

Cited by 2 publications

References 15 publications

On the contribution of MMP-2 and MMP-9 to the postnatal cerebellar corticogenesis

On the contribution of MMP-2 and MMP-9 to the postnatal cerebellar corticogenesis

Developmental neurotoxicity – Challenges in the 21st Century and In Vitro Opportunities

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