Duchenne muscular dystrophy is a lethal genetic disease characterised by progressive degeneration of skeletal muscles induced by deficiency of dystrophin, a cytoskeletal protein expressed in myocytes and in certain neuron populations. The severity of the neurological disorder varies in humans and animal models owing to dysfunction in numerous brain areas, including the hippocampus. Cyclic treatments with high-dose glucocorticoids remain a major pharmacological approach for treating the disease; however, elevated systemic levels of either stressinduced or exogenously administered anti-inflammatory molecules dramatically affect hippocampal activity. In this study, we analysed and compared the response of hippocampal neurons isolated from wild-type and dystrophic mdx mice to acute administration of corticosterone in vitro, without the influence of other glucocorticoidregulated processes. Our results showed that in neurons of mdx mice, both the genomic and intracellular signalling- mediated responses to corticosterone were affected compared to those in wild-type animals, evoking the characteristic response to detrimental chronic glucocorticoid exposure. Responsiveness to glucocorticoids is, therefore, another function of hippocampal neurons possibly affected by deficiency of Dp427 since embryonic development. Knowing the pivotal role of hippocampus in stress hormone signalling, attention should be paid to the effects that prolonged glucocorticoid treatments may have on this and other brain areas of DMD patients.

Cultured hippocampal neurons of dystrophic mdx mice respond differently from those of wild type mice to an acute treatment with corticosterone / Fragapane, Paola; Cosmi, Francesca; DE STEFANO, Maria Egle. - In: EXPERIMENTAL CELL RESEARCH. - ISSN 0014-4827. - 386:(2020). [10.1016/j.yexcr.2019.111715]

Cultured hippocampal neurons of dystrophic mdx mice respond differently from those of wild type mice to an acute treatment with corticosterone

Francesca Cosmi
Co-primo
;
Maria Egle De Stefano
Ultimo
2020

Abstract

Duchenne muscular dystrophy is a lethal genetic disease characterised by progressive degeneration of skeletal muscles induced by deficiency of dystrophin, a cytoskeletal protein expressed in myocytes and in certain neuron populations. The severity of the neurological disorder varies in humans and animal models owing to dysfunction in numerous brain areas, including the hippocampus. Cyclic treatments with high-dose glucocorticoids remain a major pharmacological approach for treating the disease; however, elevated systemic levels of either stressinduced or exogenously administered anti-inflammatory molecules dramatically affect hippocampal activity. In this study, we analysed and compared the response of hippocampal neurons isolated from wild-type and dystrophic mdx mice to acute administration of corticosterone in vitro, without the influence of other glucocorticoidregulated processes. Our results showed that in neurons of mdx mice, both the genomic and intracellular signalling- mediated responses to corticosterone were affected compared to those in wild-type animals, evoking the characteristic response to detrimental chronic glucocorticoid exposure. Responsiveness to glucocorticoids is, therefore, another function of hippocampal neurons possibly affected by deficiency of Dp427 since embryonic development. Knowing the pivotal role of hippocampus in stress hormone signalling, attention should be paid to the effects that prolonged glucocorticoid treatments may have on this and other brain areas of DMD patients.
2020
Duchenne muscular dystrophy; glucocorticoid receptors; Hippocampus; mdx mice; stress hormones
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Cultured hippocampal neurons of dystrophic mdx mice respond differently from those of wild type mice to an acute treatment with corticosterone / Fragapane, Paola; Cosmi, Francesca; DE STEFANO, Maria Egle. - In: EXPERIMENTAL CELL RESEARCH. - ISSN 0014-4827. - 386:(2020). [10.1016/j.yexcr.2019.111715]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1335594
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