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Open AccessArticle

Deregulated miR-29b-3p Correlates with Tissue-Specific Activation of Intrinsic Apoptosis in An Animal Model of Amyotrophic Lateral Sclerosis

1
Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Cytology, 44801 Bochum, Germany
2
Ruhr University Bochum, Clinical Research Center, Department of Molecular Gastrointestinal Oncology, 44801 Bochum, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper and share the senior authorship.
Cells 2019, 8(9), 1077; https://doi.org/10.3390/cells8091077
Received: 12 August 2019 / Revised: 6 September 2019 / Accepted: 11 September 2019 / Published: 12 September 2019
(This article belongs to the Special Issue Key Signalling Molecules in Aging and Neurodegeneration)
Amyotrophic lateral sclerosis (ALS) is one of the most common incurable motor neuron disorders in adults. The majority of all ALS cases occur sporadically (sALS). Symptoms of ALS are caused by a progressive degeneration of motor neurons located in the motor cortex and spinal cord. The question arises why motor neurons selectively degenerate in ALS, while other cells and systems appear to be spared the disease. Members of the intrinsic apoptotic pathway are frequent targets of altered microRNA expression. Therefore, microRNAs and their effects on cell survival are subject of controversial debates. In this study, we investigated the expression of numerous members of the intrinsic apoptotic cascade by qPCR, western blot, and immunostaining in two different regions of the CNS of wobbler mice. Further we addressed the expression of miR-29b-3p targeting BMF, Bax, and, Bak, members of the apoptotic pathway. We show a tissue-specific differential expression of BMF, Bax, and cleaved-Caspase 3 in wobbler mice. An opposing regulation of miR-29b-3p expression in the cerebellum and cervical spinal cord of wobbler mice suggests different mechanisms regulating the intrinsic apoptotic pathway. Based on our findings, it could be speculated that miR-29b-3p might regulate antiapoptotic survival mechanisms in CNS areas that are not affected by neurodegeneration in the wobbler mouse ALS model. View Full-Text
Keywords: ALS; wobbler mouse; apoptosis; microRNA; neurodegeneration; cerebellum; spinal cord; motor neuron disease ALS; wobbler mouse; apoptosis; microRNA; neurodegeneration; cerebellum; spinal cord; motor neuron disease
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Klatt, C.L.; Theis, V.; Hahn, S.; Theiss, C.; Matschke, V. Deregulated miR-29b-3p Correlates with Tissue-Specific Activation of Intrinsic Apoptosis in An Animal Model of Amyotrophic Lateral Sclerosis. Cells 2019, 8, 1077.

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