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N-acetylcysteine alters apoptotic gene expression in axotomised primary sensory afferent subpopulations.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
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2009 (English)In: Neuroscience research, ISSN 0168-0102, E-ISSN 1872-8111, Vol. 65, no 2, 148-155 p.Article in journal (Refereed) Published
Abstract [en]

Novel approaches are required in peripheral nerve injury management because current surgical techniques, which do not address axotomy-induced neuronal death, lead to deficient sensory recovery. Sensory neuronal death has functional preference with cutaneous neurons dying in great numbers whilst muscle afferents survive axotomy. This offers the potential of comparing similar cell types that suffer distinct fates upon nerve injury. Here, a novel approach, combining in vivo rat nerve injury model with laser microdissection and quantitative real-time polymerase chain reaction, identifies crucial disparities in apoptotic gene expression attributable to subpopulations of differing sensory modalities and examines the response to N-acetylcysteine (NAC) therapy. We show that axotomised muscle afferent neurons survive injury due to a neuroprotective response which markedly downregulates Bax and caspase-3 mRNA. In contrast, axotomised cutaneous sensory neurons significantly upregulate caspase-3 and alter both Bcl-2 and Bax expression such that pro-apoptotic Bax predominates. N-Acetylcysteine (NAC) intervention promotes neuroprotection of cutaneous sensory neurons through considerable upregulation of Bcl-2 and downregulation of both Bax and caspase-3 mRNA. The data presented identifies differential activation of apoptotic genes in axotomised neuronal subpopulations. Furthermore, NAC therapy instigates apoptotic gene expression changes in axotomised neurons, thereby offering pharmacotherapeutic potential in the clinical treatment of nerve injury.

Place, publisher, year, edition, pages
2009. Vol. 65, no 2, 148-155 p.
Keyword [en]
Peripheral nerve injury, Dorsal root ganglion, Neuronal apoptosis, Neuroprotection, Rat
National Category
Surgery
Identifiers
URN: urn:nbn:se:umu:diva-32017DOI: 10.1016/j.neures.2009.06.008PubMedID: 19559059OAI: oai:DiVA.org:umu-32017DiVA: diva2:301283
Available from: 2010-03-03 Created: 2010-02-26 Last updated: 2017-12-12Bibliographically approved

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