The Expression of E2F1, p53, and Caspase 3 in the Rat Dorsal Root Ganglia After Sciatic Nerve Transection
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The Expression of E2F1, p53, and Caspase 3 in the Rat Dorsal Root Ganglia After Sciatic Nerve Transection Valentina Dzreyan 1 & Stanislav Rodkin 1 & Viktor Nikul 1 & Maria Pitinova 1 & Anatoly Uzdensky 1 Received: 20 July 2020 / Accepted: 7 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Neurotrauma is among the main causes of human disability and mortality. Nerve injury impairs not only neurons but also causes death of satellite glial cells remote from the injury site. We studied the dynamics of expression of different proapoptotic proteins (E2F1, p53, caspase 3) in the dorsal root ganglia (DRG) of a rat after sciatic nerve transection. TUNEL staining and immunoblotting were used for analysis of cell apoptosis and axotomy-induced biochemical changes. Apoptosis of glial cells was observed at 24 h after sciatic nerve transection and increased on day 7, when apoptosis of some neurons only started. The earliest proapoptotic event in the injured DRG was overexpression of transcription factor E2F1 at 4 h after sciatic nerve transection. This preceded the induction of p53 and cleavage of caspase 3 at 24-h post-axotomy. The nerve injury marker amyloid precursor protein and the nerve regeneration marker GAP-43 were overexpressed in DRG on day 7 after sciatic nerve transection. We also developed a novel fluorescence method for differential visualization of the rat DRG and nerves by means of double staining with propidium iodide and Hoechst 33342 that impart red and blue-green fluorescence, respectively. The present experiments showed that glial cells remote from the nerve transection site were more vulnerable to axotomy than DRG neurons. E2F1 and p53 may be considered promising molecular targets for development of potential neuroprotective agents. Keywords Dorsal root ganglion . Nerve injury . Satellite glia . Apoptosis . Nerve and ganglion visualization
Introduction Neurotrauma is among the main causes of human disability and mortality, especially for young and middle age men. Peripheral nerve injury accounts about 10% cases of neurotrauma. Unfortunately, clinically effective neuroprotectors that can rescue the damaged neurons are absent yet (Hill 2016; Laskowitz and Grant 2016; Witiw and Fehlings 2015). In the central nervous system, the injured neurons do not regenerate and die. However, in the peripheral nervous system, a significant fraction of motor and sensory neurons (about 30%) survive axotomy, regenerate, and restore nerve connections (Dubový et al. 2018; Hill 2016; Patodia and Raivich 2012; Rishal and Fainzilber 2014). Severe nerve injury such as complete nerve transection, i.e., axotomy leads to either necrosis or apoptosis. The previous studies showed that dozens of cellular proteins are up- or downregulated in the axotomized neurons of invertebrate and vertebrate animals * Anatoly Uzdensky [email protected] 1
Laboratory of Molecular Neurobiology, Southern Federal University, 194/1 Stachky Ave., Rostov-on-Don, Russia 344090
(Casas et al. 2015; Demyanenko et al. 2019
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