HDAC1 Expression, Histone Deacetylation, and Protective Role of Sodium Valproate in the Rat Dorsal Root Ganglia After Sc
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HDAC1 Expression, Histone Deacetylation, and Protective Role of Sodium Valproate in the Rat Dorsal Root Ganglia After Sciatic Nerve Transection V. A. Dzreyan 1 & S. V. Rodkin 1 & M. A. Pitinova 1 & Anatoly B. Uzdensky 1 Received: 22 February 2020 / Accepted: 7 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Nerve injury is an important reason of human disability and death. We studied the role of histone deacetylation in the response of the dorsal root ganglion (DRG) cells to sciatic nerve transection. Sciatic nerve transection in the rat thigh induced overexpression of histone deacetylase 1 (HDAC1) in the ipsilateral DRG at 1–4 h after axotomy. In the DRG neurons, HDAC1 initially upregulated at 1 h but then redistributed from the nuclei to the cytoplasm at 4 h after axotomy. Histone H3 was deacetylated at 24 h after axotomy. Deacetylation of histone H4, accumulation of amyloid precursor protein, a nerve injury marker, and GAP43, an axon regeneration marker, were observed in the axotomized DRG on day 7. Neuronal injury occurred on day 7 after axotomy along with apoptosis of DRG cells, which were mostly the satellite glial cells remote from the site of sciatic nerve transection. Administration of sodium valproate significantly reduced apoptosis not only in the injured ipsilateral DRG but also in the contralateral ganglion. It also reduced the deacetylation of histones H3 and H4, prevented axotomy-induced accumulation of amyloid precursor protein, which indicated nerve injury, and overexpressed GAP-43, a nerve regeneration marker, in the axotomized DRG. Therefore, HDAC1 was involved in the axotomy-induced injury of DRG neurons and glial cells. HDAC inhibitor sodium valproate demonstrated the neuroprotective activity in the axotomized DRG. Keywords Dorsal root ganglion . Axotomy . Sciatic nerve transection . HDAC1 . Histone . Valproate
Introduction Neurotrauma is one of the main causes of human disability and death, especially for 20–50 years old men [1–4]. Unfortunately, effective agents for urgent neuroprotection are not found yet [2–4]. After axotomy-induced disruption of the neuronal membrane, deterioration of cell homeostasis, destruction of microtubules, impairment of axonal transport, and damage to intracellular organelles, the complex signaling and metabolic processes directed either to neuron death, or to survival are initiated in the neuronal cells. Some signaling proteins are transported retrogradely to the neuronal soma and stimulate transcription factors to trigger gene expression and synthesis of essential proteins, which are then transported backward to the injured axon site to restore the axon structure and promote regeneration [2, 5]. However, in the case of * Anatoly B. Uzdensky [email protected] 1
Laboratory of Molecular Neurobiology, Southern Federal University, 194/1 Stachky Ave, Rostov-on-Don 344090, Russia
heavy injury, such as axotomy, these processes may be insufficient, and neurons die [2]. In order to find neuroprotectors for neurotrauma therapy,
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