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      The potential role of epigenetic modulations in BPPV maneuver exercises

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          Abstract

          Benign paroxysmal positional vertigo (BPPV) is one of the most common complaints encountered in clinics and is strongly correlated with advanced age or, possibly, degeneration. Redistribution exercises are the most effective approaches to treat BPPV, and canalith repositioning procedure (CRP) cure most BPPV cases. However, the mechanisms through which the treatment modulates systemic molecules in BPPV patients remain largely unknown. In this study, we report that the miR-34a and Sirtuin 1 (SIRT1) genes correlated with the treatment effects of CRP in BPPV subjects. We found that miR-34a expression was largely inhibited and SIRT1 expression was significantly reversed after BPPV maneuver treatment. We also confirmed that the PPAR-γ, PGC-1 and FoxO gene expressions were decreased immediately after canalith repositioning procedure (CRP) for BPPV, and were largely increased after a complete cure of BPPV. Moreover, we observed that after a complete recovery of BPPV, the ROS concentrations, pro-inflammatory cytokine concentrations and p53 expression levels were attenuated. We conclude that BPPV treatment might involve some epigenetic regulations through the mediation of miR-34a, SIRT1 functions and repression of redox status.

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          Most cited references53

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          Gene regulation and DNA damage in the ageing human brain.

          The ageing of the human brain is a cause of cognitive decline in the elderly and the major risk factor for Alzheimer's disease. The time in life when brain ageing begins is undefined. Here we show that transcriptional profiling of the human frontal cortex from individuals ranging from 26 to 106 years of age defines a set of genes with reduced expression after age 40. These genes play central roles in synaptic plasticity, vesicular transport and mitochondrial function. This is followed by induction of stress response, antioxidant and DNA repair genes. DNA damage is markedly increased in the promoters of genes with reduced expression in the aged cortex. Moreover, these gene promoters are selectively damaged by oxidative stress in cultured human neurons, and show reduced base-excision DNA repair. Thus, DNA damage may reduce the expression of selectively vulnerable genes involved in learning, memory and neuronal survival, initiating a programme of brain ageing that starts early in adult life.
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            Epidemiology of benign paroxysmal positional vertigo: a population based study.

            To examine the prevalence and incidence, clinical presentation, societal impact and comorbid conditions of benign paroxysmal positional vertigo (BPPV) in the general population. Cross-sectional, nationally representative neurotological survey of the general adult population in Germany with a two stage sampling design: screening of 4869 participants from the German National Telephone Health Interview Survey 2003 (response rate 52%) for moderate or severe dizziness or vertigo, followed by validated neurotological interviews (n = 1003; response rate 87%). Diagnostic criteria for BPPV were at least five attacks of vestibular vertigo lasting <1 min without concomitant neurological symptoms and invariably provoked by typical changes in head position. In a concurrent validation study (n = 61) conducted in two specialised dizziness clinics, BPPV was detected by our telephone interview with a specificity of 92% and a sensitivity of 88% (positive predictive value 88%, negative predictive value 92%). BPPV accounted for 8% of individuals with moderate or severe dizziness/vertigo. The lifetime prevalence of BPPV was 2.4%, the 1 year prevalence was 1.6% and the 1 year incidence was 0.6%. The median duration of an episode was 2 weeks. In 86% of affected individuals, BPPV led to medical consultation, interruption of daily activities or sick leave. In total, only 8% of affected participants received effective treatment. On multivariate analysis, age, migraine, hypertension, hyperlipidaemia and stroke were independently associated with BPPV. BPPV is a common vestibular disorder leading to significant morbidity, psychosocial impact and medical costs.
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              Duration of nuclear NF-kappaB action regulated by reversible acetylation.

              The nuclear expression and action of the nuclear factor kappa B (NF-kappaB) transcription factor requires signal-coupled phosphorylation and degradation of the IkappaB inhibitors, which normally bind and sequester this pleiotropically active factor in the cytoplasm. The subsequent molecular events that regulate the termination of nuclear NF-kappaB action remain poorly defined, although the activation of de novo IkappaBalpha gene expression by NF-kappaB likely plays a key role. Our studies now demonstrate that the RelA subunit of NF-kappaB is subject to inducible acetylation and that acetylated forms of RelA interact weakly, if at all, with IkappaBalpha. Acetylated RelA is subsequently deacetylated through a specific interaction with histone deacetylase 3 (HDAC3). This deacetylation reaction promotes effective binding to IkappaBalpha and leads in turn to IkappaBalpha-dependent nuclear export of the complex through a chromosomal region maintenance-1 (CRM-1)-dependent pathway. Deacetylation of RelA by HDAC3 thus acts as an intranuclear molecular switch that both controls the duration of the NF-kappaB transcriptional response and contributes to the replenishment of the depleted cytoplasmic pool of latent NF-kappaB-IkappaBalpha complexes.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                14 June 2016
                18 May 2016
                : 7
                : 24
                : 35522-35534
                Affiliations
                1 Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan
                2 Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei, Taiwan
                3 Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
                4 Department of Sports Sciences, University of Taipei, Taipei, Taiwan
                5 Department of Physical Medicine and Rehabilitation, Taichung Veterans General Hospital, Taichung, Taiwan
                6 Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
                7 Department of Physical Medicine and Rehabilitation, School of Medicine National Yang-Ming University, Taipei, Taiwan
                Author notes
                Correspondence to: Chung-Lan Kao, clkao@ 123456vghtpe.gov.tw
                Article
                9446
                10.18632/oncotarget.9446
                5094942
                27203679
                8e1c06a8-a127-4a64-9f10-7c44ed0224e3
                Copyright: © 2016 Tsai et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 4 March 2016
                : 10 May 2016
                Categories
                Research Paper: Gerotarget (Focus on Aging)

                Oncology & Radiotherapy
                benign paroxysmal positional vertigo,microrna,sirtuin 1,maneuver exercises,gerotarget

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