β-Actin and γ-Actin Are Each Dispensable for Auditory Hair Cell Development But Required for Stereocilia Maintenance

Hair cell stereocilia structure depends on actin filaments composed of cytoplasmic β-actin and γ-actin isoforms. Mutations in either gene can lead to progressive hearing loss in humans. Since β-actin and γ-actin isoforms are 99% identical at the protein level, it is unclear whether each isoform has distinct cellular roles. Here, we compared the functions of β-actin and γ-actin in stereocilia formation and maintenance by generating mice conditionally knocked out for Actb or Actg1 in hair cells. We found that, although cytoplasmic actin is necessary, neither β-actin nor γ-actin is required for normal stereocilia development or auditory function in young animals. However, aging mice with β-actin– or γ-actin–deficient hair cells develop different patterns of progressive hearing loss and distinct pathogenic changes in stereocilia morphology, despite colocalization of the actin isoforms. These results demonstrate overlapping developmental roles but unique post-developmental functions for β-actin and γ-actin in maintaining hair cell stereocilia

Insights Into Elevated Distortion Product Otoacoustic Emissions In Sickle Cell Disease: Comparisons of Hydroxyurea-treated and Non-treated Young Children

Distortion product otoacoustic emissions (DPOAEs) were examined in 15 normal- hearing African-American children between the ages of 6 and 14 years with homozygous sickle cell disease (SCD), who were on a regimen of hydroxyurea (HDU), a drug that reduces inflammatory processes and symptoms of SCD; a matched group of 15 African- American children with homozygous SCD not on HDU; and 15 African-American children with normal hemoglobin. DPOAEs were evoked by 13 primary tone pairs with f2 frequencies ranging from 1000 to 4500 Hz. Increased DPOAE amplitudes, believed to be a precursor of eventual hearing loss, were evident in children with SCD who were not receiving HDU. Those taking HDU had DPOAE amplitudes similar to normal controls. These findings suggest that HDU, in addition to reducing symptoms of SCD, may play a role in inhibiting or preventing cochlear pathology and hearing loss in individuals with SCD. Key Words: distortion product otoacoustic emissions; sickle cell disease; hydroxyurea Abbreviations: ABR = auditory brainstem response; DPOAE = distortion product otoacoustic emission; HDU = hydroxyurea; HbSS = homozygous sickle cell disease; ICAM = intercellular adhesion molecule; M = mean; OAE = otoacoustic emission; p = probability; PECAM = platelet-endothelial cell adhesion molecule SCD = sickle cell disease; SD = standard deviation of the mean; SOAE = spontaneous otoacoustic emission; TEOAE = transient evoked otoacoustic emission; VCAM = vascular cell adhesion molecule

Defining the Cellular Environment in the Organ of Corti following Extensive Hair Cell Loss: A Basis for Future Sensory Cell Replacement in the Cochlea

Background: Following the loss of hair cells from the mammalian cochlea, the sensory epithelium repairs to close the lesions but no new hair cells arise and hearing impairment ensues. For any cell replacement strategy to be successful, the cellular environment of the injured tissue has to be able to nurture new hair cells. This study defines characteristics of the auditory sensory epithelium after hair cell loss. Methodology/Principal Findings: Studies were conducted in C57BL/6 and CBA/Ca mice. Treatment with an aminoglycoside-diuretic combination produced loss of all outer hair cells within 48 hours in both strains. The subsequent progressive tissue re-organisation was examined using immunohistochemistry and electron microscopy. There was no evidence of significant de-differentiation of the specialised columnar supporting cells. Kir4.1 was down regulated but KCC4, GLAST, microtubule bundles, connexin expression patterns and pathways of intercellular communication were retained. The columnar supporting cells became covered with non-specialised cells migrating from the outermost region of the organ of Corti. Eventually non-specialised, flat cells replaced the columnar epithelium. Flat epithelium developed in distributed patches interrupting regions of columnar epithelium formed of differentiated supporting cells. Formation of the flat epithelium was initiated within a few weeks post-treatment in C57BL/6 mice but not for several months in CBA/Ca’s, suggesting genetic background influences the rate of re-organisation

Structure and Function of the Hair Cell Ribbon Synapse

Faithful information transfer at the hair cell afferent synapse requires synaptic transmission to be both reliable and temporally precise. The release of neurotransmitter must exhibit both rapid on and off kinetics to accurately follow acoustic stimuli with a periodicity of 1 ms or less. To ensure such remarkable temporal fidelity, the cochlear hair cell afferent synapse undoubtedly relies on unique cellular and molecular specializations. While the electron microscopy hallmark of the hair cell afferent synapse — the electron-dense synaptic ribbon or synaptic body — has been recognized for decades, dissection of the synapse’s molecular make-up has only just begun. Recent cell physiology studies have added important insights into the synaptic mechanisms underlying fidelity and reliability of sound coding. The presence of the synaptic ribbon links afferent synapses of cochlear and vestibular hair cells to photoreceptors and bipolar neurons of the retina. This review focuses on major advances in understanding the hair cell afferent synapse molecular anatomy and function that have been achieved during the past years

Self-stigma and quality of life in patients with depressive disorder: a cross-sectional study

Michaela Holubova,1,2 Jan Prasko,1 Marie Ociskova,1 Marketa Marackova,1 Ales Grambal,1 Milos Slepecky3 1Department of Psychiatry, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, Olomouc, 2Department of Psychiatry, Hospital Liberec, Liberec, Czech Republic; 3Department of Psychology Sciences, Faculty of Social Science and Health Care, Constantine the Philosopher University, Nitra, Slovak Republic Background: Self-stigma is a maladaptive psychosocial phenomenon that can affect many areas of patients’ lives and have a negative impact on their quality of life (QoL). This study explored the association between self-stigma, QoL, demographic data, and the severity of symptoms in patients with depressive disorder. Patients and methods: Patients who met the International Classification of Diseases, 10th revision, research criteria for depressive disorder were enrolled in this cross-sectional study. All outpatients completed the following measurements: the Quality of Life Enjoyment and Satisfaction Questionnaire, the Internalized Stigma of Mental Illness Scale, demographic questionnaire, and the objective and subjective Clinical Global Impression-Severity scales that measure the severity of disorder. A total of 81 depressive disorder patients (with persistent affective disorder – dysthymia, major depressive disorder, or recurrent depressive disorder) and 43 healthy controls participated in this study. Results: Compared with the healthy control group, a lower QoL was observed in patients with depressive disorder. The level of self-stigma correlated positively with total symptom severity score and negatively with QoL. Multiple regression analysis revealed that the overall rating of objective symptom severity and score of self-stigma were significantly associated with QoL. Conclusion: This study suggests a lower QoL in patients with depressive disorder in comparison with healthy controls and a negative impact of self-stigma level on QoL in patients suffering from depressive disorders. Keywords: self-stigma, quality of life, depressive disorde

The differences between patients with panic disorder and healthy controls in psychophysiological stress profile

Antonia Kotianova,1,2 Michal Kotian,2 Milos Slepecky,1,2 Michaela Chupacova,2 Jan Prasko,1,3 Ingrid Tonhajzerova4,51Department of Psychology Sciences, Faculty of Social Science and Health Care, Constantine the Philosopher University in Nitra, Nitra, Slovak Republic; 2Psychagogia, Garbiarska, Liptovsky Mikulas, Slovak Republic; 3Department of Psychiatry, Faculty of Medicine and Dentistry, University Palacky Olomouc, University Hospital, Olomouc, Czech Republic; 4Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic; 5Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak RepublicBackground: Alarming somatic symptoms, in particular, cardiovascular symptoms, are the characteristic feature of panic attacks. Increased cardiac mortality and morbidity have been found in these patients. Power spectral analysis of electrocardiogram R–R intervals is known to be a particularly successful tool in the detection of autonomic instabilities in various clinical disorders. Our study aimed to compare patients with panic disorder and healthy controls in heart rate variation (HRV) parameters (very-low-frequency [VLF], low-frequency [LF], and high-frequency [HF] band components of R–R interval) in baseline and during the response to the mental task.Subjects and methods: We assessed psychophysiological variables in 33 patients with panic disorder (10 men, 23 women; mean age 35.9±10.7 years) and 33 age- and gender-matched healthy controls (10 men, 23 women; mean age 35.8±12.1 years). Patients were treatment naïve. Heart rate, blood pressure, muscle tension, and HRV in basal conditions and after the psychological task were assessed. Power spectrum was computed for VLF (0.003–0.04 Hz), LF (0.04–0.15 Hz), and HF (0.15–0.40 Hz) bands using fast Fourier transformation.Results: In the baseline period, the VLF band was significantly lower in panic disorder group compared to controls (p<0.005). In the period of mental task, the LF/HF ratio was significantly higher in panic disorder patients compared to controls (p<0.05). No significant differences were found in the remaining parameters. There was a significant difference in ΔHF and ΔLF/HF ratio between patients and controls, with Δ increasing in patients and decreasing in controls.Conclusion: These findings revealed that patients suffering from panic disorder were characterized by relative sympathetic dominance (reactivity) in response to mental stress compared with healthy controls. Keywords: panic disorder, heart rate variability, pulse, blood pressure, muscle tension, psychological tas