老年性耳聋患者内皮祖细胞功能变化

目的探讨老年性耳聋患者外周血内皮祖细胞(EPCs)功能的变化。方法分离老年性耳聋患者(观察组)和健康老年人(对照组)外周血中单个核细胞,诱导其分化为EPCs,检测2组培养第7天的EPCs集落数目和细胞计数、黏附、增殖和迁移能力并进行比较。结果观察组EPCs集落数目(1.40±0.37)个少于对照组(2.88±0.48)个,差别有统计学意义(t=7.734,P<0.01)。观察组EPCs细胞计数(54.32±9.24)个少于对照组(67.64±8.39)个,差别有统计学意义(t=3.376,P<0.01)。与对照组相比,观察组黏附细胞数明显减少(P<0.05);EPCs增殖能力和迁移能力下降,差别均有统计学意义(P<0.01)。结论 EPCs功能下降可能为老年性耳聋的发病机制之一。     

Cognitive self-consciousness–a predictor of increased anxiety following first-time diagnosis of age-related hearing loss

This study tested prospective models of anxiety and depression following a first time diagnosis of age-related hearing loss, also known as presbycusis, which is one of the most common and disabling health problems in the world. The predictor of interest was cognitive self-consciousness (CSC; Cartwright-Hatton & Wells (1997). Beliefs about worry and intrusions: The Meta-Cognitions Questionnaire and its correlates. Journal of Anxiety Disorders, 11, 276–279.), or the tendency to closely attend to and monitor the content and process of one's own thoughts. Sixty-seven older adults were assessed at a university-based audiology clinic at three timepoints: at the time of diagnosis (T1), six (T2), and 12 months later (T3). Measures of anxiety, depression, and CSC were collected. It was hypothesized that a subset of older adults with hearing loss would report increased CSC at T2. Additionally, the interaction of CSC and anxiety and depression symptoms at T2 was expected to predict significant variance in measures of anxiety and depression at T3, even after baseline levels of distress were controlled in regression models. Finally, it was hypothesized that consistent use of a hearing aid by T3 would act as a palliative to reduce distress in response to hearing loss at T3. Results were partially consistent with hypotheses and point to a new direction in preventing anxiety and depression following a first time diagnosis of presbycusis.     

Effects of Age, Age-Related Hearing Loss, and Contralateral Cafeteria Noise on the Discrimination of Small Frequency Changes: Psychoacoustic and Electrophysiological Measures

The aim of the study was to examine central auditory processes compromised by age, age-related hearing loss, and the presentation of a distracting cafeteria noise using auditory event-related potentials (ERPs). In addition, the relation of ERPs to behavioral measures of discrimination was investigated. Three groups of subjects participated: young normal hearing, elderly subjects with normal hearing for their age, and elderly hearing-impaired subjects. Psychoacoustic frequency discrimination thresholds for a 1000-Hz pure tone were determined in quiet and in the presence of a contralateral cafeteria noise. To elicit ERPs, small frequency contrasts were presented with and without noise under unattended and attended conditions. In the attended condition, behavioral measures of d′ detectability and reaction times were also obtained. Noise affected all measures of behavioral frequency discrimination significantly. Except N1, all ERP components in the standard and difference waveforms decreased significantly in amplitude and increased in latency to the same degree in all three subject groups, arguing against a specific age-related sensitivity to the effects of contralateral background noise. For N1 amplitude, the effect of noise was different in the three subject groups, with a complex interaction of age, hearing loss, and attention. Behavioral frequency discrimination was not affected by age but deteriorated significantly in the elderly subjects with hearing loss. In the electrophysiological test, age-related changes occurred at various levels. The most prominent finding in the response to the standard stimuli was a sustained negativity (N2) following P2 in the young subjects that was absent in the elderly, possibly indicating a deficit in the inhibition of irrelevant information processing. In the attended difference waveform, significantly larger N2b and smaller P3b amplitudes and longer N2b and P3b latencies were observed in the elderly indicating different processing strategies. The pronounced age-related changes in the later cognitive components suggest that the discrimination of difficult contrasts, although behaviorally maintained, becomes more effortful in the elderly.     

Age-related changes in calbindin D-28k and calretinin immunoreactivity in the inferior colliculus of CBA/CaJ and C57Bl/6 mice

This study examines calbindin D-28k and calretinin immunoreactivity in the inferior colliculus (IC) of young and old mice of two strains. The CBA/CaJ mouse maintains good hearing until very late in life, whereas the C57Bl/6 strain exhibits severe sensorineural hearing loss at an early age. Young and old mice of both strains were selected with matching auditory brainstem response audiograms and gap detection thresholds. Brain sections were reacted with anti-calbindin D-28k (CB) and anti-calretinin (CR). Staining patterns were characterized and cell counts performed. CB immunoreactivity was high only in the nucleus of the commissure (NCO); counts revealed a 22.3% decrease in the number of CB+ cells in old CBA mice and a 25.1% decrease in old C57 mice. Calretinin immunoreactivity was high in the pericentral regions of the IC, but the central nucleus was devoid of CR+ cells. The dorsal cortex, lateral nucleus, and NCO showed increases of 42.3, 49.0, and 61%, respectively, in the number of CR+ cells, but only in the old CBA mice. No significant change was observed in the old C57 mice. Whereas decreases in CB immunoreactivity are common with age, this study is the first to report an age-related increase in CR immunoreactivity in the auditory system. The increase in CR+ cells is a possible compensatory adaptation to the decrease in CB+ cells. That the number of CR+ cells remains constant with age in C57 mice suggests this compensation may depend upon stimulus-driven activity, but this requires further study. J. Comp. Neurol. 386:92–110, 1997. © 1997 Wiley-Liss, Inc.     

Evidence for independent peripheral and central age-related hearing impairment

Deleterious age-related changes in the central auditory nervous system have been referred to as central age-related hearing impairment (ARHI) or central presbycusis. Central ARHI is often assumed to be the consequence of peripheral ARHI. However, it is possible that certain aspects of central ARHI are independent from peripheral ARHI. A confirmation of this possibility could lead to significant improvements in current rehabilitation practices. The major difficulty in addressing this issue arises from confounding factors, such as other age-related changes in both the cochlea and central non-auditory brain structures. Because gap detection is a common measure of central auditory temporal processing, and gap detection thresholds are less influenced by changes in other brain functions such as learning and memory, we investigated the potential relationship between age-related peripheral hearing loss (i.e., audiograms) and age-related changes in gap detection. Consistent with previous studies, a significant difference was found for gap detection thresholds between young and older adults. However, among older adults, no significant associations were observed between gap detection ability and several other independent variables including the pure tone audiogram average, the Wechsler Adult Intelligence Scale-Vocabulary score, gender, and age. Statistical analyses showed little or no contributions from these independent variables to gap detection thresholds. Thus, our data indicate that age-related decline in central temporal processing is largely independent of peripheral ARHI.     

Influence of genotype and age on noise-induced auditory losses

The mouse was used as a model in order to determine how genetic contributions interact with age, producing genotype-specific patterns of noise-induced auditory losses. Inbred CBA/J, AUS/sJ, and SJL/J mice were exposed to 5 min of a 124-dB octave band (12-to 24-kHz) noise at either 20, 180, or 360 days of age. in all mice, the youngest subjects were most severely affected, and the cochlear loss was most pronounced near the center frequency of the noise exposure (16 kHz). With increasing age, the maximal loss occurred at successively higher frequencies. This agerelated pattern proceeded most rapidly in the CBA/J, and most slowly in the SJL/J, genotype. The AUS/sJ strain was most adversely affected. These findings were discussed with reference to hypotheses relating genotype to susceptibility to noise-produced cochlear damage, and to industrial surveys describing ethnic differences of noise-induced hearing loss.This work was supported by Grants 5-R01-AG-01018 from the U.S. National Institute on Aging and 1-R01-NS-17201 from the U.S. National Institute of Neurological and Communicative Diseases and Stroke.     

Morphology of the dorsal cochlear nucleus in C57BL/6J and CBA/J mice across the life span.

The morphology of the dorsal cochlear nucleus (DCN) was evaluated across the life span in inbred C57BL/6J (C57) and CBA/J (CBA) mice using 5 age groups (young adult to very old). C57 mice exhibit progressive cochlear sensorineural pathology and hearing loss during middle age; CBA mice have only modest sensorineural pathology late in life. DCN layers I, II, and III were evaluated histologically with serial sections stained for Nissl and fibers. DCN volume decreased with age in C57 mice, but the change began earliest and was most pronounced in layer III. In CBA mice, volume increased during the first year of life and decreased only in the oldest mice. All major DCN cell types were found in both strains at all ages. There was an age-related decrease in the mean size of neurons in C57 mice that was first observed in layer III. In CBA mice, only a nonsignificant trend toward smaller neurons was observed in the oldest mice. An age-related decline in the number of neurons in layer III (but not in layers I and II) occurred in C57 mice. Aged CBA mice exhibited no significant loss of DCN neurons. Thus, age-related changes in the DCN were much more pronounced in C57 mice than in CBA mice, and the changes in C57 mice were most pronounced in layer III. Because layer III receives most of the DCN's primary auditory input, it would be directly affected by age-related hearing loss and degeneration of spiral ganglion cells in C57 mice. This suggests that the age-related changes observed in DCN layer III of C57 mice are affected by progressive peripheral degenerative changes; when peripheral loss is minimal (CBA mice), less substantial age-related changes are observed.     

Age-related Decline in Kv3.1b Expression in the Mouse Auditory Brainstem Correlates with Functional Deficits in the Medial Olivocochlear Efferent System

Kv3.1b channel protein is widely distributed in the mammalian auditory brainstem, but studies have focused mainly on regions critical for temporal processing, including the medial nucleus of the trapezoid body (MNTB) and anteroventral cochlear nucleus (AVCN). Because temporal processing declines with age, this study was undertaken to determine if the expression of Kv3.1b likewise declines, and if changes are specific to these nuclei. Immunocytochemistry using an anti-Kv3.1b antibody was performed, and the relative optical density of cells and neuropil was determined from CBA/CaJ mice of four age groups. Declines in expression in AVCN, MNTB, and lateral superior olive (35, 26, and 23%) were found, but changes were limited to neuropil. Interestingly, cellular optical density declines were found in superior paraolivary nucleus, ventral nucleus of the trapezoid body, and lateral nucleus of the trapezoid body (24, 29, and 26%), which comprise the medial olivocochlear (MOC) feedback system. All declines occurred by middle age (15 months old). No age-related changes were found in the remaining regions of cochlear nucleus or in the inferior colliculus. Contralateral suppression of distortion-product otoacoustic emission amplitudes of age-matched littermates also declined by middle age, suggesting a correlation between Kv3.1 expression and MOC function. In search of more direct evidence for such a correlation, Kv3.1b knockout mice were examined. Knockouts show poor MOC function as compared to +/+ and +/− genotypes. Thus, Kv3.1b expression declines in MOC neurons by middle age, and these changes appear to correlate with functional declines in efferent activity in both middle-aged CBA mice and Kv3.1b knockout mice. An erratum to this article can be found at     

Different Cellular and Genetic Basis of Noise-Related Endocochlear Potential Reduction in CBA/J and BALB/cJ Mice

The acute and permanent effects of noise exposure on the endocochlear potential (EP) and cochlear lateral wall were evaluated in BALB/cJ (BALB) inbred mice, and compared with CBA/J (CBA) and C57BL/6 (B6) mice. Two-hour exposure to broadband noise (4–45 kHz) at 110 dB SPL leads to a ~50 mV reduction in the EP in BALB and CBA, but not B6. EP reduction in BALB and CBA is reliably associated with characteristic acute cellular pathology in stria vascularis and spiral ligament. By 8 weeks after exposure, the EP in CBA mice has returned to normal. In BALBs, however, the EP remains depressed by an average ~10 mV, so that permanent EP reduction contributes to permanent threshold shifts in these mice. We recently showed that the CBA noise phenotype in part reflects the influence of a large effect quantitative trait locus on Chr. 18, termed Nirep (Ohlemiller et al., Hear Res 260:47–53, 2010b). While CBA “EP susceptibility” alleles are dominant to those in B6, examination of (B6 × BALB) F1 hybrid mice and (F1 × BALB) N2 backcross mice revealed that noise-related EP reduction and associated cell pathology in BALBs are inherited in an autosomal recessive manner, and are dependent on multiple genes. Moreover, while N2 mice formed from B6 and CBA retain strong correspondence between acute EP reduction, ligament pathology, and strial pathology, N2s formed from B6 and BALB include subsets that dissociate pathology of ligament and stria. We conclude that the genes and cascades that govern the very similar EP susceptibility phenotypes in BALB and CBA mice need not be the same. BALBs appear to carry alleles that promote more pronounced long term effects of noise on the lateral wall. Separate loci in BALBs may preferentially impact stria versus ligament.