No effects of mobile phone electromagnetic field on auditory brainstem response

The present study investigated the possible effects of the electromagnetic field (EMF) emitted by an ordinary GSM mobile phone (902.4 MHz pulsed at 217 Hz) on brainstem auditory processing. Auditory brainstem responses (ABR) were recorded in 17 healthy young adults, without a mobile phone at baseline, and then with a mobile phone on the ear under EMF‐off and EMF‐on conditions. The amplitudes, latencies, and interwave intervals of the main ABR components (waves I, III, V) were compared among the three conditions. ABR waveforms showed no significant differences due to exposure, suggesting that short‐term exposure to mobile phone EMF did not affect the transmission of sensory stimuli from the cochlea up to the midbrain along the auditory nerve and brainstem auditory pathways. Bioelectromagnetics 31:48–55, 2010. © 2009 Wiley‐Liss, Inc.     

Photobiomodulation using low‐level 808 nm diode laser rescues cochlear synaptopathy after acoustic overexposure in rat

A certain degree of noise can cause hearing problems without a permanent change in the hearing threshold, which is called hidden hearing loss and results from partial loss of auditory synapses. Photobiomodulation (PBM) enhances neural growth and connections in the peripheral nervous systems. In this study, we assessed whether PBM could rescue cochlear synaptopathy after acoustic overexposure in rat. PBM was performed for 7 days after noise exposure. The auditory brainstem responses (ABRs) were acquired before and after noise exposure using a tone and a paired‐click stimulus. Auditory response to paired click sound with short time interval was performed to evaluate auditory temporal processing ability. In the result, hearing threshold recovered 2 weeks after noise exposure in both groups. Peak wave 1 amplitude of the ABR and ABR recovery threshold did not recover in the noise only group, whereas it fully recovered in the noise + PBM group. The number of synaptic ribbons was significantly different in the control and noise only groups, while there was no difference between the control and noise + PBM group. These results indicate that PBM rescued peak wave 1 amplitude and maintained the auditory temporal processing ability resulting from a loss of synaptic ribbons after acoustic overexposure.     

Identifying the Threshold of Iron Deficiency in the Central Nervous System of the Rat by the Auditory Brainstem Response

The deleterious effects of anemia on auditory nerve (AN) development have been well investigated; however, we have previously reported that significant functional consequences in the auditory brainstem response (ABR) can also occur as a consequence of marginal iron deficiency (ID). As the ABR has widespread clinical use, we evaluated the ability of this electrophysiological method to characterize the threshold of tissue ID in rats by examining the relationship between markers of tissue ID and severity of ABR latency defects. To generate various levels of ID, female Long-Evans rats were exposed to diets containing sufficient, borderline, or deficient iron (Fe) concentrations throughout gestation and offspring lifetime. We measured hematological indices of whole body iron stores in dams and offspring to assess the degree of ID. Progression of AN ID in the offspring was measured as ferritin protein levels at different times during postnatal development to complement ABR functional measurements. The severity of ABR deficits correlated with the level of Fe restriction in each diet. The sufficient Fe diet did not induce AN ID and consequently did not show an impaired ABR latency response. The borderline Fe diet, which depleted AN Fe stores but did not cause systemic anemia resulted in significantly increased ABR latency isolated to Peak I.The low Fe diet, which induced anemia and growth retardation, significantly increased ABR latencies of Peaks I to IV. Our findings indicate that changes in the ABR could be related to various degrees of ID experienced throughout development.     

Calpain 1在水杨酸钠诱导耳鸣大鼠的下丘脑神经元中的表达及对听力的影响

为了考察Calpain 1在水杨酸钠诱导耳鸣大鼠的下丘脑神经元中的表达及对听力的影响,本研究通过腹腔注射水杨酸钠建立耳鸣大鼠模型,并腹腔注射钙蛋白酶抑制剂ALLN来处理大鼠。听性脑干反应(ABR)测试显示,水杨酸钠可显著升高大鼠的的听力阈值和Ⅰ、Ⅲ和Ⅴ波潜伏期、Ⅰ~Ⅴ和Ⅲ~Ⅴ波间潜伏期,而钙蛋白酶抑制剂可明显抑制这种变化。免疫组化、RT-PCR和Western blotting检测结果均显示,水杨酸钠可明显上调大鼠下丘组织中Calpain 1的表达,而钙蛋白酶抑制剂可显著抑制Calpain 1的上调。此外,钙蛋白酶抑制剂可显著抑制水杨酸钠诱导的大鼠下丘组织中NMDA受体亚型NR2A的上调。水杨酸钠上调了大鼠耳蜗核组织中炎症因子TNF-α、IL-1β和IL-6的表达,而钙蛋白酶抑制剂可显著抑制炎症因子的表达。本研究提示,水杨酸钠可损伤大鼠的听觉功能,上调Calpain 1、NMDA受体和促炎细胞因子的表达。钙蛋白酶抑制剂可显著改善大鼠的听觉功能,其机制与抑制Calpain 1、NMDA受体和促炎细胞因子的表达有关。     

Reduced acoustic startle response and peripheral hearing loss in the 5xFAD mouse model of Alzheimer's disease

Hearing dysfunction has been associated with Alzheimer's disease (AD) in humans, but there is little data on the auditory function of mouse models of AD. Furthermore, characterization of hearing ability in mouse models is needed to ensure that tests of cognition that use auditory stimuli are not confounded by hearing dysfunction. Therefore, we assessed acoustic startle response and pre‐pulse inhibition in the double transgenic 5xFAD mouse model of AD from 3–4 to 16 months of age. The 5xFAD mice showed an age‐related decline in acoustic startle as early as 3–4 months of age. We subsequently tested auditory brainstem response (ABR) thresholds at 4 and 13–14 months of age using tone bursts at frequencies of 2–32 kHz. The 5xFAD mice showed increased ABR thresholds for tone bursts between 8 and 32 kHz at 13–14 months of age. Finally, cochleae were extracted and basilar membranes were dissected to count hair cell loss across the cochlea. The 5xFAD mice showed significantly greater loss of both inner and outer hair cells at the apical and basal ends of the basilar membrane than wild‐type mice at 15–16 months of age. These results indicate that the 5xFAD mouse model of AD shows age‐related decreases in acoustic startle responses, which are at least partially due to age‐related peripheral hearing loss. Therefore, we caution against the use of cognitive tests that rely on audition in 5xFAD mice over 3–4 months of age, without first confirming that performance is not confounded by hearing dysfunction.     

急性低氧时豚鼠声信号传入的变化

本工作的目的是研究急性高原低氧对豚鼠听觉传入功能的影响。２０只豚鼠分为４组,分别接受模拟海拔高度为５０００、６０００、７０００和８００ｏｍ的急性低氧暴露,于不同时间测定听觉脑干诱发反应各波的潜伏期、峰间期、振幅和ＩＩＩ波的电反应阈（听阈）。结果如下：当升至预定的海拔高度和在低氧维持阶段,６０００ｍ以上组各波潜伏期延长,其中ＩＩ波变化更明显;回到海平面高度后逐渐恢复,１ｈ内基本可恢复正常;潜伏期变化的程度与海拔高度有关。在低氧阶段各波振幅普遍下降,回到海平面高度后逐渐回升,但恢复至正常所需时间较长。在升至预定的海拔高度和其后低氧维持阶段,各组动物的听阈均上升,脱离低氧后即可迅速恢复,１ｈ内可恢复正常。结果表明,急性高原低氧使听觉脑干传导时间延长,传入神经元兴奋性降低,听敏度下降,因而可以推测它能影响声信号的传入。     

Loss of Central Auditory Processing in a Mouse Model of Canavan Disease

Canavan Disease (CD) is a leukodystrophy caused by homozygous null mutations in the gene encoding aspartoacylase (ASPA). ASPA-deficiency is characterized by severe psychomotor retardation, and excessive levels of the ASPA substrate N-acetylaspartate (NAA). ASPA is an oligodendrocyte marker and it is believed that CD has a central etiology. However, ASPA is also expressed by Schwann cells and ASPA-deficiency in the periphery might therefore contribute to the complex CD pathology. In this study, we assessed peripheral and central auditory function in the Aspa^lacZ/lacZ rodent model of CD using auditory brainstem response (ABR). Increased ABR thresholds and the virtual loss of waveform peaks 4 and 5 from Aspa^lacZ/lacZ mice, indicated altered central auditory processing in mutant mice compared with Aspa^wt/wt controls and altered central auditory processing. Analysis of ABR latencies recorded from Aspa^lacZ/lacZ mice revealed that the speed of nerve conduction was unchanged in the peripheral part of the auditory pathway, and impaired in the CNS. Histological analyses confirmed that ASPA was expressed in oligodendrocytes and Schwann cells of the auditory system. In keeping with our physiological results, the cellular organization of the cochlea, including the organ of Corti, was preserved and the spiral ganglion nerve fibres were normal in ASPA-deficient mice. In contrast, we detected substantial hypomyelination in the central auditory system of Aspa^lacZ/lacZ mice. In summary, our data suggest that the lack of ASPA in the CNS is responsible for the observed hearing deficits, while ASPA-deficiency in the cochlear nerve fibres is tolerated both morphologically and functionally.     

Effects of antioxidants on induction of micronuclei in rat peripheral blood reticulocytes by potassium bromate.

Micronucleus induction in male F344 rat peripheral blood by potassium bromate (KBrO3), a rat renal carcinogen, and its inhibition by several antioxidants were studied using the acridine orange supravital staining method. The frequency of micronucleated reticulocytes (MNRETs) peaked 32 h after a single i.p. treatment of rats with KBrO3 at a dose of 60 mg/kg. Co-treatment with glutathione (GSH) or cysteine (Cys) i.p. at doses of 800 mg/kg and 400 mg/kg, respectively, 30 min before and 30 min after the KBrO3 treatment significantly inhibited the micronucleus induction by KBrO3. Daily i.g. administration of vitamin C for 5 days at a dose of 200 mg/kg/day was also effective in protecting against micronucleus induction by KBrO3 given on the 4th day. However, co-treatment with superoxide dismutase in liposome-encapsulated form by i.p. injection at a dose of 18,000 U/kg 30 min before and 30 min after the KBrO3 application exerted no effect. The results indicate that antioxidants, especially sulfhydryl compounds, have protective potential against the clastogenicity of KBrO3, also suggesting that active oxygen species may play an important role in its clastogenicity.     

Lead-Induced Hearing Loss in Rats and the Protective Effect of Copper

Lead is a common environmental pollutant which can induce various toxic effects to humans and/or animals. This work aimed to study the hearing loss in rats induced by lead and the protective effect of copper. The auditory brainstem response (ABR) was used to study the hearing loss in rats. The results showed that lead prolonged the latencies of wave I to V of ABRs of the rats but did not affect the interpeak latencies of waves I-III, III-V, and I-V, indicating that lead could cause hearing loss in rats by impairing the cochlea. After receiving copper, the quality and the wave latencies of the ABR of the rats were restored to a certain extent, indicating that copper played a protective role in lead-induced hearing impairment. The mechanisms were also proposed that lead could cause hearing loss in rats mainly through damaging the cochlea component, and copper might antagonize the toxicity of lead in three primary ways.     

KILLER WHALE (ORCINUS ORCA) AUDITORY EVOKED POTENTIALS TO RHYTHMIC CLICKS

Temporal auditory mechanisms were measured in killer whales ( Orcinus orca ) by recording auditory evoked potentials (AEPs) to clicks. Clicks were presented at rates from 10/sec to 1,600/sec. At low rates, clicks evoked an AEP similar to the auditory brainstem response (ABR) of other odontocetes; however, peak latencies of the main waves were 3–3.7 msec longer than in bottlenose dolphins. Fourier analysis of the ABR showed a prominent peak at 300–400 Hz and a smaller one at 800–1,200 Hz. High-rate click presentation (more than 100/sec) evoked a rate-following response (RFR). The RFR amplitude depended little on rate up to 400/sec, decreased at higher rates and became undetectable at 1,120/sec. Fourier analysis showed that RFR fundamental amplitude dependence on frequency closely resembled the ABR spectrum. The fundamental could follow clicks to around 1,000/sec, although higher harmonics of lower rates could arise at frequencies as high as 1,200 Hz. Both RFR fundamental phase dependence on frequency and the response lag after a click train indicated an RFR group delay of around 7.5 msec. This corresponds to the latency of ABR waves PIII-NIV, which indicates the RFR originates as a rhythmic, overlapping ABR sequence. The data suggest the killer whale auditory system can follow high click rates, an ability that may have been selected for as a function of high-frequency hearing and the use of rapid clicks in echolocation.     

Aroclor 1254 impairs the hearing ability of Xenopus laevis

In this study we assessed the effects of chronic, dietary exposure of Aroclor 1254 (A1254) on the hearing of Xenopus frogs. We used the auditory brainstem response (ABR) to assay changes in hearing physiology; ABR thresholds, as well as latency-intensity and amplitude-intensity profiles of the initial positive (P1) and negative (N1) peaks were measured. Two groups of animals that received 50 ppm and 100 ppm of A1254 in their diet from 5 days post-fertilization through metamorphosis were compared to a control group that received untreated chow. The results showed significant threshold elevations in the 3–4 kHz range and significantly delayed peak latencies and reduced amplitudes at these frequencies in A1254 treated animals as compared to control animals. These findings indicate that A1254 selectively damages the high-frequency sensorineural hearing system associated with the basilar papilla of frogs. This preferential damage may be related to inherent differences in the vulnerability of the basilar versus amphibian papilla in the frog. The overall results of this study are also consistent with the reported A1254-induced auditory deficits in mammals indicating that the basilar papilla of the Xenopus frog may serve as an effective model for studying the effects of A1254 on the auditory system.     

Different effects of human and porcine insulin on hypoglycemia-induced abnormalities of brainstem sensory function

Following a switch from porcine insulin (PI) to human insulin (HI), a subgroup of diabetic patients complained of unawareness of hypoglycemia. In the present study, a glucose clamp technique was used to assess changes in auditory evoked brainstem responses (ABR) during infusion of HI and PI (0.015 IU/kg/min) under conditions of euglycemia (about 5.00 mM) and of hypoglycemia (3.40 and 2.60 mM) in 9 healthy volunteers. Serum insulin and plasma glucose did not differ between HI and PI conditions. ABR components remained unchanged during the euglycemic clamp, but increased in latency during hypoglycemia in all subjects. At mean glucose levels of 2.60 mM, the increase in latency of ABR wave V ranged between 50 and 400 microseconds during PI infusion, and between 100 and 2,460 microseconds during HI infusion. Thus, compared to the PI condition, changes during HI infusion were significantly more variable (p less than 0.01) due to some subjects displaying extremely prolonged ABR latencies. These findings suggest that hypoglycemia induced by HI can be more detrimental to early sensory processing in humans as compared to PI.     

Auditory brainstem responses in Cope’s gray treefrog (Hyla chrysoscelis): effects of frequency,level, sex and size

Our knowledge of the hearing abilities of frogs and toads is largely defined by work with a few well-studied species. One way to further advance comparative work on anuran hearing would be greater use of minimally invasive electrophysiological measures, such as the auditory brainstem response (ABR). This study used the ABR evoked by tones and clicks to investigate hearing in Cope’s gray treefrog (Hyla chrysoscelis). The objectives were to characterize the effects of sound frequency, sound pressure level, and subject sex and body size on ABRs. The ABR in gray treefrogs bore striking resemblance to ABRs measured in other animals. As stimulus level increased, ABR amplitude increased and latency decreased, and for responses to tones, these effects depended on stimulus frequency. Frequency-dependent differences in ABRs were correlated with expected differences in the tuning of two sensory end organs in the anuran inner ear (the amphibian and basilar papillae). The ABR audiogram indicated two frequency regions of increased sensitivity corresponding to the expected tuning of the two papillae. Overall, there was no effect of subject size and only small effects related to subject sex. Together, these results indicate the ABR is an effective method to study audition in anurans.     

Hearing sensitivity and amplitude coding in bats are differentially shaped by echolocation calls and social calls

Differences in auditory perception between species are influenced by phylogenetic origin and the perceptual challenges imposed by the natural environment, such as detecting prey- or predator-generated sounds and communication signals. Bats are well suited for comparative studies on auditory perception since they predominantly rely on echolocation to perceive the world, while their social calls and most environmental sounds have low frequencies. We tested if hearing sensitivity and stimulus level coding in bats differ between high and low-frequency ranges by measuring auditory brainstem responses (ABRs) of 86 bats belonging to 11 species. In most species, auditory sensitivity was equally good at both high- and low-frequency ranges, while amplitude was more finely coded for higher frequency ranges. Additionally, we conducted a phylogenetic comparative analysis by combining our ABR data with published data on 27 species. Species-specific peaks in hearing sensitivity correlated with peak frequencies of echolocation calls and pup isolation calls, suggesting that changes in hearing sensitivity evolved in response to frequency changes of echolocation and social calls. Overall, our study provides the most comprehensive comparative assessment of bat hearing capacities to date and highlights the evolutionary pressures acting on their sensory perception.     

CD4 T-cell depletion prevents Lassa fever associated hearing loss in the mouse model

Lassa virus (LASV) is the causative agent of Lassa fever (LF), which presents as a lethal hemorrhagic disease in severe cases. LASV-induced hearing loss in survivors is a huge socioeconomic burden, however, the mechanism(s) leading to hearing loss is unknown. In this study, we evaluate in a mouse LF model the auditory function using auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to determine the mechanisms underlying LASV-induced hearing loss. In the process, we pioneered measures of ABR and DPOAE tests in rodents in biosafety level 4 (BSL-4) facilities. Our T cell depletion studies demonstrated that CD4 T-cells play an important role in LASV-induced hearing loss, while CD8 T-cells are critical for the pathogenicity in the acute phase of LASV infection. Results presented in this study may help to develop future countermeasures against acute disease and LASV-induced hearing loss.     

Deletion of Fmr1 Alters Function and Synaptic Inputs in the Auditory Brainstem

Fragile X Syndrome (FXS), a neurodevelopmental disorder, is the most prevalent single-gene cause of autism spectrum disorder. Autism has been associated with impaired auditory processing, abnormalities in the auditory brainstem response (ABR), and reduced cell number and size in the auditory brainstem nuclei. FXS is characterized by elevated cortical responses to sound stimuli, with some evidence for aberrant ABRs. Here, we assessed ABRs and auditory brainstem anatomy in Fmr1^-/- mice, an animal model of FXS. We found that Fmr1^-/- mice showed elevated response thresholds to both click and tone stimuli. Amplitudes of ABR responses were reduced in Fmr1^-/- mice for early peaks of the ABR. The growth of the peak I response with sound intensity was less steep in mutants that in wild type mice. In contrast, amplitudes and response growth in peaks IV and V did not differ between these groups. We did not observe differences in peak latencies or in interpeak latencies. Cell size was reduced in Fmr1^-/- mice in the ventral cochlear nucleus (VCN) and in the medial nucleus of the trapezoid body (MNTB). We quantified levels of inhibitory and excitatory synaptic inputs in these nuclei using markers for presynaptic proteins. We measured VGAT and VGLUT immunolabeling in VCN, MNTB, and the lateral superior olive (LSO). VGAT expression in MNTB was significantly greater in the Fmr1^-/- mouse than in wild type mice. Together, these observations demonstrate that FXS affects peripheral and central aspects of hearing and alters the balance of excitation and inhibition in the auditory brainstem.     

Sensorineural hearing loss as evidenced by the auditory brainstem response following prenatal cocaine exposure in the Long-Evans rat

Prenatal cocaine exposure has been associated with a variety of adverse neurological effects. Three recent studies found evidence that prenatal cocaine exposure is associated with abnormal auditory electrophysiology, suggesting abnormal processing of auditory information. The present study used the auditory brainstem response to evaluate the effects of prenatal cocaine exposure on hearing in an animal model (Long-Evans rat). We report that prenatal cocaine exposure can cause elevated ABR thresholds and latency-intensity curves consistent with a recruitment-type sensorineural hearing loss.     

Plasticity of Peripheral Auditory Frequency Sensitivity in Emei Music Frog

In anurans reproductive behavior is strongly seasonal. During the spring, frogs emerge from hibernation and males vocalize for mating or advertising territories. Female frogs have the ability to evaluate the quality of the males'' resources on the basis of these vocalizations. Although studies revealed that central single torus semicircularis neurons in frogs exhibit season plasticity, the plasticity of peripheral auditory sensitivity in frog is unknown. In this study the seasonally plasticity of peripheral auditory sensitivity was test in the Emei music frog Babina daunchina, by comparing thresholds and latencies of auditory brainstem responses (ABRs) evoked by tone pips and clicks in the reproductive and non-reproductive seasons. The results show that both ABR thresholds and latency differ significantly between the reproductive and non-reproductive seasons. The thresholds of tone pip evoked ABRs in the non-reproductive season increased significantly about 10 dB than those in the reproductive season for frequencies from 1 KHz to 6 KHz. ABR latencies to waveform valley values for tone pips for the same frequencies using appropriate threshold stimulus levels are longer than those in the reproductive season for frequencies from 1.5 to 6 KHz range, although from 0.2 to 1.5 KHz range it is shorter in the non-reproductive season. These results demonstrated that peripheral auditory frequency sensitivity exhibits seasonal plasticity changes which may be adaptive to seasonal reproductive behavior in frogs.     

Effects of long-term heat exposure on the auditory nerve-brainstem evoked responses

1. 1.|The purpose of this study was to determine whether chronic latency changes were induced in the auditory nerve-brainstem potentials (ABR) during long-term heat exposure (acclimation).

2. 2.|Latency prolongations of the ABR were observed during acute (5 days) heat exposure. This was followed by a shortening of latencies and amplitude elevation after long-term (2 months) heat exposure (acclimation).

3. 3.|It was concluded that long-term exposure to heat induces chronic changes in nervous activity.

Adult Plasticity in the Subcortical Auditory Pathway of the Maternal Mouse

Subcortical auditory nuclei were traditionally viewed as non-plastic in adulthood so that acoustic information could be stably conveyed to higher auditory areas. Studies in a variety of species, including humans, now suggest that prolonged acoustic training can drive long-lasting brainstem plasticity. The neurobiological mechanisms for such changes are not well understood in natural behavioral contexts due to a relative dearth of in vivo animal models in which to study this. Here, we demonstrate in a mouse model that a natural life experience with increased demands on the auditory system – motherhood – is associated with improved temporal processing in the subcortical auditory pathway. We measured the auditory brainstem response to test whether mothers and pup-naïve virgin mice differed in temporal responses to both broadband and tone stimuli, including ultrasonic frequencies found in mouse pup vocalizations. Mothers had shorter latencies for early ABR peaks, indicating plasticity in the auditory nerve and the cochlear nucleus. Shorter interpeak latency between waves IV and V also suggest plasticity in the inferior colliculus. Hormone manipulations revealed that these cannot be explained solely by estrogen levels experienced during pregnancy and parturition in mothers. In contrast, we found that pup-care experience, independent of pregnancy and parturition, contributes to shortening auditory brainstem response latencies. These results suggest that acoustic experience in the maternal context imparts plasticity on early auditory processing that lasts beyond pup weaning. In addition to establishing an animal model for exploring adult auditory brainstem plasticity in a neuroethological context, our results have broader implications for models of perceptual, behavioral and neural changes that arise during maternity, where subcortical sensorineural plasticity has not previously been considered.