Acoustic trauma causes reversible stiffness changes in auditory sensory cells

A common cause of hearing impairment is exposure to loud noise. Recent research has demonstrated that the auditory mechanosensory cells are essential for normal hearing sensitivity and frequency selectivity. However, little is known about the effect of noise exposure on the mechanical properties of the auditory sensory cells. Here we report a significant reduction in the stiffness and cell length of the outer hair cells after impulse noise exposure, suggesting that mechanical changes at the cellular level are involved in noise-induced hearing loss. There is a recovery of the cellular stiffness and cell length over a two-week period, indicating an activation of cellular repair mechanisms for restoring the auditory function following noise trauma. The reduced stiffness observed at the cellular level is likely to be the cause for the downward shift of the characteristic frequency seen following acoustic trauma. The deterioration and the recovery of the mechanical properties of outer hair cells may form important underlying factors in all kinds of noise-induced hearing loss.     

Functional NMDA receptors are transiently active and support the survival of Purkinje cells in culture

Conflicting evidence exists concerning the activity of NMDA receptors (NMDARs) in cerebellar Purkinje cells and their possible functions. To investigate the activity of NMDARS, we used whole-cell recording on immunocytochemically identified Purkinje cells in primary culture. In addition, we used mice with a disrupted NMDAR1 gene that lack functional NMDARs (NR1-/-) to assess the physiological role of NMDARs. In cultures from normal mice, NMDA-medicated currents were detected in all identified Purkinje cells at 4 d in vitro (div). After 14 d, however, NMDA responses were reduced in amplitude, whereas the responses to kainate and glutamate increased steadily in amplitude. In addition, the NMDA-induced current displayed a pronounced desensitization at these later stages; peak current declined to zero during steady application of NMDA. At 7 div, the number of surviving Purkinje cells was less in cultures treated with NMDA antagonists, and their survival was dose-dependent. Purkinje cell survival was correspondingly poorer in cultures from the NR1-/- mice than in wild-type controls, suggesting that NMDAR activity enhances the survival of Purkinje cells in vitro. The addition of moderate doses of NMDA promoted the survival of wild-type Purkinje cells in the presence of tetrodotoxin. Feeder layers of cerebellar granule cells derived from wild-type or NR1-/- mice promoted survival of Purkinje cells to a similar degree, suggesting that the NMDAR in Purkinje cells, but not in other cells, is directly involved in Purkinje cell viability. The results demonstrate that NMDARs transiently produce membrane current in Purkinje cells and may serve as one of the epigenetic factors that support the survival of Purkinje cells in vitro.     

Putative liver progenitor cells: conditions for long-term survival in culture

BACKGROUND AND OBJECTIVES: We operated on three patients with leiomyosarcoma of the inferior vena cava. METHODS: Complete excision was possible in all three patients. RESULTS: One patient developed widespread metastasis at 23 months, one patient is alive with no evidence of disease at 70 months, and one patient is alive at 15 months. The third patient had subcutaneous and pulmonary metastases at the time of presentation, which are radiologically nondetectable at present following postoperative chemotherapy. CONCLUSIONS: The clinicopathologic features, prognostic factors, and treatment of 130 cases found in a comprehensive literature search and our three cases are reported.     

Electrophysiological evidence of developmental changes in the duration of auditory sensory memory

In behavioral studies, children's memory for tonal frequency has been found to persist for less time than adults' (T. A. Keller & N. Cowan, 1994). The present study was done to evaluate the argument that this effect is due to changes in auditory sensory memory and not to attentional mechanisms. This question was investigated using mismatch negativity (MMN), an auditory event-related potential considered to be insensitive to attention. Participants were 6-7-, 8-10-, and 11-12-year-old children and adults. They were presented with trains of stimuli, beginning with either a standard (1000 Hz) or a deviant (1200 Hz) tone with trains separated by either 1 s or 8 s. All 4 groups exhibited MMNs after delays of 1 s, but only the adults and oldest children exhibited MMNs after 8 s, indicating that there are maturational changes in the duration of auditory sensory memory.     

Hair cell recovery in the vestibular sensory epithelia of mature guinea pigs

The progression of recovery of the vestibular sensory epithelia of guinea pigs after gentamicin-induced hair cell injury was assessed quantitatively and qualitatively. Evaluations were made of the number of cells bearing hair bundles by using scanning electron microscopy (SEM) and of identifiable hair cells in thin sections. Both assessment procedures showed that an initial loss of hair cells in utricular maculae is followed by significant recovery in the number of hair cells present. SEM also showed recovery in saccules comparable to that in utricles. During the recovery, progressive maturation of hair bundles, which exhibited features similar to those seen during normal ontogenetic development of hair cells, could be identified. The pattern and extent of hair cell loss and subsequent reappearance revealed by SEM corresponded with that derived from analysis of thin sections. This suggests that repair of nonlethally damaged hair cells is unlikely but, rather, that new hair cells are produced. An apparent decrease in supporting cell numbers was observed coincident with the increase in hair cell numbers. This complements previous morphological observations, which have suggested new hair cells arise from direct, nonmitotic transdifferentiation of supporting cells. The quantitative analyses indicate that more than half of the hair cells that are lost are replaced, but the recovery process does not result in complete restoration of the epithelium. Eight months after the end of drug treatment, the number of hair cells present was still significantly less than normal, and several other abnormalities persisted. There was also no evidence of any hair cell recovery in the organ of Corti. Thus, there appear to be limitations on the capacity for spontaneous replacement of lost hair cells in the mammalian inner ear.     

Isolation and long-term survival of adult human sensory neurons in vitro

OBJECTIVE: To determine whether adult human dorsal root ganglion neurons can be isolated and maintained in long-term tissue culture, where they would extend processes. METHODS: Dorsal root ganglia were removed from adult human organ donors within 2 hours of clamping the aorta. They were then treated with enzymes for one hour, triturated to dissociate the neurons and their satellite cells, and the individual neurons were then plated in tissue culture dishes in medium containing serum. RESULTS: Isolated adult human dorsal root ganglion neurons survive in vitro for more than 2 1/2 months, in the absence of exogenously supplied neurotrophins. where they remain electrically excitable and extend processes, CONCLUSIONS: Isolated adult human dorsal root ganglion neurons survive in culture for more than 2 1/2 months, extend processes, and remain electrically excitable, without exogenous neurotrophins. These results suggest that, adult human sensory neurons do not require exogenous neurotrophins for survival and process outgrowth, or that sufficient factors were provided by the small number of satellite cells in the cultures. In addition, the neurons survive well in spite of an initial period of up to 14 hours of hypoxia, between the time the aorta was clamped and when the plated neurons were placed in an incubator with the appropriate O2/CO2 environment.     

Regulation of opioid receptors in rat sensory neurons in culture

To determine whether opioid receptors in sensory neurons are regulated by chronic exposure to opioids, we assessed the binding of various opioid ligands to membranes derived from isolated rat dorsal root ganglia neurons grown in culture. Equilibrium binding of [3H]diprenorphine onto membranes from cells grown for 13-15 days revealed a saturable binding site with a Kd value of 0.3 +/- 0.2 nM and an approximate Bmax value of 1300 +/- 200 fmol/mg of protein. [3H]Diprenorphine binding increased 3-fold from 1-15 days in culture. The mu receptors represent approximately 70 +/- 11% of the [3H]diprenorphine binding sites, as indicated by saturation binding of [3H]DAMGO. The kappa and delta receptors represent approximately 10 +/- 3% and approximately 5 +/- 2% of the [3H]diprenorphine binding sites, respectively. Preexposure of neurons to 10 microM naloxone for 48 hr up-regulated the receptors by 40%, whereas incubation with 100 nM to 10 microM DAMGO for 48 hr resulted in a significant decrease in the Bmax value of opioid receptors, with a maximum reduction of 70%. The identification of a high level of opioid receptors expressed in isolated sensory neurons and their modulation by opioids demonstrates that cultured sensory neurons are an excellent model with which to study opioid receptor regulation.     

Extent of recovery of function after early sensory deprivation in the rat.

Compared the performances of 400 90- and 150-day-old light-reared and dark-reared Long-Evans rats on rigorous tests of depth and form discriminative abilities in 2 experiments. Significant differences due to rearing and age were found. Exposure to a normal light environment for 60 days was found to partially alter the effects of an early 90-day period of visual deprivation in the case of depth discrimination but to have little impact in the case of form discrimination. It is theorized that the initial deficits in the performance of the dark-reared rats and the extent of recovery of function after exposure to a normal environment are related to the kind of perceptual ability being measured and to the sensitivity of the test. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Normal time course of auditory recognition in schizophrenia, despite impaired precision of the auditory sensory ("echoic") memory code.

Prior studies have demonstrated impaired precision of processing within the auditory sensory memory (ASM) system in schizophrenia. This study used auditory backward masking to evaluate the degree to which such deficits resulted from impaired overall precision versus premature decay of information within the short-term auditory store. ASM performance was evaluated in 14 schizophrenic participants and 16 controls. Schizophrenic participants were severely impaired in their ability to match tones following delay. However, when no-mask performance was equated across participants, schizophrenic participants were no more susceptible to the effects of backward maskers than were controls. Thus, despite impaired precision of ASM performance, schizophrenic participants showed no deficits in the time course over which short-term representations could be used within the ASM system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mismatch negativity and auditory sensory memory evaluation: a new faster paradigm

A new faster paradigm to measure the duration of auditory sensory memory, as indexed by mismatch negativity (MMN) suppression to stimuli presented at increasing inter-stimulus intervals (ISI), is proposed. Trains of three stimuli were delivered at very short ISI (300 ms). The inter-train interval varied according to the memory probe interval (MPI) tested. Trains started randomly with a deviant or standard stimulus (50% each), with their event-related brain potentials subtracted to obtain the MMN. The new paradigm provided MMNs identical to the conventional one at MPIs of 0.4 and 4.0 s in young subjects, and revealed MMN suppression when the MPI was increased to 5.0 s in older subjects. The new paradigm estimates auditory sensory memory duration in one-third the time of conventional MMN.     

Role of activation and sensory stimuli in recovery from lateral hypothalamic damage in the cat.

Analyzed the early stages of recovery from lateral hypothalamic lesions in 30 adult cats. In addition to aphagia and adipsia, neurological examination revealed deficits suggestive of deficient endogenous arousal, including somnolence, catalepsy, akinesia, and sensory neglect. Manipulations (tail pinch and injection of amphetamine) that counteracted these deficits also restored feeding. During recovery from aphagia, feeding gradually became activated by sensory stimuli (sight, feel, and smell) associated with food. These data suggest that activation is an important component in the control of normal feeding. (3? p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impact of sensory acuity on auditory working memory span in young and older adults.

The impact of sensory acuity, processing speed, and working memory capacity on auditory working memory span (L-span) performance at 5 presentation levels was examined in 80 young adults (18–30 years of age) and 26 older adults (60–82 years of age). Lowering the presentation level of the L-span task had a greater detrimental effect on the older adults than on the younger ones. Furthermore, the relationship between sensory acuity and L-span performance varied as a function of age and presentation level. These results suggest that declining acuity plays an important explanatory role in age-related declines in cognitive abilities. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Activation and recovery of the PGE2-mediated sensitization of the capsaicin response in rat sensory neurons

Pro-inflammatory prostaglandins are known to enhance the sensitivity of sensory neurons to various modalities of stimulation, including the excitatory chemical agent, capsaicin. In this report, we examined the capacity of prostaglandin E2 (PGE2) to enhance the capsaicin response recorded from sensory neurons isolated from embryonic rats and grown in culture. Previous work demonstrated that the cyclic adenosine 3',5'-monophosphate pathway mediates initiation of the PGE2-induced sensitization, however, little is known about the pathways regulating the recovery from sensitization. Therefore, we examined the neuronal transduction cascades that control the duration of sensitization. Treatment with PGE2 enhanced the capsaicin-evoked current by two- to threefold, however, this sensitization was transient even in the continued presence of prostaglandin. The duration of sensitization produced by PGE2 was related inversely to the extracellular Ca2+ concentration with the shortest recovery times observed in cells exposed to 2 mM Ca2+-Ringer. Inclusion of the Ca2+ chelator, bis-(o-aminophenoxy)-N, N,N',N'-tetraacetic acid, in the recording pipette greatly lengthened the period of sensitization. Pretreatment with either the nitric oxide synthase inhibitor, nitro-L-arginine methyl ester (L-NAME), or the inhibitor of the cyclic guanosine 3', 5'-monophosphate (GMP)-dependent protein kinase, KT-5823, before the application of PGE2 increased the duration of sensitization even in the presence of 2 mM Ca2+. In contrast, after attaining maximal sensitization in 2 mM Ca2+-Ringer containing L-NAME, the addition of either nitric oxide donors (3-morpholinosydnonimine or s-nitroso-n-acetylpenicillamine) or 8-Br-cyclic GMP led to a rapid decrease in the level of sensitization. In the absence of sensitization, nitric oxide-cyclic GMP modulating agents had no effect on the capsaicin-evoked current. Therefore, these results suggest that capsaicin-induced elevations in intracellular Ca2+ levels lead to an enhanced production of cyclic GMP, via the nitric oxide pathway, that ultimately activates cyclic GMP-dependent protein kinase. This protein kinase inactivates or terminates the sensitization produced by PGE2 by an as yet unidentified mechanism.     

Restoration of sensory gating of auditory evoked response by nicotine in fimbria-fornix lesioned rats

Recordings of auditory evoked potentials in the CA3 region of the hippocampus reveal a decrement in the N40 wave after the presentation of the second of closely paired auditory stimuli (interstimulus interval of 500 ms), a phenomenon known as sensory gating. Previous experiments have suggested the involvement of nicotinic cholinergic systems in auditory sensory processing. The present study examined the effects of lesioning the fimbria-fornix on auditory sensory processing in the hippocampus. Fimbria-fornix lesions resulted in a failure to decrement the N40 wave in the auditory evoked response to the second tone. When nicotine was administered to rats with fimbria-fornix lesions the drug was able to reinstate the normal suppression of the second auditory evoked response. These data support the involvement of nicotinic cholinergic afferents in auditory sensory modulation in the hippocampus.     

Protection of both auditory hair cells and auditory neurons from cisplatin induced damage

Knowledge about body composition is important in metabolic and nutritional studies. In this cross-sectional study the body composition of 403 healthy white Dutch children and adolescents was evaluated by using dual-energy X-ray absorptiometry (DXA). Possible determinants of body composition were analyzed. In 85 subjects the results of bioelectrical impedance analysis (BIA) were compared with DXA. Fat mass, lean tissue mass, and bone mineral content were greater in older boys and girls. Percentage body fat was greater in older girls but not in boys and it was higher in girls than in boys at all ages. From the age of 14 y boys had higher lean tissue mass and bone mineral content than girls. Tanner stage had a significant relation with body composition in both sexes. Percentage body fat was lower in boys in stage 4 than in stage 3 and was higher in consecutive Tanner stages in girls. After adjustment for age, Tanner stage was significantly positively related to lean tissue mass and bone mineral content in boys and girls and to percentage body fat and fat mass in girls. The profession of the parents and the education of the father had a significant negative correlation with percentage body fat and fat mass in girls (P < 0.01). Physical activity was related to lean tissue mass (P = 0.001) but not to fat mass in boys after adjustment for age. A high correlation and a small difference was found between lean body mass by BIA and lean tissue mass by DXA. Body composition in healthy Dutch children and adolescents is related to age, sex, Tanner stage, socioeconomic status, and physical activity.     

Met receptor signaling is required for sensory nerve development and HGF promotes axonal growth and survival of sensory neurons

The development of the nervous system is a dynamic process during which factors act in an instructive fashion to direct the differentiation and survival of neurons, and to induce axonal outgrowth, guidance to, and terminal branching within the target tissue. Here we report that mice expressing signaling mutants of the hepatocyte growth factor (HGF) receptor, the Met tyrosine kinase, show a striking reduction of sensory nerves innervating the skin of the limbs and thorax, implicating the HGF/Met system in sensory neuron development. Using in vitro assays, we find that HGF cooperates with nerve growth factor (NGF) to enhance axonal outgrowth from cultured dorsal root ganglion (DRG) neurons. HGF also enhances the neurotrophic activities of NGF in vitro, and Met receptor signaling is required for the survival of a proportion of DRG neurons in vivo. This synergism is specific for NGF but not for the related neurotrophins BDNF and NT3. By using a mild signaling mutant of Met, we have demonstrated previously that Met requires signaling via the adapter molecule Grb2 to induce proliferation of myoblasts. In contrast, the actions of HGF on sensory neurons are mediated by Met effectors distinct from Grb2. Our findings demonstrate a requirement for Met signaling in neurons during development.     

Endogenous neurotrophin-3 supports the survival of a subpopulation of sensory neurons in neonatal rat

Neurotrophin-3 promotes the differentiation and supports the survival of neuroblasts derived from the neural crest in early development. Neurotrophin-3 also plays an important role in the differentiation and survival of a subpopulation of large sensory neurons after their axons arrive at their targets. Proprioception and mechanoception are lost after gene deletion of neurotrophin-3 or its high-affinity receptor, TrkC. However, the function of neurotrophin-3 during late development and in mature animals is not clear. We have used an antiserum, specific for neurotrophin-3, to neutralize endogenous neurotrophin-3 in postnatal rats to determine its role in late sensory neuron development. Administration of the antiserum for a period of two weeks, but not one week, resulted in a 20% reduction in the number of primary sensory neurons in the dorsal root ganglia and a 19% reduction in the number of myelinated axons in the saphenous nerve. The size distribution histogram also indicated that a subpopulation of large neurons was lost by the neurotrophin-3 antiserum treatment. This neuronal loss was accompanied by reduced cell soma sizes and weights of the ganglia. Immunoreactivities for calbindin and calretinin were reduced in the trigeminal and dorsal root ganglia and nerve fibres surrounding whisker hair follicles. The number of Merkel cells in touch domes labelled with quinacrine and the number of parvalbumin-immunoreactive neurons in the dorsal root ganglia were significantly reduced by the antibody treatment. In contrast, the number of muscle spindles in the gastrocnemius muscle is not reduced by the neurotrophin-3 antiserum. Together, these results indicate that a subpopulation of primary sensory neurons in the neonatal rat requires neurotrophin-3 for their survival and expression of calcium binding proteins. In addition, Merkel cells in touch domes also require neurotrophin-3 for their survival. Thus, endogenous neurotrophin-3 in neonatal rats is critical for the survival and function of a subpopulation of primary sensory neurons and Merkel cells.