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Biomedical subjects

D R Moore

Publications and source records attributed to D R Moore.

At least 91 records · Page 5Linked to original sources
PubMed1989

Relative contributions of protein sulfhydryl loss and lipid peroxidation to allyl alcohol-induced cytotoxicity in isolated rat hepatocytes.

The time course of allyl alcohol-induced toxicity was studied in freshly isolated rat hepatocytes. The sequence of events was as follows: an initial, rapid depletion of glutathione (GSH), a subsequent increase in malondialdehyde (MDA) and decrease in protein sulfhydryl groups (PSH), and the eventual loss of membrane integrity. The sulfhydryl compounds, N-acetylcysteine and dithiothreitol, markedly delayed the depletion of GSH, prevented significant loss of PSH, and protected the cells against viability loss. In contrast, the antioxidants, butylated hydroxytoluene and Trolox C, and the iron-chelating agent, deferoxamine, suppressed allyl alcohol-induced MDA production without affecting the depletion of cellular thiols or the loss of viability. The results suggest that the inactivation of protein thiol groups is critical for allyl alcohol toxicity whereas lipid peroxidation is not essential to the toxic process.

1-Propanol↗
PubMed1989

Auditory brain stem of the ferret: some effects of rearing with a unilateral ear plug on the cochlea, cochlear nucleus, and projections to the inferior colliculus.

To examine the influence of acoustic experience on the development of the mammalian auditory brain stem, darkly pigmented ferrets were reared with a plug inserted in the right outer ear. The plugs were first inserted on postnatal day 23-34 and produced a variable, frequency-dependent attenuation of up to 60 dB. Between 3-15 months after the ear plug was begun, animals were prepared for physiological recording and injection of wheat germ agglutinin-HRP (WGA-HRP) in the left inferior colliculus (IC). The plug was removed and the condition of the right ear was assessed by pure-tone stimulation and recordings from neurons in the left IC. Neural audiograms for each animal showed a residual deficit in most cases. Following 24-60 hr survival, the animals were perfused and the right ear was examined. Brain-stem sections were reacted with tetramethylbenzidine. Outer and/or middle ear pathology was present in over half of the animals. However, the cochleas appeared to be normal and the spiral ganglion cells were normal by several quantitative criteria: number, area, and nucleolar eccentricity. The volume of each division of the cochlear nuclei (CN) and the areas of individual neurons in the anteroventral CN were the same on the right and left sides. The number of CN neurons retrogradely labeled from the left IC injection of WGA-HRP was found to be significantly increased in the left CN, relative to normal animals, when expressed as a ratio of the number labeled in the right CN. We conclude that the residual hearing loss in the previously plugged ears was predominantly or exclusively conductive. Neonatal, unilateral conductive hearing loss in the ferret does not lead to degeneration of the CN on the side of the loss, but it does lead to at least one rearrangement of auditory brain-stem connectivity. We suggest that the extent to which the brain stem is modified by early auditory deprivation is dependent on the type, degree, and symmetry of the hearing loss.

Animal Husbandry↗
PubMed1988

An anomaly in the auditory brain stem projections of hypopigmented ferrets.

The number of cochlear nucleus (CN) neurones projecting to the ipsi- and contralateral inferior colliculus (IC) was studied in darkly pigmented and hypopigmented ferrets by the retrograde transport of wheat germ agglutinin-horseradish peroxidase. The contralateral projection in all divisions of the CN of both albino and 'red eyed' ferrets was normal. However, the ipsilateral projection from the anteroventral CN was significantly smaller in albino than in pigmented ferrets. The volume of each division of the CN was also measured and was found to be the same in albinos as in pigmented animals. The results show that hypopigmented ferrets have at least one anomaly among the connections of the auditory brain stem.

Albinism↗
PubMed1988

Effect of aging on aqueous-phase antioxidants in tissues of male Fischer rats.

The purpose of this study was to determine the influence of aging on concentrations of the important aqueous-phase antioxidants in rat tissues. Ascorbic acid, glutathione and uric acid were measured in tissues and organs of male Fischer 344 rats at 6, 15 and 26 months of age. Blood, liver, lungs, heart, kidneys, brain, testes and lenses were excised rapidly and were extracted with cold metaphosphoric acid. Aging diminished the concentration of ascorbic acid in liver, lung and lens; levels in 26-month-old rats were 40-60% of those in 6-month-old rats. Glutathione content was diminished only in lens, where it decreased almost 50% between 15 and 26 months. Some age-associated increases in antioxidant levels also were seen; testis ascorbic acid and kidney glutathione levels were elevated in the old compared with the younger rats. Uric acid concentrations were much lower than glutathione or ascorbic acid concentrations in every tissue except plasma. Old rats had lower levels of uric acid in liver but higher levels in heart, kidney and testis. These results demonstrate that aqueous-phase antioxidant levels are not uniformly diminished in tissues of old rats.

Aging↗
PubMed1988

Auditory brainstem of the ferret: effects of unilateral cochlear lesions on cochlear nucleus volume and projections to the inferior colliculus.

Unilateral lesions of the right cochlea were made in ferrets aged postnatal day (P)12 to P93. The extent of the lesions was assessed by counting remaining hair cells and ganglion cells in midmodiolar sections through the lesioned cochleas and by comparison with a sample of unlesioned cochleas. The neural effects of the lesions were assessed by measuring the volume of each cochlear nucleus (CN) and by counting the number of neurons in each CN that were retrogradely labeled following injections of WGA-HRP in the left inferior colliculus (IC). Survival times between lesioning and injection of the tracer ranged from 11 to 98 days. CN volume and projections to the IC were also measured in a sample of normal adult ferrets and in normal infants aged P39 to P80. Cochlear lesions resulted in a reduction of the volume of the CN on the lesioned side, relative to the other CN, in animals of all ages and survival times. The extent of the CN volume reduction was negatively correlated with the number of remaining cochlear ganglion cells. However, even where the number of ganglion cells was within the normal range, significant volume reductions occurred. The ventral CN was more severely affected by the lesions than the dorsal CN, but no difference was found between the anteroventral and posteroventral divisions of the nucleus. There was no significant difference in the extent of CN volume reductions between animals of different ages or survival times. Lesions of the right cochlea in younger animals (P14 to P24) resulted, after 90 days survival, in an increase in the number of left CN neurons projecting to the left IC. No significant increase was seen following lesions in older (P90) ferrets or following short (11 or 30 days) survival times in young (P14 to P24) ferrets. The extent of the increase in the ipsilateral CN-IC projection was not related to the number of remaining ganglion cells or to the division of the CN examined. Lesions did not affect the contralateral CN-IC projection. We conclude that cochlear lesions in infant ferrets can alter auditory brainstem morphology and connectivity. The dependence of these alterations on the age of the animal, survival time following lesion, and extent of the lesion varies markedly with the index examined.

Animals↗
PubMed1988

Auditory brainstem of the ferret: sources of projections to the inferior colliculus.

The organization of the auditory brainstem in adult, darkly pigmented ferrets was studied by using the retrograde transport of the lectin wheat germ agglutinin-horseradish peroxidase injected into one inferior colliculus. Retrogradely labelled neurons were found bilaterally in every nucleus of the auditory brainstem. The greatest number of labelled neurons was found in the cochlear nuclei contralateral to the injection site, the ipsilateral medial superior olivary nucleus, both lateral superior olivary nuclei, the ipsilateral ventral nucleus of the lateral lemniscus, both dorsal nuclei of the lateral lemniscus, and the contralateral inferior colliculus. Quantitative assessment of the projections from the cochlear nuclei showed that the number of contralaterally projecting neurons exceeded the number of ipsilaterally projecting neurons by about 50 to one. This ratio remained relatively stable over a wide range of volumes of injected lectin, whereas the absolute number of labelled neurons on each side varied by at least twofold for a constant volume of lectin. These results provide basic data on the ferret auditory system and demonstrate quantitatively some properties of the projections between the cochlear nucleus and the inferior colliculus.

Animals↗
PubMed1988

Developmental plasticity in the visual and auditory representations in the mammalian superior colliculus.

Environmental factors play an important role in certain aspects of the development of sensory systems. But the way in which the maturation of different sensory modalities is coordinated is poorly understood. We have investigated this question neurophysiologically in the mammalian superior colliculus (SC), which contains topographically aligned maps of visual and auditory space. We report here that an essentially normal auditory map, in approximate register with the visual map, is found in the SC of adult ferrets reared with abnormal binaural localization cues. Also, if, early in life, one eye is deviated laterally, there is a compensatory shift in the auditory map, but early eye rotation totally disorders the auditory representation. These results imply that development of the auditory map is affected by visual activity or by information about eye position and that there is definite, but limited, capacity for the auditory map to reorganize so that it remains aligned with the visual map.

Acoustic Stimulation↗
PubMed1988

Acetaminophen hepatotoxicity in aging rats.

Severity of liver damage 24 hr after i.p. administration of acetaminophen in doses of 0.4 and 0.8 g/kg was evaluated in male Fischer 344 rats at 4, 14 and 25 months of age. Both doses of acetaminophen produced significant elevations of serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities in 4-month-old rats. Enzyme release was somewhat diminished in old age. Hepatic glutathione (GSH) and microsomal cytochrome P-450 concentrations were decreased in rats that received 0.8 g/kg of acetaminophen. The decreases occurred in young-adult and middle-aged rats, but not in old rats. The results demonstrated that old age does not enhance the hepatotoxic effects of acetaminophen in male Fischer 344 rats.

Acetaminophen↗
PubMed1987

Effect of age and sex on allyl alcohol hepatotoxicity in rats: role of liver alcohol and aldehyde dehydrogenase activities.

Allyl alcohol-induced hepatotoxicity was more severe in old male rats than in young-adult male rats, as measured by release of hepatic enzymes from injured cells and loss of hepatic microsomal cytochrome P-450. The extent of toxicity in female rats was greater than in males and was unaffected by aging. The purpose of this study was to examine possible causes for these differences. The activity of alcohol dehydrogenase (ADH) with allyl alcohol as substrate was measured in liver cytosolic fractions of rats at ages representing young adulthood, middle age and old age. ADH activities were 1.7 +/- 0.1, 2.3 +/- 0.1 and 2.6 +/- 0.1 mumol/min/g of liver in male rats aged 4, 14 and 25 months, respectively. ADH activities in young-adult and old female rats were 3.8 +/- 0.1 and 3.7 +/- 0.1 mumol/min/g of liver. There was a good correlation (r = 0.99, P less than .001) between liver ADH activity and allyl alcohol-induced hepatotoxicity, measured as the release of sorbitol dehydrogenase into the bloodstream. Cytosolic free NAD+/NADH ratios in male rats were not significantly different among the three age groups; the ratios were lowest in young-adult female rats. Low Km aldehyde dehydrogenase activities in liver mitochondrial and cytosolic fractions were similar among the three age groups of male rats, and the activities in female rats were not substantially different. The results indicated that increased ADH activity is the principal cause of the age-associated enhancement of allyl alcohol hepatotoxicity in male rats.

1-Propanol↗
PubMed1986

Cochlear nucleus lesions in the adult gerbil: effects on neurone responses in the contralateral inferior colliculus.

Unilateral cochlea ablation in neonatal gerbils has previously been shown to result in transneuronal degeneration of the ventral cochlear nucleus (CN) and enhanced responses of neurones in the contralateral inferior colliculus (IC) to ipsilateral stimulation of the non-ablated ear. Neither effect occurs in adult-ablated animals. To determine whether the lack of physiological change in the adult is due to the persistence of the ventral CN we lesioned the left CN of adult gerbils and recorded neurone responses in the right IC to stimulation of the right ear. Neurone thresholds, latency and intensity/response functions were unaffected by the lesion. The proportion of recording loci in the IC at which excitatory responses were obtained was also unaffected. A transient increase was observed in the maximum unit discharge level. The findings suggest that CN lesions in adults do not produce either the range or degree of neuronal changes resulting from neonatal cochlea ablation and the subsequent transneuronal degeneration of the CN. Thus, the effects of cochlea ablation are age-dependent.

Animals↗
PubMed1986

Central and peripheral contributions to coding of acoustic space by neurons in inferior colliculus of cat.

Recordings of response to free-field stimuli at best frequency were made from single units in the central nucleus of the inferior colliculus of anesthetized cats. Stimulus position was varied in azimuth, and the responses of units were compared with variation in the intensity and arrival time of the sound at each ear, derived from cochlear microphonic (CM) recordings. CM recordings were made at each frequency and at every point in space for which single-unit data were collected. Interaural time difference (delay) increased monotonically, but not linearly, as the stimulus was moved away from the midline. However, a given delay did not represent a single azimuth across frequency. Low-frequency interaural intensity differences (IIDs) were monotonic across azimuth and peaked at, or near, the poles. Higher-frequency IIDs were nonmonotonic and peaked relatively close to the midline, decreasing toward the poles. Units that showed little variation in discharge across azimuth formed 28% of the sample and were classified as omnidirectional. For other units, the spike-count intensity function and the variation of the CM with azimuth were combined to form a derived monaural azimuth function. For 29% of those units showing azimuthal sensitivity, the derived monaural azimuth function matched the actual azimuth function. This suggested that these units received input from only one ear. The largest group of azimuthally sensitive units (47%) was formed from those units inferred to be IID sensitive. At higher frequencies these units displayed a peaked azimuth function paralleling the nonmonotonic relation of IID to azimuth. The proportion of inferred IID-sensitive units was close to that found in dichotic studies.

Acoustic Stimulation↗
PubMed1985

Projections from the cochlear nucleus to the inferior colliculus in normal and neonatally cochlea-ablated gerbils.

The distribution of the projection from one cochlear nucleus (CN) within each inferior colliculus (IC) was studied in adult, normal gerbils and adult gerbils subjected to unilateral ablation of the contralateral cochlea at 2 days of age. The projection was studied by using the Fink-Heimer technique for impregnating degenerating axons and their terminal processes with silver. Following an extensive, unilateral lesion of the CN, degeneration was seen in both ICs of all animals. In normal animals, degeneration was both more widespread and heavier in the contralateral than in the ipsilateral central nucleus of IC (ICC). Degeneration was most widespread in the rostral and lateral parts of both ICCs and in the ventral part of the contralateral ICC. Degeneration was observed in 26% of the area examined in ipsilateral ICC and in 73% of the area examined in contralateral ICC. In cochlea-ablated animals there was a much greater similarity in the area of degeneration in the ICC ipsilateral (57%) and contralateral (67%) to the CN lesion. The same regional distributions of degeneration were observed as in the normal animals except that the distribution of degeneration in the ipsilateral ICC more closely resembled the normal contralateral than the normal ipsilateral profile. We conclude that the normal distribution of projections from the CN within the ipsilateral ICC is substantially modified by neonatal ablation of the contralateral cochlea.

Animals↗
PubMed1985

Postnatal development of the mammalian central auditory system and the neural consequences of auditory deprivation.

The auditory system of many mammalian species is immature at the time of birth. Peripheral elements, particularly the middle ear and cochlea, account for much of the physiological immaturity observed in central auditory structures. However, there is now considerable evidence that the central pathway undergoes developmental changes that, at least partially, occur in parallel with peripheral development. Auditory nerve fibres and their terminals have been shown to be of smaller diameter and less extensively arborized in neonatal than in adult cats. These factors almost certainly contribute to many of the sluggish physiological properties of neurones in the kitten auditory nerve and cochlear nucleus. At higher levels of the cat auditory system (inferior colliculus, auditory cortex) mechanisms subserving binaural interaction also undergo a period of postnatal development. Recent studies of sound deprivation produced by either deafferentation or a conductive hearing loss have demonstrated that alteration of cochlear output during the immediate postnatal period may change the normal development of the central auditory system.

Animals↗
PubMed1984

Properties of spatial receptive fields in the central nucleus of the cat inferior colliculus. I. Responses to tones of low intensity.

Single neurones in the central nucleus of the inferior colliculus (ICC) of barbiturate-anesthetized cats were examined using free-field, pure-tone stimuli of low intensity at the neurones' best frequency. Receptive field size was inversely correlated with best frequency. Almost all neurones were maximally excited by stimulus positions in the hemifield contralateral to the recording electrode, irrespective of their best frequency. Simultaneous cochlear microphonic recording revealed that the neurones' best excitatory area was also the spatial region associated with maximum amplification by the contralateral outer ear. This amplification resulted in extremely low (less than -20 dB SPL in some neurones) best frequency thresholds. Response patterns were found not to vary markedly with speaker position. The results suggest that most ICC neurones are more sensitive to stimulation of the contralateral ear than to stimulation of the ipsilateral ear.

Animals↗
PubMed1984

Properties of spatial receptive fields in the central nucleus of the cat inferior colliculus. II. Stimulus intensity effects.

Single units in the central nucleus of the inferior colliculus (ICC) of barbiturate-anaesthetized cats were studied using pure-tone, best-frequency stimulation presented in the free field. At low stimulus intensities almost all neurones responded most strongly to stimuli positioned along the acoustical axis of the pinna contralateral to the recording electrode and there was little or no response to stimuli positioned in the ipsilateral hemifield. Four major classes of spatial response were distinguished when tones of moderate to high intensity were used. The simplest response (24% of the sample) to increasing intensity consisted of a monotonic increase in discharge level at all effective speaker positions and an expansion of the area of space from which a stimulus influenced the response (receptive field). A second class (21%) of units had a nonmonotonic increase in discharge level and an expanding receptive field with increasing intensity. Neither of these classes showed evidence of influence from the ipsilateral ear. The third class (26%) developed, at higher intensities, a second excitatory response region in the ipsilateral hemifield. The fourth class (20%) had receptive fields with fixed medial borders, irrespective of intensity. The third and fourth classes of units were thought to be binaurally influenced and to be sensitive to interaural phase and intensity differences, respectively.

Animals↗
PubMed1983

Some acoustic properties of neurones in the ferret inferior colliculus.

Single neurones in the central nucleus of the ferret inferior colliculus (ICC) were studied using extracellular recording. Responses to pure tone stimuli were analyzed to assess the frequency organization of the nucleus, the sensitivity and tuning properties of neurones and the effects of binaural sound presentation. Excitatory tuning curves had the characteristic shape found for neurones in the auditory systems of other species. Many ferret neurones were inhibited by stimulus frequencies on either side of the range producing excitatory responses. Sharpness of excitatory tuning was found to be comparable with that reported for the cat. Neurones having best frequencies in the range 4-15 kHz showed the greatest sensitivity. All electrode penetrations revealed a dorsal-to-ventral progression of neurones of increasing best frequency. Some neurones were classified according to the predominant type of input from each ear. Over 80% of these units were binaurally influenced. Nearly all cells received an excitatory input from the contralateral ear and about one-third of those units were excited by ipsilateral stimulation. The remainder showed either a simple inhibitory ipsilateral input or ipsilateral inhibition that was manifested as a suppression of the excitatory, contralateral response. These experiments demonstrate that the ferret may be a satisfactory alternative to other carnivores for studies of the auditory system.

Animals↗