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Biomedical subjects

L D Fechter

Publications and source records attributed to L D Fechter.

At least 55 records · Page 3Linked to original sources

Prenatal carbon monoxide exposure differentially affects postnatal weight and monoamine concentration of rat brain regions.

Regional weight, protein concentration, and monoamine concentration were determined in the pons/medulla, neocortex, hippocampus, and cerebellum of 21- and 42-day-old offspring of rats exposed to either air or 75, 150, or 300 ppm carbon monoxide (CO) throughout pregnancy. Norepinephrine and serotonin concentrations decreased linearly with increasing CO exposure concentrations in the pons/medulla of CO-exposed offspring at 21 days of age, but not by 42 days of age. Norepinephrine concentration increased linearly with increasing CO exposure concentrations in neocortex and tended to increase in hippocampus of CO-exposed offspring at 42 days of age, but not at 21 days of age. Regional weights and protein concentrations of the neocortex, hippocampus, or pons/medulla were not affected by CO exposure at either age. Cerebellar weights of CO-exposed offspring, however, decreased linearly with increasing CO exposure concentrations at both 21 and 42 days after birth. No significant effect of CO exposure on cerebellar monoamine concentrations was observed. The results suggest that prenatal CO exposure disrupts the development of noradrenergic and serotonergic neuronal systems, and the development of the cerebellum.

Animals↗

Alteration in the postnatal ontogeny of cerebellar norepinephrine content following chronic prenatal carbon monoxide.

The postnatal ontogeny of norepinephrine content in the cortex and cerebellum was determined in rats exposed prenatally to a chronic low level of carbon monoxide (150 parts per million). In the cerebellum, norepinephrine concentration and total norepinephrine content among carbon monoxide-exposed rats were consistently elevated over that of control rats from the second through the sixth postnatal weeks. In the cortex, norepinephrine concentration and total norepinephrine content among carbon monoxide-exposed rats did not differ from that of control rats over the same period. These results identify the cerebellum as a region whose postnatal development is altered by prenatal exposure to low levels of carbon monoxide-induced hypoxia.

Animals↗

Prenatal exposure to carbon monoxide: learning and memory deficits.

Exposing pregnant rats to carbon monoxide (150 parts per million) produced only minor reductions in the birth weights of the pups and gave no evidence of overt teratogenesis. However, behavioral evaluation of learning and memory processes in a two-way avoidance task suggested a functional deficit in the central nervous system of the exposed offspring. Multiple dependent measures and specific control groups confirmed that this deficit was independent of nonassociative or motivational alterations.

Animals↗

Diethyldithiocarbamate depresses the acoustic startle response in rats.

The relationship between norepinephrine (NE) content in cortex and spinal cord and acoustic startle amplitude was investigated in two experiments. Administration of diethyldithiocarbamate (DDC) depressed startle amplitude at the same time and dose that it most severely depleted NE content. These results support the conclusion that NE facilitates the normal elaboration of the acoustic startle reflex and also support evidence that NE activity in the spinal cord may be of particular importance in the maintenance of normal startle amplitude.

Acoustic Stimulation↗

Discrimination of auditory from nonauditory toxicity by reflex modulation audiometry: effects of triethyltin.

The evaluation of toxicity in sensory systems presents particular problems because of the need to distinguish specific sensory loss from other toxic effects. It has recently been shown that modulation of reflex behavior by low-intensity test stimuli can be used to provide a rapid assessment of sensory acuity and of ototoxic hearing loss. In this report the ability of the method to distinguish the known neuromuscular consequences of triethyltin (TET) from hearing loss is demonstrated. Rats treated with TET bromide (30 mg/liter) in their drinking water for 3 weeks showed a profound decrease in acoustic startle reflex amplitudes which was apparent prior to overt neuromuscular weakness and subsequent hindlimb paralysis. Following cessation of treatment, startle levels recovered to preexposure values. Despite these large changes in startle reflex amplitudes, TET treatment did not alter the ability of pure tone stimuli to modulate reflex behavior. These results indicate that TET as administered in these studies disrupted neuromuscular function but did not affect hearing.

Analysis of Variance↗

Reflex inhibition procedures for animal audiometry: a technique for assessing ototoxicity.

A procedure for making rapid audiometric assessments of animal subjects, based on the ability of weak stimuli to modify the strength of reflexes elicited by subsequently presented strong stimuli, is described. Pure-tone detection thresholds for rats and guinea pigs determined by this procedure are quite comparable to those determined by operant techniques, and are similarly sensitive to ototoxic insult. The procedure is also applicable to the assessment of suprathreshold sensory function, and offers advantages over commonly used procedures for assessing ototoxicity.

Animals↗

Prenatal carbon monoxide exposure alters behavioral development.

The potential for mild prenatal carbon monoxide (CO) exposure by means of maternal cigarette smoking or industrial and ambient air sources is extremely high, but the biological consequences and, in particular, the neurobehavioral effects are undetermined. We have exposed pregnant rats to 150 ppm in air and examined the behavioral development of the infant rats using tests of righting reflexes, negative geotaxis and homing. The offspring of CO exposed rats weigh less at birth and show reduced growth rates prior to weaning. Cross fostering does not ameliorate the retarded growth curves of experimental subjects. Behavioral testing revealed poorer than normal performance on the negative geotaxis and homing tests among the CO exposed rats. No difference in steady state brain catecholamine levels was seen between groups. The results complement an earlier report showing reductions in locomotor activity following mild prenatal CO exposure and indicate that such exposure has significant functional consequences for the developing rat.

Animals↗

Prenatal carbon monoxide and adult evoked potentials in rats.

Hooded rats prenatally exposed to mild carbon monoxide hypoxia were studied as adults. Flash evoked potentials were recorded from the visual cortex of unanesthetized exposed and control rats at four different flash intensities. The amplitude of bothe the P1-N1 and N1-P2 components on the flash evoked potential were significantly greater in CO-exposed female rats than in control females. The experiments thus demonstrate long term alterations in CNS function from exposure to relatively mild levels of CO.

Animals↗

Toxicity of mild prenatal carbon monoxide exposure.

Rats prenatally exposed to a low concentration of carbon monoxide which results in carboxyhemoglobin levels equivalent to those maintained by human cigarette smokers, show reduced birth weight and decreased weight gain. Neuro-behavioral and biochemical testing of the offspring reveals lower behavioral activity levels through the preweaning period, altered central catecholamine activity, and reduction in total brain protein at birth.

Animals↗

Disruption of neostriatal development in rats following perinatal exposure to mild, but chronic carbon monoxide.

The vulnerability of the developing neostriatum to mild, but chronic hypoxia was evaluated in weanling rats exposed only in utero or from conception through postnatal day 10 to 0, 75, 150, and 300 ppm carbon monoxide (CO). The exposure conditions produced maternal carboxyhemoglobin (HbCO) levels of about 11, 19, and 27 percent. HbCO levels of 5 percent are maintained by human cigarette smokers while comparable levels in non-smokers average less than 1%. Significant elevations in DNA and the neurotransmitter, dopamine (DA), were observed in the striatum of 21-day-old rats following the combined pre- and neonatal CO exposure. These neurochemical changes were observed 11 days after CO exposure was terminated and, therefore, cannot be interpreted as acute responses to reduced oxygen. These data indicate that the immature neostriatum is altered by even mild hypoxic insults presented during the time of neuronal proliferation and synaptogenesis.

3,4-Dihydroxyphenylacetic Acid↗

Trimethyltin ototoxicity in albino rats.

The toxicity of alkyltin compounds is of exceptional interest due to the dissimilar toxic effects of some very closely related structural analogues among this class of compounds. Since several features of the toxicity of trimethyltin appeared to be consistent with a mechanism involving accumulation of the toxicant on melanin pigments, the ototoxicity induced by TMT exposure was examined in albino rats. Hearing thresholds for tones sampling the mid- and high-frequency range of the rat's audibility function were assessed by reflex inhibition audiometry. TMT produced a frequency dependent loss of auditory sensitivity that was most severe in the high frequency range. The TMT-induced impairment of auditory function was similar to that previously observed in pigmented Long-Evans rats. These results extend the observation of TMT-induced hearing loss to a non-pigmented rodent strain and suggest that the accumulation of TMT on cochlear melanin is not critical to the production of hearing impairment by TMT.

Animals↗

Brain regional manganese levels and monoamine metabolism in manganese-treated neonatal rats.

The brain distribution of manganese (Mn) and the regional steady state levels of monoamines and their metabolites in normal and Mn-treated neonatal rats have been investigated. Neonatal rats were intubated daily with distilled water, 25 or 50 micrograms manganous chloride/g/day for 14 or 21 days. Manganese levels in brain regions and liver were analyzed by flameless atomic absorption spectroscopy. Norepinephrine, dopamine, serotonin and their metabolites in the striatum, hypothalamus, and nucleus accumbens were analyzed by HPLC. The levels of Mn in Mn-treated animals were increased at 14 and 21 days of age although brain levels at 21 days were lower than those at 14 days. Monoamine and metabolite levels were not altered by Mn treatment in any region at either age. Thus, increases in brain Mn levels do not necessarily result in alterations in steady state neurotransmitter and metabolite levels. These results suggest that the neurotoxic effects of these doses of Mn administered to neonatal animals are not expressed as alterations in steady state levels of monoamines and metabolites. The developing nervous system may be able to compensate for neurochemical changes caused by Mn exposure.

Aging↗

Trimethyltin disrupts auditory function and cochlear morphology in pigmented rats.

Trimethyltin (TMT) produces auditory deficits, presumably of cochlear origin, in rats. The present study identified pathological changes in the cochlea following treatment with TMT and correlated them with auditory threshold changes. Thresholds were determined by reflex-modulation audiometry, before and after treatment with TMT or with saline vehicle. Animals were then perfused and their cochleas embedded for examination as block-surface preparations or radial sections. In the first week following treatment, all TMT-treated rats showed threshold shifts of 40 to 60 dB at 40 kHz, and smaller threshold shifts (10-25 dB) at 2.5 and 10 kHz. At 3 weeks they showed threshold shifts similar to those identified one week following treatment, but with some recovery at 10 kHz. At 10 weeks, one animal showed complete recovery and three showed recovery of function at 10 but not at 40 kHz. TMT-treated animals showed losses of outer hair cells (OHC) in the basal turn of the cochlea as early as 48 hours following exposure. Comparable OHC pathology was seen at 9 days, along with some losses of inner hair cells. More extensive pathology occurred at longer survival times including the loss of type 1 spiral ganglion cells. The loss of auditory sensitivity at high frequencies was closely related to the loss of outer hair cells in the basal turn of the cochlea.

Animals↗