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C R Goodlett

Publications and source records attributed to C R Goodlett.

At least 37 records · Page 2Linked to original sources
PubMed1990

Regional differences in the timing of dendritic outgrowth of Purkinje cells in the vermal cerebellum demonstrated by MAP2 immunocytochemistry.

Detailed, within-subjects Golgi analyses of regional differences in cerebellar Purkinje cell dendritic development are impractical due to the capriciousness of that technique. Immunocytochemical labeling of microtubule-associated protein 2 (MAP2) was used to reveal the dendritic development of Purkinje cells, and indicated marked differences in the timing of initial outgrowth of Purkinje cell dendrites for different lobules in the developing rat cerebellar vermis. In particular, an early maturing region of Purkinje cell dendritic outgrowth (lobules I, II, IX and X and along the primary fissure), and a late maturing region (distal lobule VI, lobule VII and dorsal lobule VIII) were documented.

Aging↗
PubMed1990

New approaches to research on the long-term consequences of prenatal exposure to alcohol.

As the summary presentation of a symposium on prenatal alcohol-induced brain damage and long-term postnatal consequences, this paper proposes the establishment of two main research priorities--to begin to correlate long-term behavioral effects with alterations in underlying neural substrates, and to explore the mechanisms of neuroteratogenicity. To reach these goals, three objectives are described. First, animal and human research must become more interrelated. Second, experimental observations should be integrated into formal models that incorporate both neural structure and function. Third, researchers should choose well-defined dependent measures that are derived from models of brain function based on modern concepts of cognitive neuroscience. Examples of neuropsychological tests that may serve as the bases for structure/function relationships are presented. Incorporating these objectives into future research will facilitate understanding of the fundamental issues concerning prenatal alcohol exposure and will begin to provide the bases for rational intervention or treatment.

Alcohol Drinking↗
PubMed1990

Cell population depletion associated with fetal alcohol brain damage: mechanisms of BAC-dependent cell loss.

Neuronal death is one of the most serious consequences of alcohol exposure during development. Studies described in this paper used a neonatal rat model to address factors affecting neuronal death following alcohol exposure during the period of rapid brain growth, and relate them to possible mechanisms of damage. The profile of blood alcohol concentrations (BACs) is an important variable influencing both brain growth deficits and neuronal death--a smaller daily dose of alcohol can be more damaging than a larger daily dose, if it is consumed in a binge-like pattern that produces relatively higher BACs. Alcohol exposure for a single day also can be damaging, producing both brain growth deficits and neuron loss, if high BACs are obtained. Various brain regions and different neuronal populations within a given brain area exhibit different degrees of vulnerability. Some neuronal loss clearly is a function of cell death due to direct effects of alcohol, while other deficits may be due to either primary or secondary effects of the alcohol insult. In the cerebellum, a maturational or metabolic factor also appears to be involved with alcohol-induced neuronal death. Immunocytochemical studies using a monoclonal antibody against microtubule-associated protein 2 (MAP2) indicated that cerebellar lobules containing Purkinje cells that are in the process of extending dendrites are ones that are more vulnerable to alcohol than lobules containing Purkinje cells that mature later. Alcohol exposure during brain development may be producing neuron attrition in multiple ways, including disruption of membrane integrity, inhibition of protein synthesis or other alterations such as lipid solubility, or by disruption of cytoskeletal elements.

Animals↗
PubMed1990

Teratogenic effects of alcohol on brain development.

There is convincing evidence that alcohol is teratogenic both in humans and animals and that its most devastating effects are on the developing brain. However, much information is still needed to determine the circumstances that increase the risk and severity of fetal alcohol-induced brain damage and to identify the mechanisms underlying such damage. Animal research has been used to address these issues because, for the most part, they are unapproachable experimentally in humans. In the past, the rather restricted focus of research into the teratology of alcohol has led to several theoretical biases. Recent findings conflict with these biases. Alcohol-induced damage to the developing brain encompasses a longer developmental time-frame, affects more cell populations, occurs at lower levels of exposure, produces greater numbers of permanent effects, and is modulated by more factors than was initially suggested by earlier teratological studies.

Abnormalities, Drug-Induced↗
PubMed1989

Alz-50 immunoreactivity in the neonatal rat: changes in development and co-distribution with MAP-2 immunoreactivity.

Alz-50 is a monoclonal antibody that recognizes pathological alterations in Alzheimer's disease. It has recently been noted also to mark some subplate neurons in human infants under the age of 2 years. We now report that Alz-50 recognizes many neurons in the normal neonatal rat in a pattern that changes with development. Immunoreactivity decreases substantially in intensity as the rat matures. This immunoreactivity co-distributes with microtubule-associated protein-2 (MAP-2) immunoreactivity in terms of topography, cellular localization and changes over the developmental time-course. This observation raises the possibility of exploring cytologic triggers that may lead to re-expression of Alz-50 immunoreactivity in aging and in pathological conditions.

Alzheimer Disease↗
PubMed1989

Long-term deficits in water maze spatial conditional alternation performance following retrohippocampal lesions in rats.

The effects of large bilateral retrohippocampal lesions on long-term performance of conditional spatial alternation, incorporating a strong working memory component, were examined using a T-maze task motivated by swim-escape. The lesions, which included entorhinal cortex, subiculum, pre- and parasubiculum and invaded the molecular layer of the dentate gyrus, completely eliminated the previously acquired conditional alternation learning, and performance failed to recover with 40 days of testing. These findings support the contention that retrohippocampal structures are an important and necessary component of the neural circuitry mediating working memory.

Animals↗
PubMed1989

Differential neuronal loss following early postnatal alcohol exposure.

Neonatal rats were exposed to 6.6 g/kg of alcohol each day between postnatal days 4 and 10 while artificial-rearing procedures were used, in a manner which produced high peak and low trough blood alcohol concentrations each day. Gastrostomy controls were reared artificially with maltose/dextrin isocalorically substituted for alcohol in the milk formula, and suckle controls were reared normally by dams. The pups were sacrificed on day 10 and tissue sections (2 microns thick) were obtained in the sagittal plane through the cerebellum and in the horizontal plane through the hippocampal formation. Overall area measures were obtained for the hippocampus proper, area dentata, and cerebellum, along with areas of the cell layers of these regions. In the hippocampal formation, cell counts were made of the pyramidal cells of the hippocampus proper, the multiple cell types of the hilus, and the granule cells of the area dentata. In the cerebellum, cell counts of Purkinje cells, granule cells of the granular layer, granule cells of the external granular layer, and mitotic cells of the external granular layer were obtained from lobules I, V, VII, VIII, and IX. Alcohol selectively reduced areas and neuronal numbers in the cerebellum but had no significant effects on neuronal numbers in the hippocampal formation. Purkinje cells exhibited the greatest percent reductions, and cerebellar granule cells were significantly reduced in the granular layer but not in the external granular layer. All lobules showed these effects, but lobule I was significantly more affected than the other four lobules that were analyzed. The results demonstrate the differential vulnerability of selected neuronal populations to the developmental toxicity of alcohol exposure during the brain growth spurt.

Analysis of Variance↗
PubMed1989

Genetic influences on brain growth restriction induced by development exposure to alcohol.

Genetic factors have been implicated as contributing to the considerable variation in the severity of alcohol-related birth defects in offspring of women who drink heavily during pregnancy. Two animal models of alcohol-related developmental effects incorporated different behavior genetic approaches to examine genetic influences on brain and body growth following alcohol exposure during development. The first, extensively developed in Sprague-Dawley rats, examined the effects of three doses of alcohol administered to two inbred rat strains (MR and M520) via artificial-rearing procedures during the early postnatal brain growth spurt. In both strains, alcohol produced a dose-dependent restriction of brain weight (but not body weight) on postnatal day 10, compared to artificially reared controls. The MR strain was more susceptible to cerebellar growth restriction than the M520 strain, an effect not attributable to strain differences in blood alcohol concentrations. In the second model, pregnant female Long-sleep and Short-sleep mice, selectively bred for differences in initial sensitivity to the hypnotic effects of acute alcohol administration, were intubated with ethanol from gestational days 7-18. Controls included either sucrose or maltose/dextrin intubation controls and non-intubated controls. The LS offspring showed growth deficits and brain weight reductions in adulthood, while the SS offspring were resistant to these detrimental effects of the prenatal alcohol exposure. Thus, differences in either maternal or fetal genotype may contribute to individual differences in the severity of the effects of alcohol exposure during development.

Animals↗
PubMed1989

Manipulating peak blood alcohol concentrations in neonatal rats: review of an animal model for alcohol-related developmental effects.

Fetal alcohol syndrome (FAS) is now well documented, but factors that affect the severity of the accompanying central nervous system damage are still not well understood. In a series of experiments, artificially reared neonatal rats were exposed to alcohol during postnatal days 4-10 (during the brain growth spurt of the rat) to evaluate the consequences of various patterns of alcohol consumption in contributing to the severity of alcohol-related brain damage. In the first experiment, groups of rat pups were given different doses of alcohol (6.6 to 9.8 g/kg) in a milk formula in eight 15-min feedings over each 24 hr. Measures of brain weight on day 10 indicated an inverse relationship between dose and brain weight. Re-evaluating the results with respect to blood alcohol concentration (BAC) revealed an even stronger correlation between BAC and microencephaly. A series of experiments followed in which various doses of alcohol were condensed into fewer and fewer hours each day. Condensing the dose produced higher BACs for a given dose and produced more severe microencephaly, greater neuronal loss, behavioral hyperactivity and impaired spatial navigation. Some of these effects were permanent with females more affected than males on some measures. These data suggest that patterns of alcohol consumption that produce high BACs, such as binge drinking, may be especially harmful to the brain of the developing fetus.

Animals↗
PubMed1988

Impaired spatial navigation in adult female but not adult male rats exposed to alcohol during the brain growth spurt.

Two groups of male and female rats were given the same dose of alcohol using an artificial rearing procedure on postnatal days 4-10. One group received the alcohol in a condensed manner each day which caused cyclic blood alcohol concentrations (BACs) with high peaks. A second group received the alcohol in a uniform manner over each day which resulted in moderate, stable BACs. Two control groups consisted of male and female rats artificially reared but not exposed to alcohol and rats reared normally by dams. All rats were raised to 90 days of age and then tested for spatial navigation ability in the Morris water maze, which involved locating a hidden underwater platform using distal extramaze cues. Neither the alcohol treatments nor the artificial rearing had any effects on performance of adult male rats relative to suckle controls in this task. In contrast, the condensed alcohol exposure but not the uniform alcohol exposure resulted in detrimental performance in the Morris water maze by adult female rats. When the ability to locate and escape onto a visible platform was examined, there were no differences between the female groups given condensed alcohol exposure or artificially reared on milk solution alone. Thus, exposure to high BACs during the brain growth spurt has a lasting and selective detrimental effect on spatial navigation learning in adult female but not adult male rats.

Animals↗
PubMed1988

Constraints on water maze spatial learning in rats: implications for behavioral studies of brain damage and recovery of function.

In an effort to develop spatial learning tasks not requiring food or water deprivation for use in studies of recovery of function after brain damage, T-maze spatial alternation learning was examined in intact rats using water maze swim-escape procedures. Consistent with previous studies, rewarded spatial alternation involving food or water deprivation was readily learned by intact rats. However, none of the groups of rats trained in the swim-escape tasks learned to alternate goal arm choices in the water maze at reliable rates. This was true regardless of whether non-correction or correction procedures were used, and regardless of intertrial delay intervals. Although average alternation rates over sessions did increase from chance levels, the majority of the rats did not reach criterion levels, even with as many as 38 consecutive days of testing. In contrast, a conditional spatial alternation task in the water maze, using a win-shift procedure, was readily learned. Surprisingly, a win-stay version of this conditional spatial task was not learned over 21 days of testing. These unexpected constraints on spatial learning and memory processes in rats cannot be attributed simply to failure of spatial information processing, nor to strict limitations on working memory in swim-escape tasks, since excellent spatial navigation abilities have been documented, and mastery of at least some working-memory tasks have now been demonstrated in swim-escape tasks.

Animals↗
PubMed1988

Time course and reversibility of ethanol's suppressive effects on axon sprouting in the dentate gyrus of the adult rat.

Ethanol was administered chronically to adult rats in a liquid diet for 14 days preceding and for 5, 7, 8, 9, or 10 days following the unilateral destruction of the entorhinal cortex. Control groups received a diet of lab chow and water and were sacrificed at comparable survival times. An additional experimental group was given ethanol until 9 days after the lesion, then switched to lab chow and water and sacrificed 1 day later. Coronal sections through the dorsal hippocampal formation were stained and analyzed histochemically for the localization of acetylcholinesterase (AChE). Quantitative measurements of the histochemical patterns in the molecular layer of the dentate gyrus were obtained. Ethanol exposure inhibited the withdrawal of the acetylcholinesterase-stained septohippocampal fibers and limited the typical lesion-induced expansion of the pale-staining commissural/associational zone in the molecular layer of the denervated dentate gyrus. However, abstinence from ethanol for just 24 h released the inhibitory effect on the acetylcholinesterase-staining fibers, resulting in a significant expansion of the commissural/associational zone.

Animals↗
PubMed1987

Sprouting responsiveness in the dentate gyrus is reduced by ethanol administered following but not preceding an entorhinal lesion.

We examined the effect of ethanol on lesion-induced sprouting in the molecular layer of the dentate gyrus. Adult rats were fed a liquid diet containing either ethanol or sucrose for 14 days before and 9 days following unilateral entorhinal cortex lesions. One group was provided the ethanol diet ad libitum during both the pre- and postlesion period. Three other groups were pair-fed to the latter group; one consumed ethanol prelesion, one postlesion, and one did not receive ethanol. Sections through the rostral hippocampus were stained for histochemical localization of acetylcholinesterase. Following the entorhinal lesion the pale-staining commissural/associational zone ipsilateral to the lesion typically expands and exhibits decreased acetylcholinesterase staining. When ethanol was administered after the lesion, expansion of the commissural/associational zone was significantly diminished compared with the two groups that received the control diet after the lesion. Ethanol administered for 2 weeks before the lesion had no measurable effect on commissural/associational zone expansion. These findings imply that, at least for short-term exposure, ethanol reduces the sprouting responsiveness of systems in the dentate gyrus only during the postlesion period when sprouting normally occurs.

Acetylcholinesterase↗
PubMed1987

Effects of pre- and early postnatal protein malnutrition on carcass composition and lipoprotein lipase activity in male rats.

Little is known about the effects of pre- and early postnatal protein malnutrition on energy storage (e.g., carcass lipid) and expenditure (e.g., brown adipose tissue [BAT] thermogenesis) and their reversibility by nutritional rehabilitation. Therefore, the purpose of these experiments was to examine the permanence of prenatal and early postnatal protein malnutrition on energy balance in rats. Five weeks before mating and through gestation adult female rats were fed either a 25 or 8% casein diet (designated 25 or 8). Diet reversals were performed at birth and/or at weaning (designated B or W) and the pups were cross-fostered at birth. Thus, the groups were: 25-25B (controls), 8-25W (gestational and lactational protein malnutrition, 8-25B (gestational protein malnutrition), and 25-8B-25W (lactational protein malnutrition). Animals were weighed and sacrificed 200-250 days postpartum for carcass composition. Retroperitoneal white adipose tissue (RWAT) and interscapular BAT (IBAT) wet weights and lipoprotein lipase (LPL) activity were also measured in the 25-25B and 8-25W groups. Nutritional rehabilitation at birth (8-25B) resulted in normal body weights as adults. Lactational protein malnutrition (25-8B-25W) resulted in intermediate body weights to the controls (25-25W), which had the greatest weights, and the 8-25W group, which had the lowest weights. The 8-25W and 25-8B-25W rats also had significantly decreased carcass wet weight and total body water, fat and fat-free dry mass relative to the 25-25B and 8-25B groups, the latter two of which did not differ in their carcass composition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1987

Differential effects of clonidine, B-HT 933 and B-HT 920 in immature rat pups.

The effects of the alpha-adrenergic agonist clonidine were compared with two experimental hypotensive drugs, B-HT 920 and B-HT 933, in 10-day-old rat pups. Clonidine induced the expected dose-dependent (0.1-1.0 mg/kg) motor activation and wall-climbing syndrome typical at this age. B-HT 933, thought to be a more selective alpha 2-agonist than clonidine, elicited locomotor activity and wall-climbing only at the highest dose used (50 mg/kg). The high dose of B-HT 933 necessary to begin to mimic the effects of clonidine, a finding consistent with some studies using B-HT 933 in adults, suggests that the wall-climbing syndrome is mediated by receptors which have a low affinity for B-HT 933. In striking contrast, B-HT 920, a presynaptic dopamine agonist in mature rats, produced a very different behavioral profile. B-HT 920 induced long periods of sniffing accompanied by locomotion at low doses (peak at 0.12 mg/kg) and ataxic locomotion and poorly coordinated wall-climbing at high doses (30-50 mg/kg). Experiment 2 demonstrated that the active sniffing evoked by low doses of B-HT 920 was dose-dependently blocked by haloperidol (0.035-1.0 mg/kg). These findings of behavioral effects in 10-day-old rats suggest that B-HT 920 stimulates dopaminergic receptors in immature rats, presumably located on postsynaptic neurons. We propose that B-HT 920 and B-HT 933 also may be differentiated in terms of the time of onset of functional development of dopaminergic and noradrenergic autoreceptors, respectively.

Animals↗
PubMed1986

Spatial cue utilization in chronically malnourished rats: task-specific learning deficits.

Rats whose mothers were maintained on either a 25% casein diet or an 8% casein diet and who were provided the same diet after weaning were tested on delayed spatial alternation or on one of a series of spatial localization problems using the Morris maze (Morris, 1981). Malnourished rats demonstrated perseverative deficits in the form of strings of consecutive errors on the delayed spatial alternation. Performance in the Morris maze indicated spatial localization ability and spatial memory processes were not impaired by chronic malnutrition in rats. The data suggest that complex processing of spatial information that includes flexible use of place cues over short intervals is impaired by malnutrition, while spatial localization per se and spatial mapping are not affected.

Animals↗
PubMed1985

Altered development of responsiveness to clonidine in severely malnourished rats.

To examine the effects of malnutrition on the ontogeny of alpha 2 noradrenergic receptor function, we compared the effects of clonidine during early development in severely malnourished and well-nourished rat pups. Independent groups of pups from dams given either 6% or 25% casein diets received one of five doses of clonidine at 5, 10, 15, 20 or 25 days of age and dose-response relationships for motor activity were determined. In the 25% pups the clonidine-induced locomotor activity was greatest at 5 and 10 days, intermediate at 15 days and not elevated at 20 and 25 days. The malnourished pups exhibited a significant delay in the transition from hyperactivity to hypoactivity, being activated by clonidine until at least 25 days. Wall-climbing measures indicated similar developmental trends as overall activity. These results are discussed in terms of the proposed mechanisms mediating the developmental change in the effects of alpha 2 receptor stimulation.

Aging↗