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Biomedical subjects

C R Goodlett

Publications and source records attributed to C R Goodlett.

50 records · Page 3Linked to original sources
PubMed1983

Attenuation of reversal deficits of mice with septal lesions by shifts in the motivational context.

Response perseveration following septal lesions, demonstrated on tasks that require change of a learned pattern of responding, depends in part on a relatively constant motivational context. The present experiment examined the effects of concurrent changes in the temperature of the water in a water-escape maze and the reversal of a spatial discrimination in mice that had received either septal lesions or control surgery. Control and experimental mice were trained on a spatial discrimination in either 17 or 34 degrees C water. Following acquisition, reversal training was conducted in the maze filled with the same-temperature water used during acquisition or water temperature as well as spatial reinforcement contingencies were reversed. When the water temperature remained constant across acquisition and reversal, the mice with septal lesions showed persistence during reversal training. Changing the water temperature concurrently with the institution of reversal training attenuated the perseverative deficits of mice with lesions, in contrast to the relative lack of effect in control animals. These results are discussed within the framework of the role that the septal region plays in attention.

Animals↗
PubMed1982

Influence of environmental rearing history and postsurgical environmental change on the septal rage syndrome in mice.

Reactivity to handling was examined in Binghamton Heterogeneous (HET) mice given septal lesions or control surgery following 5 weeks of postweaning rearing in enriched or restricted environments. Three housing conditions were employed: continuous enrichment, continuous restriction (both pre- and postsurgically), and a group switched from environmental enrichment to restriction 24 hours after surgery. The restricted mice were more reactive to handling than the enriched mice presurgically (60 days old), and interactions of housing conditions and surgery were found over the seven day postsurgical handling and testing period. The restricted mice given septal lesions greatly increased in reactivity postsurgically, while the intact controls declined in reactivity over the postsurgical week. The enriched septals were only moderately increased over the low presurgical reactivity baseline, and were much less reactive than the restricted septals. Perhaps the most remarkable finding was the dramatic and immediate increase in reactivity in the septals switched from enrichment to restriction, while intact controls showed no effect of the switch. These results emphasize the importance of experience in determining the effects of septal damage, and may be useful in examining other correlates of septal rage.

Analysis of Variance↗
PubMedDate not supplied

Alteration in the pattern of nerve terminal protein immunoreactivity in the perforant pathway in Alzheimer's disease and in rats after entorhinal lesions.

Neurons in layer II of the entorhinal cortex consistently develop neurofibrillary tangles in Alzheimer's disease (AD). Experimental neuroanatomical studies have shown that these neurons give rise to the perforant pathway, a major excitatory projection to the hippocampal formation, which terminates in a discrete pattern in the outer portion of the molecular layer of the dentate gyrus. The distribution of two nerve terminal associated proteins, synaptophysin and NT75, was studied in the molecular layer of the dentate gyrus in AD and control cases to determine whether Alzheimer neuronal pathology is associated with loss of synaptic markers. In parallel studies, the effect of ablation of the entorhinal cortex in rats was evaluated. In AD as compared to controls, a decrease in synaptophysin immunostaining was evident in the terminal zone of the perforant pathway. NT75 nerve terminal immunostaining was too weak to interpret in the human hippocampal formation. Both synaptophysin and NT75 immunoreactivity were found in association with some neuritic plaques. In rats, entorhinal lesions resulted in diminished immunoreactivity for both synaptophysin and NT75 in the perforant pathway terminal zone. These results suggest that nerve terminal protein loss is a concomitant feature of neuronal pathology in AD.

Aged↗
PubMedDate not supplied

Blood alcohol concentration and severity of microencephaly in neonatal rats depend on the pattern of alcohol administration.

A rat model of third trimester fetal alcohol exposure was used to examine how the pattern of administration of a daily alcohol dose influences the pattern of blood alcohol concentrations (BACs) and the severity of brain growth restriction. Four groups of rats were artificially reared from postnatal days 4 to 10. Three of the groups received an equivalent daily dose of alcohol (6.6 g/kg/day) but in different daily patterns. To one group, the dose was administered continuously in a 2.5% (v/v) solution; in two other groups, the dose was condensed into either 7.5% or 15.0% (v/v) solutions. A fourth group (gastrostomy controls) received a formula containing maltose-dextrin, which was isocaloric to the 2.5% alcohol solution. BACs were determined twice daily at times designed to estimate the daily peak and minimum BACs. The rats were killed on postnatal day 10 and total brain weights, cerebellar weights and brainstem weights were measured. In each of the three groups given alcohol, the maximum BAC occurred on the afternoon of postnatal day 6. Thereafter, daily peak BAC declined progressively. The more concentrated the pattern of alcohol administration, the higher was the maximum BAC achieved and the more severe was the interference with brain growth. While the group receiving the alcohol dose in small continuous fractions (2.5%) did not exhibit any significant microencephaly, relative to gastrostomy controls, the groups receiving the dose in more concentrated forms (7.5% and 15.0%) exhibited significant brain growth restriction (reduced 19% and 31%, respectively, relative to controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMedDate not supplied

Brain growth deficits following a single day of alcohol exposure in the neonatal rat.

Alcohol (7.5 g/kg) was administered to neonatal rats in a single day via artificial rearing procedures, being given in four consecutive feedings spaced two hours apart on either postnatal day 4, 5, or 6. These single days of alcohol exposure resulted in high peak blood alcohol concentrations (mean peak BACs of 380, 439 and 460 mg/dl, respectively) and significantly restricted brain weight when measured on postnatal day 10. The cerebellum was affected more than total brain, forebrain or brain stem. Additionally, growth of the cerebellum was more stunted by alcohol exposure on either day 4 or 5 than when the alcohol exposure occurred on day 6. Small but significant delays in body growth occurred 1-2 days after the alcohol exposure for each group. The interference with brain growth following high BACs for a short period of time has important clinical and experimental implications related to binge drinking and the mechanisms underlying alcohol-induced effects on the developing brain.

Animals↗
PubMedDate not supplied

A single day of alcohol exposure during the brain growth spurt induces brain weight restriction and cerebellar Purkinje cell loss.

The period of rapid brain growth that occurs relatively late in development has been shown to be vulnerable to alcohol-induced brain growth deficits and neuron loss in rats using repeated daily exposure to alcohol. This study examined whether a condensed exposure (binge) restricted to a single day during this period would be sufficient to restrict brain growth and produce neuron depletion. Using artificial rearing, alcohol was given to neonatal rats in two consecutive feedings on postnatal day 4, using a total dose of either 6.6 g/kg or 3.3 g/kg. The higher dose produced mean peak blood alcohol concentrations of 362 mg/dl, while the lower dose produced mean peak BACs of 153 mg/dl. The higher dose significantly restricted whole brain, forebrain, cerebellum and brain stem weights on postnatal day 10, with the cerebellum being most severely reduced. Cerebellar Purkinje cells, counted from a 2-microns section from the midsagittal vermis, were significantly reduced in the 6.6 g/kg group. Purkinje cell loss relative to controls was significant in the most lobules (I-V, IX and X), but, notably, was not significant in the later maturing regions (lobules VI and VII). The 3.3 g/kg group had no significant reductions in regional brain weights. Although the overall number of Purkinje cells was nonsignificantly reduced relative to controls, the 3.3 g/kg dose did produce significant loss of Purkinje cells in lobule II. Exposure to high peak BACs, even for a relatively short period during the brain growth spurt, constitutes a substantial risk to the developing brain, and even a moderate exposure may result in loss of more vulnerable neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Prenatal ethanol exposure during the last third of gestation in rat reduces hippocampal NMDA agonist binding site density in 45-day-old offspring.

The effect of ethanol exposure during different periods of prenatal or postnatal development on hippocampal N-methyl-D-aspartate (NMDA) receptor binding was studied in rat. Fetal rat pups were exposed to ethanol for different periods of time during gestation via maternal consumption of a 3.35% ethanol liquid diet. In a separate experiment, neonatal pups were fed 2.51 g ethanol/kg body weight/day from Postnatal Day (PD) 4 to PD 10 via intragastric feeding tube. These two ethanol administration paradigms produced average peak maternal and pup blood ethanol concentrations of 39 mg/dl and 57 mg/dl, respectively. At 45 days of age, offspring from each treatment group were sacrificed for measurements of hippocampal NMDA-sensitive [3H]-glutamate binding site density using in vitro radiohistochemical techniques. As observed previously, prenatal ethanol exposure throughout gestation resulted in NMDA-sensitive [3H]-glutamate binding site reductions in the apical dendritic field regions of dentate gyrus, hippocampal CA1 and subiculum of dorsal hippocampal formation compared to the ad lib or pair-fed control groups. NMDA-sensitive [3H]-glutamate binding was not different than control in rats exposed to ethanol during the first half of gestation only. Prenatal ethanol exposure during the last half or the last third of gestation resulted in NMDA-sensitive [3H]-glutamate binding site reductions comparable to the binding site reductions observed in rats exposed to ethanol throughout gestation. Hippocampal NMDA-sensitive [3H]-glutamate binding site density in postnatal ethanol-exposed rats was not different than the suckling or gastrostomy control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMedDate not supplied

Alcohol reduces the number of pheochromocytoma (PC12) cells in culture.

Pheochromocytoma (PC12) cells were used as an in vitro neuronal cell model to examine detrimental effects of alcohol on cell numbers. Alcohol exposure (100, 200, 400, and 800 mg/dl) reduced PC12 cell numbers in a dose-dependent manner. Cells that were treated with nerve growth factor (NGF) incurred less severe reductions in numbers compared with cells that were never treated with NGF. Because NGF stops proliferation of many of the PC12 cells and differentiates them into neuronal-like cells, these data suggest that differentiated, nonproliferating cells are less vulnerable to alcohol-induced reductions in cell numbers. In a subsequent experiment using only undifferentiated PC12 cells, alcohol reduced cell number of both proliferating and nonproliferating cultures; however, the reductions in proliferating cultures were more severe than in nonproliferating cultures. Two mechanisms may account for alcohol-induced reductions of PC12 cell numbers--inhibition of proliferation and killing of cells. PC12 cell cultures are a useful model system to examine mechanism(s) underlying alcohol's depletion of neuronal-like cells.

Animals↗
PubMedDate not supplied

Developing rat Purkinje cells are more vulnerable to alcohol-induced depletion during differentiation than during neurogenesis.

This study compared the extent of cerebellar Purkinje cell depletion induced by administering alcohol to rats during two temporally distinct periods of Purkinje cell development--neurogenesis and early differentiation. One group received alcohol (5 g/kg/day) during and shortly after Purkinje cell neurogenesis (gestational days 13-18) via oral intubation of pregnant dams. A second group received alcohol (2.5 g/kg/day) during early Purkinje cell differentiation (postnatal days 4-9) via artificial rearing of pups. The two alcohol treatment protocols were designed to match the cyclic daily blood alcohol profiles of the two groups as closely as possible. Pair-fed intubated controls, artificially reared gastrostomy controls, and normally reared ad lib/suckle controls were also evaluated. Mean peak blood alcohol concentrations (BACs) were 266 mg/dl for the intubated pregnant dams and 205 mg/dl for the pups exposed postnatally. Purkinje cell profiles were counted from single, 2-microns-thick midsaggital sections on postnatal day 10. Alcohol exposure during neurogenesis resulted in no significant change in Purkinje cell profile densities. Exposure during differentiation produced significant reductions in Purkinje cell profile densities, predominantly in the early maturing regions of the vermis (lobules I-IV and IX-X). These results indicate that Purkinje cells are more vulnerable to alcohol-induced population depletion during differentiation than during neurogenesis.

Animals↗
PubMedDate not supplied

Long-term deficits in cerebellar growth and rotarod performance of rats following "binge-like" alcohol exposure during the neonatal brain growth spurt.

The cerebellum is vulnerable to growth restriction and neuronal depletion induced by alcohol exposure during the brain growth spurt of neonatal rats. This study examined whether neonatal alcohol exposure permanently restricted brain growth and induced motor performance deficits in adults. Two groups of rats were given 4.5 g/kg of alcohol per day during postnatal days 4 through 9, using artificial-rearing procedures. One group was given the alcohol as a 10.2% (v/v) solution in two of the 12 daily feedings, producing peak BACs of 361 mg/dl. The second group was given the alcohol as a 5.1% (v/v) solution in four of the feedings, producing peak BACs of 187 mg/dl. Controls included an artificially reared group and a normally reared group. All rats were tested on a rotarod at approximately 405 days of age, then perfused 1-2 weeks later. The 10.2% group was significantly impaired in acquiring the task and had significant reductions in whole brain and cerebellar weight, compared to controls. The 5.1% treatment also significantly restricted whole brain and cerebellar growth, and rotarod performance of that group was intermediate between the control groups and the 10.2% group. The cerebellar reductions and deficits in motor performance in adulthood demonstrate permanent structural and functional consequences of binge-like alcohol exposure during the brain growth spurt.

Animals↗
PubMedDate not supplied

Neonatal binge ethanol exposure using intubation: timing and dose effects on place learning.

Neonatal rats were given ethanol using an acute intubation procedure that resulted in daily binge-like exposure with minimal effects on somatic growth. Acquisition of place learning in the Morris water maze was evaluated on postnatal days (PD) 26-31. In Experiment 1, a total of 5.25 g/kg/day of ethanol was administered in two daily intubations on PD 4-6, PD 7-9, or PD 4-9, producing mean peak BACs of 265 mg/dL. Place learning acquisition deficits in a 114-cm-diameter tank were found for the PD 4-9 and PD 7-9 groups, but not the PD 4-6 group. In Experiment 2, either 4.5 or 5.25 g/kg/day of ethanol was administered on PD 7-9 and place learning was tested in a 171-cm-diameter tank. Significant acquisition deficits resulted from the higher dose, and probe trial search patterns for both ethanol groups were significantly less localized than controls. In Experiment 3, no significant effects of either PD 7-9 dose were found on a visible platform task. These findings reveal selective place learning deficits in this intubation model of neonatal binge exposure, and confirm a temporal window of vulnerability to spatial learning deficits during the second neonatal week.

Animals↗
PubMedDate not supplied

Binge neonatal alcohol intubations induce dose-dependent loss of Purkinje cells.

Previous work using artificial rearing methods to administer alcohol to neonatal rats identified postnatal days (PD) 4-6 as a period of enhanced vulnerability to alcohol-induced Purkinje cell loss. To develop an alternative to artificial rearing, alcohol was administered to pups in a binge pattern of exposure using acute intubations, and dose-related effects on blood alcohol concentrations (BACs), somatic growth, and cerebellar Purkinje cell survival were assessed. Pups were intubated with alcohol in milk formula, twice a day, 2 h apart, with total daily doses of 4.5, 5.25, or 6.0 g/kg of alcohol. After intubations on PD 4, the blood alcohol concentration (BAC)-time curves systematically increased with increasing dose. Intubation of these doses on PD 4-6 produced significant, dose-dependent reductions in the total number of cerebellar Purkinje cells on PD 10, counted using the stereological optical fractionator. Somatic growth was significantly affected only by the highest dose. These dose manipulations using intubations confirmed that Purkinje cell death systematically increased as a function of BAC profiles within the PD 4-6 window of vulnerability.

Alcohol Drinking↗
PubMedDate not supplied

Therapeutic motor training ameliorates cerebellar effects of postnatal binge alcohol.

We have used training on complex motor tasks to ameliorate effect of neonatal alcohol exposure. On postnatal days 4-9, alcohol-exposed (AE) rats were given 4.5 g/kg/day of alcohol by artificial rearing; gastrostomy control (GC) rats were given an isocaloric mixture of maltose/dextrin; suckling control (SC) rats were suckled normally. At 6 months of age, animals from the three groups underwent either rehabilitation training on a series of complex motor tasks, motor conditioning on a flat runway, or an inactive home cage condition. Subsequently, animals were either tested on three tests of balance and coordination, or were used for cerebellar morphology. After rehabilitation, but not after motor conditioning, male and female AE rats exhibited significant improvement in independent tests of motor skills. Using unbiased stereological morphological techniques, rehabilitated SC and AE animals were found to exhibit significantly more parallel fiber synapses per Purkinje cell in the paramedian lobule.

Animals↗