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Biomedical subjects

R M Napper

Publications and source records attributed to R M Napper.

13 recordsLinked to original sources
PubMed1998

Therapeutic effects of complex motor training on motor performance deficits induced by neonatal binge-like alcohol exposure in rats . I. Behavioral results.

The effects of complex motor task learning on subsequent motor performance of adult rats exposed to alcohol on postnatal days 4 through 9 were studied. Male and female Long-Evans rats were assigned to one of three treatments: (1) alcohol exposure (AE) via artificial rearing to 4.5.g kg-1 day-1 of ethanol in a binge-like manner (two consecutive feedings), (2) gastrostomy control (GC) fed isocaloric milk formula via artificial rearing, and (3) suckling control (SC), where pups remained with lactating dams. After completion of the treatments, the pups were fostered back to lactating dams, and after weaning they were raised in standard cages (two-three animals per cage) until they were 6 months old. Rats from each of the postnatal treatments then spent 20 days in one of three conditions: (1) inactive condition (IC), (2) motor control condition (MC) (running on a flat oval track), or (3) rehabilitation condition (RC) (learning to traverse a set of 10 elevated obstacles). After that all the animals were tested on three tasks, sensitive to balance and coordination deficits (parallel bars, rope climbing and traversing a rotating rod). On parallel bars, both male and female rats demonstrated the same pattern of outcomes: AE-IC rats made significantly more mistakes (slips and falls) than IC rats from both control groups. After 20 days of training in the RC condition, there were no differences between AE and both SC and GC animals in their ability to perform on the parallel bars test. On rope climbing, female animals showed a similar pattern of abilities: AE-IC rats were the worst group; exercising did not significantly improve the AE rats' ability to climb, whereas the RC groups (SC, GC and AE) all performed near asymptote and there were no significant differences among three neonatal treatment groups. There was a substantial effect of the male rats' heavier body weight on climbing ability, and this may have prevented the deficits in AE rats behavior from being detected. Nevertheless, male animals from all three postnatal treatments (SC, GC and AE) were significantly better on this task after RC. Female and male rats from all three postnatal groups demonstrated significantly better performance on the rotarod task after 20 days of 'rehabilitation'. These results suggest that complex motor skill learning improves some of the motor performance deficits produced by postnatal exposure to alcohol and can potentially serve as a model for rehabilitative intervention.

Aging↗
PubMed1998

Selective synaptic plasticity within the cerebellar cortex following complex motor skill learning.

Complex motor skill learning, but not mere motor activity, leads to an increase in synapse number within the cerebellar cortex. The present experiment used quantitative electron microscopy to determine which synapse types were altered in number. Adult female rats were allocated to either an acrobatic condition (AC), a voluntary exercise condition (VX), or an inactive condition (IC). AC animals were trained to traverse an elevated obstacle course requiring substantial motor coordination to complete. VX animals were housed with unlimited access to running wheels and IC animals received no motor training but were handled briefly each day. Results showed the AC animals to have significantly more parallel fiber to Purkinje cell synapses than both the VX and IC animals. No other synapse type was significantly altered. Thus, the learning-dependent increase in synapse number observed within the cerebellar cortex is accomplished primarily through the addition of parallel fiber synapses.

Analysis of Variance↗
PubMed1997

Therapeutic motor training increases parallel fiber synapse number per Purkinje neuron in cerebellar cortex of rats given postnatal binge alcohol exposure: preliminary report.

Because therapeutic approaches to fetal alcohol effects in humans have been rare, this study explored the rehabilitative effect of complex motor training on an animal model of binge drinking in the third trimester of human pregnancy. Neonatal alcohol exposure induces significant and permanent reductions in Purkinje and granule cell number accompanied by impaired motor behavior in rats. The purpose of this study was to determine: (1) whether the motor skill impairment caused by exposure to alcohol in the early postnatal period could be ameliorated by the learning of a set of complex motor tasks that had been demonstrated to cause synaptogenesis in the cerebellar cortex; and (2) the extent to which cerebellar neurons in alcohol-exposed (AE) rats exhibit synaptic plasticity. The AE group was given 4.5 g/kg/day of ethanol from postnatal days 4 to 9 via an artificial rearing procedure producing a mean peak blood alcohol level of 257 mg/dl. Control groups consisted of a gastrostomy control (GC) group, that received an isocaloric mixture of maltose/dextrin instead of ethanol, and a suckle control (SC) group, that was reared normally by dams. At approximately 6 months of age, animals from the three groups were assigned either to a rehabilitation condition (RC; that received 10 days of training on the motor tasks) or to an inactive condition (IC; where rats stayed in isolation in their cages). Although SC rats were significantly faster to complete the course in the first 5 days of training, there were no differences in ability to perform among animals from all three groups-SC, GC, and AE--at the end of the training period. Unbiased stereological techniques were used to obtain estimates of the number of parallel fiber synapses/Purkinje cell within the cerebellar paramedian lobule. Results showed that the RC rats from the SC and AE groups had significantly more synapses/Purkinje cell than corresponding IC animals. These data demonstrate that rehabilitative intervention (complex motor training) can improve motor performance impaired by postnatal alcohol exposure and that surviving Purkinje neurons retain the capacity for synaptic plasticity.

Alcoholic Intoxication↗
PubMed1996

Structural plasticity of identified glomeruli in the antennal lobes of the adult worker honey bee.

Adult worker honey bees alter their behaviour with age but retain a strong reliance on sensory information from the antennae. The antennae house a diverse array of receptors, including mechanoreceptors, hygroreceptors, olfactory receptors, and contact chemoreceptors, which relay information to the brain. Antennal sensory neurons that project to the antennal lobes of the brain converge onto second-order interneurones to form discrete spheres of neuropil, called glomeruli. The spatial organisation of glomeruli in the antennal lobes of the honey bee is constant, but the central distribution of information from receptors tuned to different sensory modalities is unknown. Here we show that the glomerular neuropil of the antennal lobes undergoes constant modification during the lifetime of the adult worker bee. Changes in morphology are site specific and highly predictable. The total volume of the glomerular neuropil of the antennal lobe increased significantly during the first 4 days of adult life. Each of the five readily identifiable glomeruli examined in this study exhibited a unique pattern of growth. The growth of two of the five glomeruli changed dramatically with the shift to foraging duties. Furthermore, significant differences were identified between the antennal lobes of bees performing nectar- and pollen-foraging tasks. The highly compartmentalized nature of the antennal lobes, the ease with which specific glomeruli can be identified, and the predictability of changes to the antennal lobe neuropil make this an ideal system for examining the mechanisms and behavioural consequences of structural plasticity in primary sensory centres of the brain.

Aging↗
PubMed1996

Purkinje cell deficits in nonhuman primates following weekly exposure to ethanol during gestation.

The most serious features of fetal alcohol syndrome (FAS) are mental retardation and other behavioral problems resulting from alcohol-induced damage to the developing central nervous system (CNS). The mechanism by which alcohol induces its neuroteratogenic effects is unknown. One hypothesis is that gestational alcohol exposure results in a reduction in neuronal number. This study demonstrates that gestational exposure to ethanol in a non-human primate species induces permanent dose-related deficits in the number of cerebellar Purkinje cells. Ethanol was administered via nasogastric tube once per week to 15 gravid pigtailed macaques (Macaca nemistrina) in one of the following doses: 0.0 (intubated controls), 1.2, 1.8, 2.5, 3.3, and 4.1 g/kg/dose. Offspring were reared with parental surrogates and were sacrificed at 6 months of age; 8-microns-thick, parasagittal sections were cut through the paraffin-embedded cerebellar vermis. Purkinje cells were quantified, the length of the Purkinje cell line was determined stereologically, and Purkinje cell linear frequency was calculated. The number of Purkinje cells and their linear frequencies were significantly reduced in the alcohol-treated subjects, and the deficits were dose-dependent. The groups receiving 2.5 g/kg/dose and above were most severely affected and had an average deficit in Purkinje cell number of 11.8%, relative to controls. Alcohol had no effect on the length of the Purkinje cell line. The findings suggest that alcohol-induced reduction in neuronal number may be an important factor underlying the CNS dysfunction in FAS.

Animals↗
PubMed1996

Long-term effect of postnatal alcohol exposure on the number of cells in the neocortex of the rat: a stereological study.

Behavioral and morphological studies suggest that exposure to alcohol during development may cause damage in the neocortex. In this study, rat pups were exposed to alcohol during the brain growth spurt and examined at adulthood to ascertain the long-term effect of alcohol exposure on the neocortex. Four-day-old rat pups were surgically implanted with an intragastric cannula while under ether anesthesia and artificially reared from postnatal day (PN) 4 through PN11. Two of the consecutive 12 daily feeds contained either alcohol (4.5 g/kg; alcohol-exposed) or an isocaloric maltose/dextrin solution (gastrostomy control) from PN4 through PN9. On PN115, animals were perfused intracardially and the brains removed. Unbiased stereological methods were used to determine the neocortical volume, the total number of neurons and glial cells in the entire neocortex and in layer V, and the mean cell volume of neurons or mean nuclear volume of glial cells in layer V. No effect of alcohol was seen in the neuronal population on either cell number or mean cell volume, nor was there any difference in the total number or mean nuclear volume of glial cells in layer V. These findings suggest that neither the entire neocortex nor layer V alone are vulnerable to permanent alcohol-induced cell death.

Animals↗
PubMed1995

Permanent neuronal cell loss in the cerebellum of rats exposed to continuous low blood alcohol levels during the brain growth spurt: a stereological investigation.

This study demonstrates that exposure to an alcohol regimen that resulted in low, uniform blood alcohol concentrations during a period of rapid brain growth can lead to a permanent deficit in the number of Purkinje cells and granule cells in the floccular-parafloccular region of the cerebellum. Sprague-Dawley rat pups were artificially reared and were administered alcohol over postnatal days 4 through 9, a period of brain development similar to that of the human third trimester. Two groups received a daily alcohol dose of 4.5 g/kg, administered either as a 10.2% solution in two of the 12 daily feedings (10.2% group) or as a 5.1% solution in four of the 12 feedings (5.1% group). A third group received a daily dose of 6.6 g/kg administered as a 2.5% solution in every feeding (2.5% group). The condensed patterns of alcohol administration resulted in high peak blood alcohol concentrations with near total clearance while the higher daily dose (6.6 g/kg), administered continuously, resulted in low but continuous blood alcohol concentrations. Pups were allowed to grow to adulthood and killed on postnatal day 115. The total number of Purkinje cells and granule cells in the floccular-parafloccular region of the cerebellum was estimated using unbiased stereological methods. Exposure to alcohol resulted in significant deficits in the number of both Purkinje cells and granule cells at 115 days of age in all three treatment groups. Most importantly a significant deficit of Purkinje cells and granule cells was found following continuous exposure to low blood alcohol concentrations, i.e., in the 2.5% group. The total number of Purkinje cells in the 2.5% group was 2.33 +/- 0.31 x 10(4) compared with 3.18 +/- 0.30 x 10(4) in the artificially reared controls. The total number of granule cells in the 2.5% group and the controls was 1.24 +/- 0.10 x 10(7) and 1.64 +/- 0.19 x 10(7), respectively. These results support the hypothesis that exposure to a continuous, low blood alcohol concentration can result in the death of developing neurons and lead to permanent neuronal deficits. The degree of neuronal loss does not correlate with the magnitude of the peaks of blood alcohol concentration.

Analysis of Variance↗
PubMed1995

Permanent neuronal cell loss in the inferior olive of adult rats exposed to alcohol during the brain growth spurt: a stereological investigation.

The purpose of this study was to examine whether exposure of rat pups to alcohol postnatally over a period of brain development similar to that of the human 3rd trimester results in a permanent loss of cells in the inferior olivary nucleus. It was hypothesized that a deficit of neurons in the inferior olive, the sole source of climbing fibers, may contribute to the cerebellar dysfunction observed following exposure to alcohol during development. Sprague-Dawley rat pups were artificially reared and administered alcohol over postnatal days 4-9. One artificially reared group received a daily alcohol dose of 4.5 g/kg, administered as a 10.2% solution in 2 of 12 daily feedings (10.2% group). This pattern of alcohol administration resulted in high peak blood alcohol concentrations with near total clearance. The other artificially reared group was fed a diet made isocaloric to the alcohol-containing diet (gastrostomy control group). Pups were allowed to grow to adulthood and killed on postnatal day 115. The total number of neurons in the inferior olivary nucleus was estimated using unbiased stereological methods. Exposure to alcohol resulted in a significant deficit in the number of neurons in the inferior olive at 115 days of age. The total number of neurons in the alcohol-exposed group was 40.12 +/- 8.7 x 10(3), compared with 53.37 +/- 3.7 x 10(3) in the artificially reared controls. These results indicate that there is a permanent deficit of neurons in the inferior olive after postnatal exposure to alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Early postnatal alcohol exposure acutely and permanently reduces the number of granule cells and mitral cells in the rat olfactory bulb: a stereological study.

This study demonstrates that exposure to alcohol during a period of rapid brain growth can lead to severe and permanent deficits in the number of granule cells and mitral cells in the main olfactory bulb. Sprague-Dawley rat pups were reared artificially and were administered alcohol over postnatal days (PD) 4 through 9, a period of brain development comparable to part of the human third trimester. The daily alcohol dose of 6.6 g/kg was concentrated into two of the twelve daily feedings, producing high peak blood alcohol concentrations followed by near total clearance. Pups were either sacrificed on PD10 or were allowed to grow to adulthood and sacrificed on PD115. The total number of granule cells and mitral cells in the main olfactory bulb were estimated with the aid of unbiased stereological principles and systematic sampling techniques. Exposure to alcohol resulted in significant reductions in the number of both granule cells and mitral cells on PD10. Significant deficits in both neuronal populations remained on PD115. The results support the hypothesis that alcohol exposure can kill developing neurons and lead to permanent neuronal deficits. Substantial developmental changes also occurred in the total number of mitral cells and granule cells between PD10 and PD115 in the control groups. In untreated rats, the number of granule cells increased from 2.20 x 10(6) on PD10 to 5.06 x 10(6) on PD115, while the number of mitral cells decreased from 5.30 x 10(4) to 4.33 x 10(4) over the same time period. These results demonstrate that there is a natural loss of mitral cells during postnatal development at the same time that granule cell number is increasing.

Animals↗
PubMed1988

Quantitative study of granule and Purkinje cells in the cerebellar cortex of the rat.

The numerical densities of granule and Purkinje cells in the cerebellar cortex of the rat were determined by stereological methods. The density of Purkinje cells in our fixed material was 1,018 +/- 39 per mm2 (mean +/- s.e.m.) of Purkinje cell layer and that of granule cells 1.92 +/- 0.03 x 10(6) per microliter of granular layer. The total area of Purkinje cell layer was 332 mm2 and the volume of granular layer was 48 microliters. The rat cerebellum therefore contains 3.38 x 10(5) Purkinje cells and 9.2 x 10(7) granule cells, from which there are 274 granule cells for each Purkinje cell. The density of granule cells and the density of parallel fibers in the molecular layer observed in a companion study indicate that the average length of a parallel fiber is around 5 mm.

Animals↗
PubMed1988

Quantitative study of the Purkinje cell dendritic spines in the rat cerebellum.

The number of spines on an individual Purkinje cell in the cerebellar cortex of the rat was determined by stereological methods. Investigations were based on thin section electron micrographs, freeze fracture replicas, and horseradish peroxidase labeled cells. Purkinje cell dendritic spines in our embedded material had a mean length of 1.4 +/- 0.05 micron and mean neck and head diameters of 0.22 +/- 0.01 micron and 0.45 +/- 0.02 micron, respectively. From these dimensions, an estimate of spine volume in embedded material of 0.132 micron 3 was obtained. The density of dendritic spines in our fixed material was 8.15 x 10(8) or 7.24 x 10(8) per microliters of molecular layer from volume fraction and density per mm2, respectively. The number of spines per linear micron of Purkinje cell spiny branchlet was 17.2 from freeze fracture and 17.6 from horseradish peroxidase labeled dendrites. These all indicate that there are between 154,000 and 175,000 spines on the dendritic tree of each Purkinje cell, considerably more than previously reported for the rat.

Animals↗
PubMed1988

Number of parallel fiber synapses on an individual Purkinje cell in the cerebellum of the rat.

In the present study, stereological techniques applied to electron micrographs of the molecular layer of the rat cerebellum have been used to estimate the number of parallel fiber synapses on the dendritic tree of a single Purkinje cell. Quantitative features of the parallel fiber to Purkinje cell dendritic spine synapses and of the parallel fibers were investigated as a preliminary to estimating the number of synapses. Parallel fiber to Purkinje cell synapses are flattened disclike structures with a mean axial ratio of 14.7 and a mean diameter of 319 microns in fixed tissue. The density of synapses in our fixed material was 8.17 x 10(8) per microliters of molecular layer. Determination of the length density of the synapses per unit area of micrograph indicated a synapse density of 8.03 x 10(8) per microliters. These densities give a total number of synapses per Purkinje cell of 1.74 x 10(5) and 1.71 x 10(5), respectively. Estimation of the number of parallel fiber varicosities and of varicosity length gave a density of 9.31 x 10(8) varicosities per microliters of molecular layer and determining the mean number of parallel fiber to Purkinje cell synapses per varicosity gave a synapse density of 9.82 x 10(8) per microliters, equivalent to 2.09 x 10(5) per Purkinje cell. The reasons why this estimate is likely to be too high are discussed. We conclude that there are some 175,000 parallel fiber synapses on an individual Purkinje cell dendritic tree in the cerebellar cortex of the rat, considerably more than previously reported.

Animals↗