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Biomedical subjects

T Samorajski

Publications and source records attributed to T Samorajski.

At least 19 recordsLinked to original sources

Synaptic density of caudate-putamen and visual cortex following exposure to ethanol in utero.

Pregnant Long-Evans rats were fed a liquid diet containing ethanol (30% of total calories) during days 3-19 of gestation. Controls were given ad libitum access to liquid diet lacking ethanol, or pair-fed isocaloric amounts based on consumption by the animals in the ethanol group. Brain development of female offspring was evaluated by analysis of electron micrographs of caudate-putamen and visual cortex. Numbers of presynaptic terminals and synaptic junctions (synaptic density) per unit area were compared for 14- and 28-day-old offspring of dams from the three treatment groups. Synaptic density of the caudate-putamen and visual cortex was not affected by ethanol at 14 or 28 days. Although exposure to ethanol during a period comparable to the first two trimesters of human development with minimal or no undernutrition did not affect numerical density of synapses in visual cortex or caudate-putamen, synaptogenesis of caudate-putamen was altered in offspring of pair-fed animals.

Animals↗

Effects of aging and alcohol on the biochemical composition of histologically normal human brain.

Human brains were removed at autopsy and examined grossly and histologically for any abnormality or evidence of disease. Sixty-two brains appearing normal by these criteria were examined further. First, a detailed record of alcohol consumption was obtained. Second, frozen punches of gray and white matter were used to determine the compositional change associated with age and drinking patterns. Increased age was associated with an increase in the water content, particularly in the white matter, a decline in RNA content in gray matter, a decline in total protein in white matter, and a decline in both myelin and the myelin-like subfraction. The loss of myelin membrane in white matter corresponded to a similar increase in water content, although there was an additional loss of some nonmyelin protein. There was no significant shift in the density between the myelin and the myelin-like membranes, and the protein composition of myelin was not significantly altered by age. A history of heavy alcohol consumption was associated with a relative increase in total protein in white matter even though heavy drinking accelerated the age-related loss of myelin. Presumably, alcohol produced a lag in the rate at which nonmyelin proteins are lost or accelerated the accumulation of abnormal protein. Alcohol consumption did not influence the myelin composition or the ratio of myelin and myelin-like membranes. The interval between patient death and autopsy was shown to have little or no effect on the samples used in this study. These data show that normal aging, uncomplicated by other disease processes, can have a significant effect on the composition of brain tissue, particularly the white matter, and that heavy alcohol consumption accelerates degenerative change, even in tissue appearing normal by histology.

Aged↗

Development of axonal-oligodendroglial relationships and junctions during myelination of the optic nerve.

The early stages of myelination were examined in optic nerves of rats aged 12-15 days. The initial association between oligodendroglial processes and bare axons involves no junctional specialization, as the axoglial extracellular space remains unaltered. Following ensheathment by a collar of glial cytoplasm, at least one full rotation of mesaxon was evident before compact myelin formed. Furthermore, myelin was generally evident before a second rotation was completed. In longitudinal sections, an axoglial junction was always observed beginning on the first paranodal loop, continuing through to the last (or outermost) loop. Thus, the formation of myelin and elaboration of a junctional complex in the paranodal region follow a promyelination phase and appear to be synchronous (and possibly related) events. Although the paranodal plasmalemma and axolemma are in close apposition, there is a material in the extracellular space that precipitates phosphotungstic acid, a characteristic that appears to be featured in a number of different types of cell junctions.

Animals↗

Voluntary wheel running exercise and monoamine levels in brain, heart and adrenal glands of aging mice.

The goals of this study were to examine the effects of three months of voluntary wheel-running exercise on life span, whole body and brain, heart and adrenal weights and biogenic amine content (norepinephrine, dopamine, epinephrine and serotonin) in three age groups of male mice. The three groups consisted of mature (9 months), middle-aged (19 months), and old (27-29 months) mice. No significant differences in weight were found between control and exercise or age. The oldest mice had a survival rate of 69% for the exercise group and 43% for the age matched controls when the exercise phase was completed. Locomotor activity was significantly reduced for the old mice compared to the middle-age and mature mice. Only the mature (12 months of age at sacrifice) exercised mice showed a cardiac and adrenal hypertrophy (about 10%). There was a moderate increase in norepinephrine content in the ventral hypothalamus of the brain with exercise (significant at 12 months of age). Biogenic amine content in other regions of the brain (brain stem and forebrain minus hypothalamus) was not affected by age and/or exercise. There was a significant decrease in heart norepinephrine content with exercise in old mice (30-32 months). Adrenal gland norepinephrine content was significantly increased by exercise at 12 months of age and decreased at 22 months of age. Our results suggest that an increase in norepinephrine content in the hypothalamus might be a manifestation of an adaptation to the increased demands upon hypothalamic noradrenergic terminals imposed by prolonged exercise. It is also apparent that aging and exercise alters the amounts of sympathetic transmitter of the heart and adrenal glands. Such alteration may be beneficial to the aging brain by retaining norepinephrine stores that normally decline with age.

Adrenal Glands↗

Prenatal ethanol exposure decreases synaptic density in the molecular layer of the cerebellum.

Pregnant Long-Evans rats were fed a liquid diet containing ethanol during gestation (peak blood ethanol level of 128 mg/dl). Pairfed dams were given isocaloric diet lacking ethanol; and control dams were allowed ad libitum access to liquid diet without ethanol. Subsequent effects of ethanol were measured by morphometric analysis of electron micrographs. Tissue samples from the molecular layer of the cerebellum (sixth lobule) were stained with ethanolic-phosphotungstic acid (E-PTA) and synaptic junctions were counted. Numbers of synaptic junctions per unit area were compared for 14 and 28 day old offspring of ethanol treated, pairfed or control dams. Synaptic density of the molecular layer of the sixth cerebellar lobule was decreased in 28 day old animals which were exposed prenatally to ethanol.

Animals↗

Opiate antinociception is altered by immunemodification: the effect of interferon, cyclosporine and radiation-induced immune suppression upon acute and long-term morphine activity.

It has recently been demonstrated that various forms of immune modification result in a profound attenuation of the opiate withdrawal syndrome. Herein we investigate the extent to which some of the immune modifiers active in withdrawal attenuation affect other opiate related behaviors, namely antinociception and the development of tolerance to this effect. The observations demonstrate that immune modification by cyclosporine and irradiation exposure result in an alteration of the acute antinociceptive effect of morphine; while none of these treatments modify the development of tolerance to this property of morphine.

Animals↗

A morphometric analysis of pyramidal tract structures during postnatal undernourishment and recovery.

Rats were postnatally undernourished during the suckling period (up to 20 days) and the brainstems of the perfused rats were dissected and prepared for electronmicroscopy at 21, 35 and 63 days of age. The effects on myelin were relatively mild and consisted primarily of a slight reduction in the relative numbers of myelinated fibers, most likely caused by a lag in the rate of loss of non-myelinated fibers, and fewer lamellae in myelinated axons of less than 2.5 micron circumference. Organelles were examined in the interfasicular oligodendroglia and in paragigantocellular reticular neurons immediately dorsal to the pyramidal tract. The numbers of mitochondrial particles in neuronal perikarya were significantly increased by postnatal undernourishment, although the numbers of other organelles appeared normal. Increased numbers of mitochondria persisted in nutritionally rehabilitated rats. Mitochondrial particles in oligodendroglia were not altered.

Aging↗

Fetal ethanol exposure: a morphometric analysis of myelination in the optic nerve.

Pregnant Long-Evans rats were fed a liquid diet containing ethanol during gestation. Controls consisted of both pair-fed dams and dams fed ad libitum with an equivalent, iso-caloric diet lacking ethanol. Subsequent effects of ethanol measured in the offspring include a significant lag in the rate at which non-myelinated axons are lost in association with the initial overproduction of neurons. Additionally, there was a slight lag in the rate of acquisition of myelinated axons; and altogether there was a large increase in the ratio of non-myelinated to myelinated axons. Frequency spectra of myelinated and non-myelinated axons by size were normal, and the relationship between axon size and myelin lamellae was also normal. Measured against the dynamic, normal background of rapid cell-loss and the progressive development of myelin, morphometric demonstration and evaluation of the comparatively small divergences associated with fetal alcohol exposure are difficult: nevertheless, these results are consistent with and help account for the marginal hypomyelination previously observed by quantitative neurochemistry.

Animals↗

The corpus callosum during postnatal undernourishment and recovery: a morphometric analysis of myelin and axon relationships.

This study was designed to compare morphometric relationships between myelin lamellae and axons in undernourished and well nourished developing rats, and in rats nutritionally rehabilitated for two weeks. Although sampling techniques employed in this study were not specifically designed to compare numbers of myelinated fibers in test and control populations, we did observe a trend indicating a reduction in the numbers of myelinated fibers. The mean numbers of myelin lamellae, from an average of all myelinated axons, were not different in control and test population. However, regression analysis of axon sizes by numbers of myelin lamellae revealed significant differences from the normal in 21-day-old undernourished rats. For callosal axons of any size, there were too few myelin lamellae in the undernourished rats. A partial recovery was observed in relatively small fibers by 35 days of age, but no recovery was observed in larger sized fibers. Comparison of the frequency distribution of axon circumferences of myelinated fibers revealed an increase in average axonal caliber. Computation shows that although mean numbers of lamellae were not altered by undernourishment, the axons themselves are increased in size by about 10%. This unexpected result indicates that the relationship normally governing the numbers of myelin lamellae is altered by postnatal nutritional deprivation, and that the relatively larger axon calibers do not produce in the ensheathing oligodendroglia any compensatory increase in the layers of myelin.

Animals↗

Effect of exercise on longevity, body weight, locomotor performance, and passive-avoidance memory of C57BL/6J mice.

Studies of human and animal subjects have suggested that exercise may retard aging, help prevent age-related diseases, and prolong life span. Earlier studies focused on the effects of exercise on the heart, skeletal muscles, lungs, metabolism, and longevity. Researchers recently have begun to direct their attention to possible benefits of exercise on the brain. The goals of this study were to examine the effects of voluntary wheel-running exercise on life span, body weight, food and water intake, locomotor performance, and one-trial passive-avoidance memory of mature (10-14 month), middle-aged (20-24 month), and old (28-30 month) C57BL/6J male mice. No significant differences in life span, expressed in months, were found between control and exercised mice when exercise was carried out during maturity, senescence, intermittently across both periods, or continuously throughout maturity and senescence. Exercised adult mice maintained body weight compared to adult controls, an effect not apparent in old mice. Locomotor performance was reduced in old mice, and exercise increased performance much more in adult than in old mice. In the passive avoidance test of recent memory, exercise significantly increased latency, that is, it improved retention, in adult, middle-aged, and old mice. The effect was greatest in middle-aged, next in old, and lowest in adult mice. The findings indicate that exercise may be an important modulator of the rate of aging.

Aging↗

Intracellular translocation of myelin proteolipid protein.

Brainstem slices prepared from 22-day-old rats were employed to study the intracellular translocation of radioactively labeled myelin proteolipid protein (PLP). Double-isotope and short pulse-chase procedures allowed us to demonstrate the flux of PLP through nine different subcellular membrane fractions that were isolated on the basis of their particle size and buoyant density. Tagged PLP was rapidly depleted from microsomes, showed transient passage through a number of presumably intermediate membranous pools, and accumulated in myelin. On the basis of the kinetics of PLP labeling and isotope ratios, the membranes can be arranged as they participate in the intracellular translocation of PLP and consistently show a pattern indicating possible precursor-product relationships.

Animals↗

Myelination of the rat optic nerve during postnatal undernourishment and recovery: a morphometric analysis.

Newborn rats were undernourished from the second postnatal day through 20 days of age and weaned to a diet of laboratory chow ad libitum. Optic nerve development was examined by various light and electron microscopic techniques at 14, 21, 35 and 63 days of age. The degree of undernourishment achieved resulted in body growth lag comparable to results obtained in our previous studies. Although cellularity (cells per photomicrograph area) of the oligodendroglia was unaffected, there was an apparent significant relative reduction in the total number of myelinated fibers by 21 days of age, as determined by light microscopic sampling. Ratios of unmyelinated-to-myelinated fibers were thus estimated by electron microscopy, and results indicated an early increase in the ratio (14 days). Either as the result of catch up in a developmental lag, or as a result of possible restorative effects of rehabilitation, these differences were significant by 35 days of age. The relationship between axon circumference and numbers of myelin lamellae was determined by regression analysis, which revealed a significant reduction in numbers of lamellae over axons of all sizes at 14 days. By 21 days, only fibers in the size range of 1-2 micron of circumference showed a difference, and by 35 days there were no significant differences. These results all indicate that there is a significant myelin reduction in optic nerve of the undernourished rat.

Aging↗

Regional analysis of neostriatal cholinergic and dopaminergic receptor binding and tyrosine hydroxylase activity as a function of aging.

Tyrosine hydroxylase (TH) activity, as well as dopaminergic and cholinergic muscarinic receptor binding were measured in discrete regions of the neostriatum of rats 7, 17, and 27 months old. Activity of TH was highest in the rostral neostriatum as compared to the caudal region. Age-related differences in TH were detected in only one region. The density of dopamine receptors was also highest in the rostral neostriatum of all age groups, but there were no significant age-related differences. The distribution of cholinergic muscarinic receptor binding was similar to that of TH and dopaminergic receptors, and showed age-related changes in discrete regions. These results, when considered with previous data, suggest that in selected striatal regions in the Sprague Dawley rat the cholinergic system is more vulnerable than the dopaminergic system to aging effects.

Aging↗

High-affinity uptake of neurotransmitters in rat neostriatum: effects of aging.

High-affinity uptake of dopamine (DA), glutamate, and gamma-aminobutyric acid (GABA) was determined in crude synaptosomal preparations from neostriatal regions of rats 7, 17, and 27 months of age. Dopamine uptake was highest in rostral neostriatum, but no age-related differences were detected. On the other hand, the high-affinity uptake of both GABA and glutamate was increased with age. This may reflect astrocytic hypertrophy or hyperplasia, which have been reported to occur in the neostriatum during the aging process.

Aging↗

Age-related changes in rat brain capillaries.

We have measured several morphological parameters by electron microscopy of the frontal cortex (FC) and hippocampal CA1 (HC) capillaries in male Fischer 344 rats 3-, 9- and 24-months old. The results indicate that with increasing age there is an increase in the cross-sectional area of the basement membrane, increase in the fraction of endothelial cell and pericyte cytoplasmic area occupied by mitochondria in the FC, increase in the size of the pericyte mitochondria in both the FC and HC, increased capillary lumen area in the FC and decreased capillary lumen area in the HC. Also, the cytoplasmic area occupied by mitochondria in capillary pericytes is larger than in the endothelial cells of both FC and HC. These results suggest that there is regional variation in the age-associated changes in capillary morphometrics.

Aging↗

The synthesis of myelin and brain subcellular membrane proteins in the offspring of rats fed ethanol during pregnancy.

Pregnant Long-Evans rats received either: (1) liquid diet containing 5.15% ethanol; (2) liquid diet pair fed to (1) for total calories; or (3) liquid diet ad libitum. These special diets were administered from the 5th through the 18th days of gestation. Dams received standard laboratory chow and water ad libitum before and after the test interval. Additional dams received standard chow and water throughout the study. Birth weights of offspring in the ethanol group were lower than for offspring of the pair-fed or control groups, and their subsequent growth lagged behind the other groups. Neonate deaths in the ethanol group outnumbered other deaths. Eye opening was delayed, and brain weights appeared low from 16 to 30 days postnatal age, The onset of myelin synthesis was delayed by several days; however, by 30 days of age, the rate of myelin synthesis and net accumulation was comparable to the offspring of pair-fed controls. Thus, the effect of ethanol on brain myelination in the offspring of subject females appears as a delay in myelin initiation and cannot be fully explained by caloric undernourishment. An unexpected observation involved offspring of females fed standard chow throughout the study. The brain myelin concentration in this group was lower than for any of the other groups, which may relate to the higher fat content of the liquids diets and/or the comparatively slow weight gain of pregnant rats on standard chow.

Animals↗