Reparative changes in the sensorimotor cortex of the offspring in moderate prenatal alcoholism]

Sensorimotor cortex of 21-, 30-, 60-day-old offspring given prenatally moderate alcohol (2 g/kg) manifested signs of compensatory type: double nerve and glial cells, open capillaries, nearby nerve and glial cell bodies with basal membrane of capillaries. Intracellular reparative processes in dystrophic neurons were observed: nuclear activation, hyperplasia of cytoplasmic organelles, hypertrophy of some of them. Reparative processes are more distinct in 30-day-old rat offspring In 60-day-old offspring a polymorphic pattern of cortical synapses ultrastructure was found. However, dystrophic changes of neurons and interneuronal connections still remain.     

Ultrastructure of sensorimotor cortex neurons in the progeny of rats receiving alcohol during pregnancy

Dynamics of ultrastructural changes in the sensomotor cortex neurons has been studied on the 21st, 30th and 60th days of life in offspring born by the rats given 20% alcohol (2 g/kg) during pregnancy. Moderate antenatal alcoholization produces certain disturbances in the ultrastructure of the cortical neurons and their dendrites. This is manifested as presence of retardation signs in maturation of nervous cell populations, as dystrophic changes in the neurons and their dendrites and display of reparative character with their own dynamics in the postnatal period of ontogenesis. The first two categories of the ultrastructural changes in the cortical neurons are more manifested at early stages of the postnatal development of the offspring, and the reparative processes--at the age of two months. Despite the presence of the reparative shifts, the dystrophic changes of the neurons of hypoxic character are present up to the period of sexual maturation. This demonstrates that the antenatal alcoholic intoxication in the offspring is manifested in the postnatal ontogenesis for a long time.     

Morphofunctional evaluation of the condition of the brain in rats with different degrees of recovery of neurological status following arrest of systemic blood circulation

The brain status was studied for four days after resuscitation of rats with different degrees of recovery of the neurological status after systemic circulatory arrest induced by the occlusion of vascular bundles of the heart. Morphometric analysis of the population of Purkinje cells from the two different functional zones of the cerebellum revealed that in comparison with completely recovered rats, the animals with disturbed neurological status were characterized by loss of neurons, disturbed composition of the neuronal population, development of severe dystrophic cell changes. The lateral zone of the cerebellum hemisphere was most affected. Four days after resuscitation all the animals showed a sharp increase in the size of the nucleus of Purkinje cells, which is considered to be one of the mechanisms of neuronal adaptation to hypoxia.     

Synaptic changes in cortical and subcortical brain formations in old rats

Electron microscopy was used to study structural changes of synapses in sensorimotor, parietal, limbic cortical areas, hippocamp, blue spot and hypothalamus of old Wistar rats, aged 28-30 months. Polymorphism of ultrastructural changes in neuronal and synapse processes and individual variability of these shifts in the brain of old rats have been revealed. The predominant damage of post-synaptic synapse components with ageing is demonstrated. Along with dystrophic and destructive changes in pre- and post-synaptic parts of the contact, signs of compensatory adaptive resettings in inter-neuronal links have been detected.     

Content of NCAM, the neural cell adhesion molecule, in the brain of rats subjected to prenatal stress

The content of NCAM, the neural cell adhesion molecule, was studied in the cerebral cortex, hippocampus, striatum, cerebellum, and pons of 15- and 30-day-old rats, the offspring of intact females and females subjected to stress during pregnancy. At the 30th day of the postmatal development, opposite NCAM concentration changes were observed in the cortex and other brain parts of the offspring of stressed rats. These differences can be related to a deficiency of mature synapses in the forebrain of prenatally stressed rats and adaptation rearrangements in the neuronal systems of the brainstem and cerebellum.     

The Lateral Hypothalamic Area: Peculiarities of Aging and the Effect of Chronic Electrical Stimulation on the Lifespan in Rats

Age-related morphological and functional changes in the lateral hypothalamic area (LHA) were studied in experiments on young adult (6-8 months) and old (26-28 months) male Wistar rats. It was found that during aging the neuronal density in the LHA decreased, and significant qualitative destructive and dystrophic changes in the neuronal population developed. The background impulse activity of LHA neuronal units, the mass background electrical activity recorded from this structure, and the Na⁺, K⁺-ATPase activity decreased during aging. In old rats, the rate of LHA self-stimulation was lower, and the range of reinforcing current amplitudes, which provided self-stimulation intensity close to the maximum, was narrower than in adult animals. Chronic electrical LHA stimulation in old rats ensured an increase in the lifespan and maximum life expectancy in these animals. In addition, the lifespan positively correlated with the duration of LHA stimulation. It is concluded that lowering of the functional activity of the LHA neural systems is one of the substantial aspects of the aging process, and activation of this structure in old animals by its chronic electrical stimulation can exert a geroprotective effect.     

Changes in red nucleus neuronal development following maternal alcohol exposure

The red nucleus of Swiss Webster mouse fetuses was examined for morphological changes following maternal ethanol exposure. Pregnant females were given a liquid diet containing 30% or 0% ethanol-derived calories. Changes in numerical density of neurons and in neuronal nuclear volume were found in the rostral red (RR) nucleus of ethanol-exposed pups but not in the caudal red (CR) nucleus. Because of the integrative nature of the RR, changes in neuronal morphology that might relate to synaptic connections could affect the behavioral response mechanisms of these offspring.     

Fine structure of islet-cell innervation in the pancreas of normal and alloxan-treated rats

Summary The innervation of the islets of Langerhans of normal albino rats and of albino rats treated with several daily doses of 125 mg/kg of alloxan was studied by electron microscopy. In the normal rat, nerve endings containing either agranular vesicles (200–400 Å) alone or in combination with large granular vesicles (500–800 Å) were found on both alpha and beta cells. Infrequently a third type of nerve ending containing small granular synaptic vesicles could be observed. Bundles of unmyelinated axons were also seen, as were typical autonomic ganglion cells. Similar normal neural elements were noted in rats treated with alloxan. However, islets of alloxan-treated animals also possess large elliptical profiles which appear to be dystrophic nerve terminals. These structures most frequently contact degranulated beta cells. Islets of Langerhans fixed with zinc iodide-osmium (ZIO) reported to specifically impregnate synaptic vesicles were also studied. Synaptic vesicles of normal axons and nerve endings as well as of the dystrophic structures were filled with ZIO reactive material. These studies suggest that alloxan may induce autonomic nerve ending changes in the rat endocrine pancreas. This may result from neuronal hyperactivity in an attempt to secrete insulin from the post-alloxan insulin-depleted beta cell.     

Connective tissue metabolism in muscular dystrophy. Amino acid composition of native types I, III, IV and V collagen isolated from the gastrocnemius muscle of embryonic chickens with genetic muscular dystrophy

The amino acid composition data on types I, III, IV and V collagen isolated from embryonic dystrophic skeletal muscle strongly indicate that alterations in collagen synthesis occur in intramuscular connective tissue of developing muscles in embryonic dystrophic chickens. The changes observed in the amino acid composition of dystrophic collagen were: (a) a selective removal of polar amino acids and substitution with non-polar amino acids; (b) significant decreases in basic (lysine, hydroxylysine and arginine) and hydroxylated (4-hydroxyproline and hydroxylysine) amino acids; and (c) significant increases in the amounts of glycine, proline and alanine. The amino acid substitutions suggest a genetic alteration in the collagen synthesizing process and a change in its structure. The variations in amino acid composition of collagen from dystrophic chickens could give rise to a decrease in both inter- and intramolecular cross-linking, thus decreasing the stability and functionality of newly formed collagen fibrils. The differences associated with the dystrophic collagen reported in this study are probably due to the differences in primary structure in terms of amino acid sequence rather than post-translational modifications. The structural differences noted would also lead to an alteration of the role collagen plays in regulating the differentiation of developing muscles. The changes in amino acid structure strongly suggest that the 'collagen' formed by dystrophic chickens should be considered a collagen-like protein or 'collagenoid'.     

The levels of cyclic GMP and glucose 1,6-diphosphate, and the activity of phosphofructokinase, in muscle from normal and dystrophic mice.

A striking reduction in the levels of glucose 1,6-diphosphate and an increase in cyclic GMP were found in muscle from dystrophic mice. Concomitant to these changes, the allosteric activity of phosphofructokinase was found to be markedly reduced. These findings could offer an explanation for the observed reduction in glycolysis in the dystrophic muscle.     

The levels of cyclic GMP and glucose 1,6-diphosphate,and the activity of phosphofructokinase,in muscle from normal and dystrophic mice

A striking reduction in the levels of glucose 1,6-diphosphate and an increase in cyclic GMP were found in muscle from dystrophic mice. Concomitant to these changes, the allosteric activity of phosphofructokinase was found to be markedly reduced. These findings could offer an explanation for the observed reduction in glycolysis in the dystrophic muscle.     

Hippocampal apoptosis involved in learning deficits in the offspring exposed to maternal high sucrose diets

The hippocampus plays a crucial role in learning and memory, and neuronal apoptosis in the hippocampus contributes to learning deficits. Metabolism problems in pregnancy related to excessive fuel consumption (e.g., high fat, high sugar) may influence cognitive and behavioral functions in the offspring by affecting developing brain cells. This study determined the influence of maternal high sucrose (HS) diets on behavior and hippocampal neurons in the young offspring. The ratio of brain weight to body weight in the offspring exposed to prenatal HS diets was significantly decreased; the Morris water maze showed that the offspring exposed to prenatal HS diets exhibited increased escape latencies and path length during navigation testing, while there were no changes in time spent in the target quadrant and number of target approaches. In the offspring exposed to prenatal HS, TUNEL-positive cells were significantly increased in CA1, CA2 and CA3 of the hippocampus; protein expression of insulin-like growth factor-I, PI3K and phosphorylated Akt was significantly decreased, while caspase-3 and N-methyl-d-aspartate receptors were significantly increased in the hippocampus, and there was no change in expression of Bcl-2 and Akt. The results demonstrated that prenatal HS diets could induce the spatial acquisition deficits in the young offspring associated with hippocampal apoptosis, and altered signaling factors for antiapoptosis in the hippocampus might play a critical role in cognition disorders in young children.     

IGF-II ameliorates the dystrophic phenotype and coordinately down-regulates programmed cell death

Duchenne muscular dystrophy (DMD) is a fatal and crippling disease of skeletal muscle which displays increased fibre turnover and elevated levels of programmed cell death (PCD) in muscle stem cells. Previously we showed that this cell death is inhibited by the growth factor IGF-II. To determine the functional significance of PCD to the dystrophic phenotype, we used a transgene to over-express IGF-II in the mdx mouse. We found that ectopic expression of IGF-II inhibited the elevated PCD observed in skeletal muscles in the absence of functional dystrophin and significantly ameliorates the early gross histopathological changes in skeletal muscles characteristic of the dystrophic phenotype. Replacement of the dystrophin gene abolished abnormal skeletal muscle cell PCD levels in vivo in a dose-dependent manner and in dystrophic SMS cell lines cultured in vitro. Thus elevation of stem cell PCD in dystrophic skeletal muscle is a direct consequence of the loss of functional dystrophin. Together these data demonstrate that elevated skeletal muscle cell PCD is a critical component of dystrophic pathology and is inversely correlated with both dystrophin gene dosage and with muscle fibre pathology. Targeting PCD in dystrophic muscles reduces both PCD and the classical features of dystrophic pathology in the mdx mouse suggesting that IGF-II is a strong candidate for therapeutic intervention in the dystrophinopathies.     

Elevation of calmodulin in avian muscular dystrophy

In an attempt to understand the mechanism of calcium accumulation in myopathies, changes in the major calcium-binding protein, calmodulin, was studied in genetically dystrophic chickens. Measurements by radioimmunoassay revealed an increase in the calmodulin concentration of dystrophic chicken muscles. Poly A-containing RNA(s) of fast and slow muscles from the normal and dystrophic chicks were hybridized with [32P]-labeled calmodulin cDNA probe by the dot-hybridization technique. Densitometric scan of the autoradiogram showed that the calmodulin mRNA levels of dystrophic fast muscles (pectoralis and posterior latissimus dorsi) were approximately two-fold higher than those of the corresponding normal muscles. No significant change in calmodulin and calmodulin messenger RNA of slow muscle (ALD) was found in dystrophic chickens. Our results suggest that increased calcium flux within the dystrophic muscle may be modulated by calmodulin.     

Ultrastructural changes in the cardiomyopathy of dystrophic hamsters and mice

Changes in the ultrastructure of the cardiac muscle cells have been followed in dystrophic mice and hamsters (22-40 weeks of age) and in both species a severe cardiomyopathy accompanies the cellular damage of the skeletal muscle. The degradative changes of the myofilament apparatus of the heart cells and the specific changes in mitochondrial ultrastructure (including swelling, septation and apparent division) are characteristic of the cellular damage of both the dystrophic skeletal muscle and of normal cardiac muscle in which [Ca]i has been experimentally raised, confirming the suggestions that (i) the same gene is responsible for the myopathy of skeletal and cardiac muscle in animal dystrophy and (ii) that changes in [Ca]i are implicated in the degradative changes of muscle cells.     

Change in the concentration of nucleic acids and cAMP in neurogenic dystrophies of the stomach]

There proved to be a reduction of the RNA content in the tissue of the rat stomach in its dystrophic affection induced by traumatization of the duodenum, this pointing to the reconstruction of the cell genetic apparatus under conditions of extreme stimulation. Under the same experimental conditions there was a pronounced decrease of the cAMP level in the gastric mucosa of rabbits. The significance of the changes in the mechanism of the development of destructive and metabolic disturbances in the neurogenic dystrophic affections induced by extreme stimulation is discussed.     

Structural changes in the testis in complete removal of the pancreas and its resection

The dog pancreas was resected completely or partially. The morphofunctional status of the testicle was examined at varying times after operation with the use of histological, histochemical and morphometric tests. The alterations discovered attest to the dependence of the structural shifts in the testicle on the type of surgery on the pancreas. Resection of the end parts caused temporary and insignificant changes in the testis. Resection of the central part with ligation and intersection of the main excretory ducts gave rise to dystrophic changes in the spermatogenic epithelium, disorders in the structural elements responsible for hormonal activity. Complete resection of the pancreas was early in affecting the morphofunctional status of the testicle. Ten to 15 days after operation profound dystrophic and atrophic changes were detectable in all the cells of the testicle. Injection of insulin postponed the animal's death, decelerated but not prevented the development of regressive changes in the testis.