Possible role of GABA in the development of tolerance to alcohol

Summary Rat cerebellar GABA levels were reduced following 2 weeks alcohol administration. Animals also exhibited alcohol tolerance with an air righting reflex. This tolerance was mimiced by picrotoxin administration in control animals and was reduced in animals chronically administered alcohol by aminooxyacetic acid.This work was supported in part by a grant awarded under Public Law 93-282, Division of Addiction Services, Indiana Department of Mental Health, Indianapolis, Indiana, USA, Patrick J. V. Corcoran, M. D., principal investigator.     

Effects of altered thyroid state on the inhibition produced by locus coeruleus in purkinje cells in the rat

Summary The number of cerebellar Purkinje cells inhibited after locus coeruleus stimulation was found to be greater in hyperthyroid rats than in control healthy animals; these in turn showed a higher percentage of inhibited cells than hypothyroid rats. It is concluded that thyroid hormone is capable of modulating synaptic activity in the LC-PC pathway.     

Neuronal cell deficits following maternal exposure to methadone in rats

Summary Rat offspring were maternally subjected to methadone hydrochloride during gestation or lactation. At 21 days of age, the area of the pyramis (cerebellar lobule VIII) in prenatally and postnatally exposed groups was reduced 45% and 36%, respectively, from control levels, and the total number of internal granule neurons/section was reduced 49% and 46%, respectively; the number of granule neurons/mm² in both groups was 75% of control values. Based on histological evaluation the timetable of cerebellar morphogenesis was unaltered in rats prenatally exposed to methadone, suggesting a permanent neuronal deficit, but cerebellar development was markedly delayed in animals subjected postnatally.This work was supported by National Institute on Drug Abuse grant DA-01618.     

Fecundity of the blood-feeding insectRhodnius prolixus increases in successive periods of egg production

The fecundity of the blood-feeding insect,Rhodnius prolixus, was observed to increase in successive periods of egg production, each period being triggered by a single large blood meal. As previously published, the fecundity of mated animals was significantly higher than that of unmated animals for the first period of egg production. For a second period of egg production, fecundity increased significantly in both mated and unmated animals. By the fourth period, fecundity had returned to first-feed values for mated animals, but remained high for unmated animals, and the fecundity of mated and unmated animals was not significantly different. Thus, during successive periods of egg production, the processes which maintain fecundity of unmated animals below that of mated animals are overcome.     

Serotonin metabolism in the CNS in cerebellar ataxic mice

The metabolism of 5-hydroxytryptamine (5-HT) in the CNS was investigated in four kinds of morphologically different ataxic mice; reeler, staggerer, weaver and Purkinje cell degeneration mutants, and in hypocerebellar mice experimentally produced by injection of cytosine arabinoside. 5-HT and 5-hydroxyidoleacetic acid concentrations and tryptophan hydroxylase (TrpOH) activity were measured in the cerebrum, cerebellum and brain stem, respectively. TrpOH activity was significantly reduced only in the reeler mouse. The enhancements of the cerebellar 5-HT metabolism observed in the ataxic mice other than the reeler were supposed to be pseudo-enhancements subsequent to the cerebellar hypoplasia.     

Molecular and cellular basis of small- and intermediate-conductance, calcium-activated potassium channel function in the brain

Small conductance calcium-activated potassium (SK or K_Ca2) channels link intracellular calcium transients to membrane potential changes. SK channel subtypes present different pharmacology and distribution in the nervous system. The selective blocker apamin, SK enhancers and mice lacking specific SK channel subunits have revealed multifaceted functions of these channels in neurons, glia and cerebral blood vessels. SK channels regulate neuronal firing by contributing to the afterhyperpolarization following action potentials and mediating I_AHP, and partake in a calcium-mediated feedback loop with NMDA receptors, controlling the threshold for induction of hippocampal long-term potentiation. The function of distinct SK channel subtypes in different neurons often results from their specific coupling to different calcium sources. The prominent role of SK channels in the modulation of excitability and synaptic function of limbic, dopaminergic and cerebellar neurons hints at their possible involvement in neuronal dysfunction, either as part of the causal mechanism or as potential therapeutic targets. Received 23 April 2008; received after revision 29 May 2008; accepted 4 June 2008     

Acid-base homeostasis and the thyro-parathyroid glands]

Chronic metabolic acidosis entails hyperparathyroidism and osteopathy. In order to elucidate the role of the thyroparathyroids in this bone lesion production the effects of acidic diet for 7 weeks were studied in parathyroidectomized (PTX), thyroparathyroidectomized (TPTX) and shamoperated (Sh-O) growing rats. In all animals urinary excretion of calcium, phosphate, ammonium and titrable acidity was similarly increased. The rise in hydroxyproline excretion and urinary 85-sr (that was injected previous to acidic feeding) was more marked in PTX and TPTX rats. Moreover, in these animals the serum calcium level was increased, the blood pH was decreased. According to these data, an acidic diet intake that is not sufficient to elicit a fall in blood pH of normal young rats can induce severe acidosis in chronically parathyroidectomized or thyroparathyroidectomized animals; moreover the bone resorption appears more marked. It is concluded that parathyroids are involved in the extra-cellular fluid defense mechanism against acidosis by a no bone resorptive mechanism. We hypothesize that the parathyroids permit the necessary and adequate supply of bicarbonates by the bone to maintain blood pH homeostasis.     

Shock induces a long-lasting elevation of blood glucose in Aplysia.

Glucose, and not trehalose, was found to be the main blood sugar in Aplysia californica. Changes in blood glucose in response to stress produced by electric shock were measured in blood obtained both from animals dissected within ten minutes of shocking and from catheterized animals at various intervals, up to two and a half hours after the shock. Electric shock increased blood glucose levels. The rise in blood sugar continued as long as two and a half hours after shock.     

Shock induces a long-lasting elevation of blood glucose inAplysia

Glucose, and not trehalose, was found to be the main blood sugar inAplysia californica. Changes in blood glucose in response to stress produced by electric shock were measured in blood obtained both from animals dissected within ten minutes of shocking and from catheterized animals at various intervals, up to two and a half hours after the shock. Electric shock increased blood glucose levels. The rise in blood sugar continued as long as two and a half hours after shock.     

Variations au cours de la journée de l'incorporation in vivo de la leucine tritiée dans les protéines du cervelet et du cerveau du jeune rat normal et hypothyro?dien. Daily variations of the in vivo [3H] leucine incorporation into the cerebellar and cerebral proteins of the normal and hypothyroid young rat [(author's transl)

In the normal and hypothyroid 6-day-old rat, the specific radioactivity (RSA) and the relative RSA (ratio of the RSA to the [3H] lecine concentration of the acido soluble phase) of the cerebral and cerebellar proteins, changes during the day synchronally. They show a maximum at 15.00 h and a minimum at 0.300 h. At all stages studied, these values are significantly lower in the hyothyroid animals than in normal ones.     

The performance of the octopus circulatory system: A triumph of engineering over design

Summary Despite the very considerable difficulties presented by the basic molluscan anatomy and the possession of a blood pigment with an oxygen carrying capacity that never exceeds 4.5 vols%, the cephalopod circulatory system contrives to deliver oxygen at a rate fully comparable with that of an active fish. This is achieved by adding accessory pumps to push blood through the gills, by a multiplicity of pulsatile veins and by raising the systemic blood pressure considerably above the levels found in other molluscs. Detailed control of blood distribution is a necessity in a system where the peripheral resistences may be expected to change dramatically when the animal starts to move and large parts of the central nervous system are apparently dedicated to this task. In this account we have reviewed blood pressure and flow at rest and in exercise. We have further examined the evidence which indicates how the animals modulate the cardiac output, drawing attention to the very different response found in cephalopods and the higher vertebrates.     

Organization of the mammalian red nucleus and its interconnections with the cerebellum

Summary The red nucleus in monkeys and rats consists of a magnocellular, rubrospinal portion which receives its cerebellar information from the nucleus interpositus, and a parvocellular, rubroolivary portion which receives cerebellar afferents from the nucleus lateralis. Distinct interpositorubrospinal and dentatorubroolivary projections are therefore common to these 2 species.     

Organization of the mammalian red nucleus and its interconnections with the cerebellum.

The red nucleus in monkeys and rats consists of a magnocellular, rubrospinal portion which receives its cerebellar information from the nucleus interpositus, and a parvocellular, rubroolivary portion which receives cerebellar afferents from the nucleus lateralis. Distinct interpositorubrospinal and dentatorubroolivary projections are therefore common to these 2 species.     

Variations au cours de la journée de l'incorporation in vivo de la leucine tritiée dans les protéines du cervelet et du cerveau du jeune rat normal et hypothyroïdien

Summary In the normal and hypothyroid 6-day-old rat, the specific radioactivity (RSA) and the relative RSA (ratio of the RSA to the [³H] leucine concentration of the acido soluble phase) of the cerebral and cerebellar proteins, change during the day synchronally. They show a maximum at 15.00 h and a minimum at 03.00 h. At all stages studied, these values are significantly lower in the hypothyroid animals than in normal ones.     

Cerebellar decussation of fibres from the nucleus reticularis tegmenti pontis in the brain of the albino rat

Summary The existence of a cerebellar decussation of fibres from the medial portion of each nucleus reticularis tegmenti pontis (Rtp) of the albino rat is indicated. Definite cell loss in the medial aspect, of the most rostral third of Rtp is detectable after cerebellar hemisection involving parts or the entire depth of sublobule VIb. Cell loss in the medial aspect of the caudal half of Rtp is evident as a consequence of experimental lesions which damage both sublobules IIb and III.This work was supported by the Medical Research Council of New Zealand.Acknowledgments. A. special acknowledgment to. Mrs Heather Reid for her excellent preparation of the histological specimens. Grateful thanks to Mrs Maureen Owen for her careful typing assistance.     

Abortive effect of autologous anti-alpha-fetoprotein antibodies in the rat]

Female Commentry Rats 80--85 days old, were immunized by 5 intramuscular injections of Mouse alphafetoprotein (AFP) and then mated. After fertilization a supplementary injections was administered. The animals were bled at different times and killed immediately after the last bleeding on the 19 or 20th day of gestation. Titers of AFP and of autologous anti-AFP antibodies in the maternal blood were determined as well as the AFP concentration in the pooled amniotic fluids from live embryos of each litter. Compared to non-immunized control series, the total of live and dead embryos per litter in animals immunized with Mouse AFP showed no difference. However, the number of live embryos was on the average 50% lower than that in the control series. The serum titers of AFP and of antibodies to autologous AFP in immunized pregnant Rats bearing dead embryos decreased concomitantly with the number of live embryos. The results reported herein demonstrate that the presence of anti-autologous AFP antibodies in pregnant Rats correlates with the interruption of development in a significant proportions of embryos. This suggests that certain spontaneous abortions in the Rat and perhaps in other mammals can be explained by the rupture of immunological tolerance to autologous AFP.     

Differential roles of multiple adhesion molecules in cell migration: granule cell migration in cerebellum

The migration of cerebellar granule cells from the external granular layer to the internal granular layer is mediated by the radical Bergmann glial fiber. Recent works have shown that cell adhesion molecules, extra-cellular matrix proteins and proteolytic enzymes or their activators are involved in this process. Immuno-localization studies showed differential temporal and spatial expression patterns of different adhesion molecules, their isoforms, and post-translational modification during different stages of granule cell migration. Functional perturbation experiments using cerebellar explant cultures demonstrated that several adhesion molecules as well as plasminogen activator are involved in granule cell migration and are required in different stages. Other systems used to study granule cell migration including dissociated microwell cultures and granule cell deficient mouse mutants are discussed in the context of adhesion molecules. The results accumulated so far suggest that the migration of granule cells is a complex process in which the cooperation of a group of molecules with different functions, some for adhesion some for de-adhesion, are required to fulfill the different needs during the migratory course.     

Differential roles of multiple adhesion molecules in cell migration: Granule cell migration in cerebellum

Summary The migration of cerebellar granule cells from the external granular layer to the internal granular layer is mediated by the radial Bergmann glial fiber. Recent works have shown that cell adhesion molecules, extra-cellular matrix proteins and proteolytic enzymes or their activators are involved in this process. Immuno-localization studies showed differential temporal and spatial expression patterns of different adhesion molecules, their isoforms, and post-translational modification during different stages of granule cell migration. Functional perturbation experiments using cerebellar explant cultures demonstrated that several adhesion molecules as well as plasminogen activator are involved in granule cell migration and are required in different stages. Other systems used to study granule cell migration including dissociated microwell cultures and granule cell deficient mouse mutants are discussed in the context of adhesion molecules. The results accumulated so far suggest that the migration of granule cells is a complex process in which the cooperation of a group of molecules with different functions, some for adhesion some for de-adhesion, are required to fulfill the different needs during the migratory course.     

Cerebral ammonia production during hypoglycemia in the newborn calf.

The effect of insulin hypoglycaemia on cerebral blood flow, and cerebral metabolic rates of glucose, oxygen and ammonia was investigated in the unanaesthetized newborn calf. A net loss of ammonia from the brain occurred during hypoglycaemia, and was greater in convulsing than in comatose animals.     

Physiological effects of the meteorologically abnormal year 1974 observed in healthy males in the Netherlands and southern Norway.

Convincing evidence of biological effects during long-term abnormal weather conditions is very rare because usually no continuous series of physiological data from the same animals or humans (either single or in groups) have been collected over many years during the period preceding the meteorological event. Since 1955, at the Biometeorological Research centre, Leiden, about 220,000 blood data were collected from healthy male blood donors at Leiden, The Netherlands, and about 110,000 data at Oslo, Norway, since 1966. It was found that during the meteorologically abnormal year of 1974, which was abnormal in many parts of the world, both in Leiden and Oslo abnormal biological patterns occurred in blood sedimentation rate, haemoglobin, diastolic blood pressure, gamma-globulin levels, Piccardi p-test percentages and a few other biological parameters. A more complete monograph will be published at a later date.