Selenium in the anterior pituitary of the rat after a single injection of75Se sodium selenite

In order to investigate the selenite metabolism in the anterior pituitary and compare it with other endocrine organs, rats were injected intraperitoneally with⁷⁵Se sodium selenite (5 mg/kg). The rats were whole body counted shortly after injection and recounted just before sacrifice, which was performed 2, 24, 48 h, and 4, 10, 20, 30, 40, 60, and 80 d after injection. Besides the anterior pituitary, the selenium content was also estimated in the thyroid gland, testis, adrenals, liver, kidney, and blood. The maximum selenium content was observed in all organs 2 h after injection, at which time the anterior pituitary contained 2.9 μg/g wet wt, compared to 13.5 μ/g wet wt in liver and .6 μg/mg wet wt in testis. The excretion of selenite from the anterior pituitary resembled that seen in most other organs investigated, i.e., an initial rapid excretion and a slower secondary phase resembling a first order reaction. Practically all selenium was excreted by 60 d after injection.     

Bombesin affects the central nervous system to produce hyperglycemia in rats

Bombesin, a peptide isolated from frog skin, acts through the central nervous system to produce hyperglycemia in rats. Bombesin induced hyperglycemia may be mediated via adrenomedullary-catecholamine induced changes in insulin and glucagon secretion resulting in enhanced hepatic glucose output.     

Uptake of 75-selenium into the central nervous system of the rat

These experiments have investigated selenium movement between blood and the CNS in anaesthetized rats. Each animal was anaesthetized and the left femoral blood vessels cannulated for blood withdrawal and solute infusion. Each rat received 75-Se as sodium selenite infused in normal saline and experiments lasted between 5 minutes and 5 hours during which blood samples were periodically taken. At termination, the CNS was removed, dissected and analysed with the plasma samples for 75-Se radioactivity by -counting. Data were analyzed by multiple-time uptake analysis. Results showed unidirectional uptake of 75-Se into the CNS and some regional differences were found. On average the CNS influx rate constant (K_in) was about 7±1×10^–5 ml/min/g. This indicates that the 75-Se most likely entered the CNS in a protein-bound form.     

Actions of sodium valproate on the central nervous system.

The branched chain fatty acid, valproate, has a number of distinct pharmacological effects on the central nervous system. In experimental animals it showed clear anticonvulsant activity, an observation which led to its major clinical use as an antiepileptic agent, especially in petit mal seizures. More recently, valproate has shown its usefulness in treating mood disorders and migraine headaches. The basis for its clinical efficacy might be related to its ability to enhance central GABAergic neurotransmission or perhaps to its inhibition of Na+ channels. Whether each of the distinct therapeutic effects of valproate has the same molecular basis is not known.     

Selenium complexes in the anterior pituitary of rats exposed to L-selenomethionine

Selenium precipitates were demonstrated histochemically by silver amplification at light and electron microscopic levels in the anterior pituitary of rats exposed to L-selenomethionine (SeMeth). By electron microscopy (EM), the silver amplified selenium complexes were identified in somatotrophs, corticotrophs and gonadotrophs. Precipitates were observed mainly in the secretory granules and to a lesser extent in the lysosomes. The staining intensity increased with increasing amounts of SeMeth. Following a single injection of 3.7 mg Se/kg a substantial increase in staining was observed during the first 48 h after injection and precipitates could still be observed in the anterior pituitary after 2 weeks. During a long-term study where the rats were exposed to selenium contained in the drinking water (3.0 mg Se/l drinking water for 1, 2 or 4 weeks) an increasing amount of precipitates were observed during the first 2 weeks followed by a small decrease in staining intensity. Organic selenium, or rather a metabolite, is suggested to form bands with endogenous metal, primarily zinc, as has been suggested in the brain and anterior pituitary after exposure to sodium selenite.     

Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats chronically exposed to 836 MHz modulated microwaves.

We have tested an 836.55 MHz field with North American Digital Cellular (NADC) modulation in a 2-year animal bioassay that included fetal exposure. In offspring of pregnant Fischer 344 rats, we tested both spontaneous tumorigenicity and the incidence of induced central nervous system (CNS) tumors after a single dose of the carcinogen ethylnitrosourea (ENU) in utero, followed by intermittent digital-phone field exposure for 24 months. Far-field exposures began on gestational day 19 and continued until weaning at age 21 days. Near-field exposures began at 35 days and continued for the next 22 months, 4 consecutive days weekly, 2 h/day. SAR levels simulated localized peak brain exposures of a cell phone user. Of the 236 original rats, 182 (77%) survived to the termination of the whole experiment and were sacrificed at age 709-712 days. The 54 rats (23%) that died during the study ("preterm rats") formed a separate group for some statistical analyses. There was no evidence of tumorigenic effects in the CNS from exposure to the TDMA field. However, some evidence of tumor-inhibiting effects of TDMA exposure was apparent. Overall, the TDMA field-exposed animals exhibited trends toward a reduced incidence of spontaneous CNS tumors (P < 0. 16, two-tailed) and ENU-induced CNS tumors (P < 0.16, two-tailed). In preterm rats, where primary neural tumors were determined to be the cause of death, fields decreased the incidence of ENU-induced tumors (P < 0.03, two-tailed). We discuss a possible approach to evaluating with greater certainty the possible inhibitory effects of TDMA-field exposure on tumorigenesis in the CNS.     

Selenium metabolism in rats after administration of toxic doses of selenite

We studied organ concentration, excretion and excreted forms of selenium in young and adult rats after a single s.c. injection of a sublethal dose of 75Se-selenite. In the young about a 10-fold higher concentration of 75Se in blood, liver, kidneys and In the young, about a 10-fold higher concentration of 75Se in blood, liver, kidneys and heart was found at all the experimental intervals studied (1-7 days). The highest 75Se concentration in the young was in the liver while in the adults it was found in the kidneys. The spectrum of radioselenium metabolites in the urine was the same in both groups. However, the main product excreted by young rats was 75Se-glutathione selenotrisulphide and an unidentified neutral substance while it was the trimethylselenonium ion in the adults. Ontogenetic differences in selenium metabolism could be one of the factors underlying the differences in the response of the young and the adult rats to toxic doses of selenite.     

Tyrosinase-like polypeptides in the uterus and in the central nervous system of rats.

Nuclear and cytosolic fractions of rat uteri and tissues from the central nervous system contain proteins that are recognized by a polyclonal tyrosinase antibody. This antibody eliminates the cresolase activity of uterine nuclear extract when estradiol is used as substrate. Thus, it appears that tyrosinase-like proteins might be present in tissues not generally considered to chain such an enzyme.     

Neuroprotective effect of mexiletine in the central nervous system of diabetic rats

Both experimental and clinical studies suggests that oxidative stress plays an important role in the pathogenesis of diabetes mellitus type 1 and type 2. Hyperglycaemia leads to free radical generation and causes neural degeneration. In the present study we investigated the possible neuroprotective effect of mexiletine against streptozotocin-induced hyperglycaemia in the rat brain and spinal cord.30 adult male Wistar rats were divided into three groups: control, diabetic, and diabetic-mexiletine treated group. Diabetes mellitus was induced by a single injection of streptozotocin (60 mg/kg body weight). Mexiletine (50 mg/kg) was injected intraperitoneally every day for six weeks. After 6 weeks the brain, brain stem and cervical spinal cord of the rats were removed and the hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for biochemical analysis (the level of Malondialdehide [MDA], Nitric Oxide [NO], Reduced Glutathione [GSH], and Xanthine Oxidase [XO] activity). MDA, XO and NO levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the diabetic group increased significantly, when compared with control and mexiletine groups (P < 0.05). GSH levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the diabetic group decreased significantly when compared with control and mexiletine groups (P < 0.05).This study demonstrates that mexiletine protects the neuronal tissue against the diabetic oxidative damage.     

Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO₂) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO₂ with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO₂ on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO₂, at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO₂ alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.     

Endocannabinoids in the central nervous system

The major psychoactive component of cannabis derivatives, delta9-THC, activates two G-protein coupled receptors: CB1 and CB2. Soon after the discovery of these receptors, their endogenous ligands were identified: lipid metabolites of arachidonic acid, named endocannabinoids. The two major main and most studied endocannabinoids are anandamide and 2-arachidonyl-glycerol. The CB1 receptor is massively expressed through-out the central nervous system whereas CB2 expression seems restricted to immune cells. Following endocannabinoid binding, CB1 receptors modulate second messenger cascades (inhibition of adenylate cyclase, activation of mitogen-activated protein kinases and of focal-adhesion kinases) as well as ionic conductances (inhibition of voltage-dependent calcium channels, activation of several potassium channels). Endocannabinoids transiently silence synapses by decreasing neurotransmitter release, play major parts in various forms of synaptic plasticity because of their ability to behave as retrograde messengers and activate non-cannabinoid receptors (such as vanilloid receptor type-1), illustrating the complexity of the endocannabinoid system. The diverse cellular targets of endocannabinoids are at the origin of the promising therapeutic potentials of the endocannabinoid system.     

Insulin and the central nervous system

Data from literature concerning the neurobiological, electrical and metabolic effects of insulin are reviewed. Emphasis is laid on insulin distribution in the CNS, on distribution and localization of the insulin brain receptors, on insulin transport through the hemato-encephalic barrier. Data concerning insulin effect on the electrical activity of various CNS neurons, particularly, on those of the feeding and satiety centres. The effects of insulin on the brain metabolism are discussed. Insulin shares many properties with the nerve growth factor and may be considered as specific neurotransmitter and neuromodulator.     

Emergence in the central nervous system

“Emergence” is an idea that has received much attention in consciousness literature, but it is difficult to find characterizations of that concept which are both specific and useful. I will precisely define and characterize a type of epistemic (“weak”) emergence and show that it is a property of some neural circuits throughout the CNS, on micro-, meso- and macroscopic levels. I will argue that possession of this property can result in profoundly altered neural dynamics on multiple levels in cortex and other systems. I will first describe emergent neural entities (ENEs) abstractly. I will then show how ENEs function specifically and concretely, and demonstrate some implications of this type of emergence for the CNS.     

Calcitonin gene-related peptide-like immunoreactivity in the central nervous system and peripheral organs of rats

The concentrations of rat calcitonin gene-related peptide-like immunoreactivity (rCGRP-LI) in various organs of male rats as well as the molecular heterogeneity of rCGRP-LI in tissue extracts was examined using a specific radioimmunoassay (RIA) for rCGRP and gel-filtration chromatography. rCGRP-LI was high in extracts of the spinal cord (202 +/- 22.6 pg/mg wet wt. of tissue; mean +/- S.E.M.) and of the thyroid (229 +/- 62.3 pg/mg). rCGRP-LI was detectable in the brainstem, hypothalamus, stomach, duedenum, pancreas and kidney. The elution pattern of the extracts on a Sephadex G-50 column showed 3 peaks of rCGRP-LI irrespective of organs and tissues. The first peak corresponded to authentic rCGRP-(1-37). The second and third rCGRP-LI peaks probably consisted of C-terminal fragments of rCGRP, because they had a lower molecular weight than rCGRP-(1-37) and because our antiserum cross-reacts with a synthetic C-terminal fragment. The ratio of 3 rCGRP-LI molecules, however, differed between neural tissue extracts and others. The main component of rCGRP-LI in neural tissue was authentic rCGRP-(1-37), while the smaller fragments of rCGRP were chiefly contained in other tissues like the stomach, pancreas and thyroid. The relative ratio of rCGRP-LI molecules with different size in respective tissue extracts was not changed after leaving the dissected tissues for 2 h at room temperature. These findings indicate that rCGRP-LI is abundantly present in the thyroid as well as the spinal cord and it is detected in lower amounts in the alimentary tract and central nervous system. rCGRP-LI in the extracts consists of 3 different components, the proportions of which vary from one tissue to another, probably reflecting tissue-specific differences in the processing of CGRP.