Response of rat cerebral somatostatinergic system to a high ammonia diet

It has been reported that ingestion of an ammonium-containing diet produces hyperammonemia without encephalopathy, thus permitting the study of the specific effects of ammonia toxicity. The present study investigated the rat cerebral somatostatinergic system using this experimental model of hyperammonemia. Wistar rats were fed a high ammonia diet prepared by mixing a standard diet with ammonium acetate (20% w/w); in addition, 5 mM of ammonium acetate was added to their water supply. Control rats were fed with a standard diet. The animals were sacrificed at 3, 7 and 15 days of ammonia ingestion. Ammonia levels in blood had increased ¿3-fold at 7 days of ammonia ingestion. These changes were associated with a significant decrease in the specific binding of somatostatin (SS) to putative receptors sites in the frontoparietal cortex and hippocampus at 7 and 15 days after starting the high ammonia diet. Scatchard analysis shows that the decrease in SS binding resulted from a decrease in the number of available SS receptors rather than a change in receptor affinity. No changes in the somatostatin-like immunoreactivity content (SSLI) were detected in either brain area at the three study times. These results suggest that hyperammonemia alone can affect the rat brain somatostatinergic system. However, the animal model of hyperammonemia used here is insufficient to produce encephalopathy despite the significant increase in serum ammonia

Differential effects of ethanol ingestion on somatostatin content,somatostatin receptors and adenylyl cyclase activity in thefrontoparietal cortex of virgin and parturient rats

Chronic ethanol ingestion decreases the number of somatostatin (SRIF) receptors in the rat frontoparietal cortex and female sex hormones modulate the effects of ethanol in the brain. Therefore, we investigated the differential effects of ethanol consumption on the SRIFergic system in the frontoparietal cortex of virgin and parturient rats given ethanol in their drinking water before and during gestation. In parturient rats, ethanol consumption decreased the density of SRIF receptors (25%, p < 0.01 vs control parturient group) whereas the SRIF-like immunoreactivity (SRIF-LI) content was increased (140%, p < 0.01). In virgin rats, ethanol ingestion decreased the density of SRIF receptors (42%, p < 0.01) more than in alcoholic parturient rats. SRIF-LI levels were unaffected. The inhibitory effect of SRIF on basal and forskolin-stimulated adenylyl cyclase was significantly lower in alcoholic virgin rats as compared to alcoholic parturient rats. No differences in the levels of the G inhibitory (Gi) ¿1 and Gi¿2 proteins were observed among the experimental groups. These results suggest that gestation may confer partial resistance to the ethanol-induced effect on the SRIFergic system

Bone mineral density, body composition, and metabolic health of very low birth weight infants fed in hospital following current macronutrient recommendations during the first 3 years of life

The present study longitudinally evaluated growth, bone mineral density, body composition, and metabolic health outcome in very low birth weight (VLBW) infants whose in-hospital target nutrient intake was within recent recommendations. From six months to three years, bone mineral density (dual-energy X-ray absorptiometry, DXA), body composition, and metabolic health outcome were compared with a reference group of term infants. The aim was to test whether in-hospital achieved weight gain until 36 weeks of gestation (light or appropriate for term equivalent age; LTEA or ATEA) predicts later growth, bone mineral density (BMD), abdominal obesity, or metabolic health outcomes such as insulin resistance, relative to term infants, during the first three years of life. Target in-hospital energy and protein intake was not achieved. Growth in weight, length and head circumference, mid arm circumference, adiposity, fat free mass (FFM), and bone mineralization in VLBW infants was less than those in term infants and influenced by nutritional status at discharge. Preterm infants had poorer motor and cognitive outcomes. Post-discharge body composition patterns indicate FFM proportional to height but lower fat mass index in LTEA preterm infants than term infants, with no evidence of increased truncal fat in preterm infants. The hypothesis of early BMD catch-up in VLBW infants after discharge was not supported by the present data. The clinical significance of these findings is unclear. The data may suggest a reduced obesity risk but an increased osteoporosis risk. Since postnatal growth restriction may have permanent negative health effects, LTEA VLBW infants would especially appear to benefit from targeted preventive interventions. Further follow-up of the infants is required.This research was partially funded by the ‘Fondo de Investigación Sanitaria’ (grant number PI041631

Retinal Molecular Changes Are Associated with Neuroinflammation and Loss of RGCs in an Experimental Model of Glaucoma

Signaling mediated by cytokines and chemokines is involved in glaucoma-associated neuroinflammation and in the damage of retinal ganglion cells (RGCs). Using multiplexed immunoassay and immunohistochemical techniques in a glaucoma mouse model at different time points after ocular hypertension (OHT), we analyzed (i) the expression of pro-inflammatory cytokines, anti-inflammatory cytokines, BDNF, VEGF, and fractalkine; and (ii) the number of Brn3a+ RGCs. In OHT eyes, there was an upregulation of (i) IFN-γ at days 3, 5, and 15; (ii) IL-4 at days 1, 3, 5, and 7 and IL-10 at days 3 and 5 (coinciding with downregulation of IL1-β at days 1, 5, and 7); (iii) IL-6 at days 1, 3, and 5; (iv) fractalkine and VEGF at day 1; and (v) BDNF at days 1, 3, 7, and 15. In contralateral eyes, there were (i) an upregulation of IL-1β at days 1 and 3 and a downregulation at day 7, coinciding with the downregulation of IL4 at days 3 and 5 and the upregulation at day 7; (ii) an upregulation of IL-6 at days 1, 5, and 7 and a downregulation at 15 days; (iii) an upregulation of IL-10 at days 3 and 7; and (iv) an upregulation of IL-17 at day 15. In OHT eyes, there was a reduction in the Brn3a+ RGCs number at days 3, 5, 7, and 15. OHT changes cytokine levels in both OHT and contralateral eyes at different time points after OHT induction, confirming the immune system involvement in glaucomatous neurodegeneration

Acute nicotine administration increases somatostatin content and binding in the rat hypothalamus

Within 4 minutes a single, intravenous injection of nicotine (0.3 mg/Kg) induced increases in somatostatin-like immunoreactivity concentrations in the rat hypothalamus but not in the striatum. These changes were associated with a significant increase in the specific binding of somatostatin to putative receptor sites in hypothalamic membranes, while no significant changes were found in striatum. The enhancement of somatostatin binding resulted from a rapid increase in the number of available receptors rather than a change in receptor affinity. This effect appears to be mediated by nicotinic cholinergic receptors, because pretreatment with a centrally active nicotinic receptor antagonist, mecamylamine (5.0 mg/Kg i.v.), prevented the nicotine-induced changes in somatostatin content and binding in the hypothalamus. Mecamylamine alone had no observable effect on the hypothalamic somatostatinergic system. These results suggest that the rat hypothalamic somatostatinergic system can be regulated by nicotine-like acetylcholine receptors

Effects of acute nicotine and mecamylamine administration on somatostatin concentration and binding in the rat brain

Since nicotine and somatostin have regulatory effects on locomotor activity it was of interest to determine whether the receptors for somatostin are modulated by the cholinergic nicotine-like effects. An i.v. dose of 0.3 mg/kg nicotine induced an increase in the concentrations of somatostatin-like immunoreactivity at 4 min in the parietal cortex and at 15 min in the hippocampus. These changes were associated with a significant increase in the total number of specific somatostatin receptors in the parietal cortex at 15 min and in the hippocampus at 30 min following injection. To determine if the above mentioned changes are related to the nicotine activation of central nicotine-like acetylcholine receptors, a cholinergic nicotinic blocking agent, mecamylamine, was administered before the nicotine injection. Pretreatment with mecamylamine (5.0 mg/kg i.v.) prevented the nicotine-induced changes in somatostatin level and binding in both brain areas. Mecamylamine alone had no observable effect on the somatostatinergic system. These results suggest that the somatostatinergic system can be regulated by nicotine-like acetylcholine receptors and may be involved in some of the behavioral central effects of nicotine

Brain somatostatinergic system at late pregnancy, parturition and the early postpartum period in the rat

During pregnancy and postpartum rats experience a wide varietv of behavioural changes. Since the soma-tostatinergic system has been iraplicated in the control of some of these changes, the present study examined somatostatin (SS) content and specific binding in the frontoparietal cortex and hippocampus of non-pregnant. pregnant (17 to 18 days), parturition and postpartum (10 and 30 days) rats as well as in ovariectomized rats which were or were not treated with estradiol valerianate. The content of somatostatin-like inimunoreactivity (SSLI) was increased at 17 days of pregnancy in frontoparietal cortex and decreased at parturition and 10 days postpartum in that región and the hippocampus under study when compared with SSLI levels in non-pregnant rats. At 30 days postpartum the SSLI content returned to non-pregnant valúes in both brain regions. Scatchard analysis showed that the decrease in [125I]Tyru-SS binding observed at 17 days of pregnancy in the frontoparietal cortex was due to the decrease in the number of SS receptors. In contrast, on the dav of delivery the number of SS receptors in the same brain región increased. The affinity of the SS receptors was consistently unchanged in pregnant and non-pregnant rats in both regions. At 10 days postpartum the valué of specific binding of the tracer to SS receptors in the frontoparietal cortex was not significantly different from that in the non-pregnant rats, although the actual number of receptors was slightly higher. Pregnancy did not change SS binding in the hippocampus. Neither ovariectomy ñor the treatment of ovariectomized rats with estradiol valerianate affected cortical and hippocampal SS content and binding in the rats. These changes in the somatostatinergic system associated with late pregnancy, parturition and the earlv postpartum period may well be important because of their possible role in some of the behavioural changes observed during these periods

Serum gastrin level and gastric somatostatin content and binding in long-term pyloromyotomized children

Since somatostatin inhibits basal and stimulated gastric acid secretion and gastrin release, it is conceivable that decreased gastric somatostatin concentration may be one of the factors responsible for gastric hypersecretion found in patients who have undergone long-term pylorotomy for hypertrophic pyloric stenosis. To investigate this proposal the somatostatin-like immunoreactivity concentration was determined in antral and fundic mucosa samples from control and long-term pyloromyotomized children. In addition, somatostatin binding to cytosol from gastric (fundus and antrum) mucosa and fasting serum gastrin levels and serum gastrin response to a standard breakfast were also studied. The mean fundic and antral somatostatin-like immunoreactivity concentrations were significantly lower in long-term pyloromyotomized children than in control children. The depletion of fundic and antral somatostatin-like immunoreactivity content was associated with an increase in the number of gastric somatostatin binding sites. The fasting serum gastrin levels and serum gastrin response to a standard breakfast (after 60 min) in long-term pyloromyotomized children was significantly higher than those in control children. Since, together with the increase of somatostatin binding to gastric mucosa, there is an increase in the gastrin serum levels, despite the inhibitory effect of somatostatin on gastrin release, the binding capacity cannot be the main factor determining the response to somatostatin in long-term pyloromyotomized children. The present results suggest that both somatostatin and gastrin have some pathophysiologic importance in long-term pyloromyotomized children

The increase in fiber size in male rat gastrocnemius after chronic central leptin infusion is related to activation of insulin signaling

Insulin potentiates leptin effects on muscle accrual and glucose homeostasis. However, the relationship between leptin's central effects on peripheral insulin sensitivity and the associated structural changes remain unclear. We hypothesized that central leptin infusion modifies muscle size through activation of insulin signaling. Muscle insulin signaling, enzymes of fatty acid metabolism, mitochondrial respiratory chain complexes, proliferating cell nuclear antigen (PCNA) and fiber area were analyzed in the gastrocnemius of chronic central infused (L), pair-fed (PF) and control rats. PCNA-positive nuclei, fiber area, GLUT4 and glycogen levels and activation of Akt and mechanistic target of rapamycin were increased in L, with no changes in PF. Acetyl-CoA carboxylase-ß mRNA levels and non-esterified fatty acid and triglyceride content were reduced and carnitine palmitoyltransferase-1b expression and mitochondrial complexes augmented in L. These results suggest that leptin promotes an increase in muscle size associated with improved insulin signaling favored by lipid profile