Palatable Food Dampens the Long-Term Behavioral and Endocrine Effects of Juvenile Stressor Exposure but May Also Provoke Metabolic Syndrome in Rats.

The juvenile period is marked by a reorganization and growth of important brain regions including structures associating with reward seeking behaviors such as the nucleus accumbens (NA) and prefrontal cortex (PFC). These changes are impacted by stressors during the juvenile period and may lead to a predisposition to stress induced psychopathology and abnormal development of brain reward systems. Like in humans, adult rodents engage certain coping mechanisms such as increases in the consumption of calorie-rich palatable foods to reduce stress, but this behavior can lead to obesity and metabolic disorders. In this study, we examined whether stressors during the juvenile period led to increased caloric intake when a palatable diet was accessible, and whether this diet attenuated adult stress responses. In addition, we examined if the stress buffering effects produced by the palatable diet were also accompanied by an offset propensity towards obesity, and by alterations in mRNA expression of dopamine (DA) receptors in the NA and PFC in adulthood. To this end, juvenile male Wistar rats underwent episodic stressor exposure (forced swim, elevated platform stress and restraint) on postnatal days (PD) 27-29 and received access to regular chow or daily limited access to a palatable diet until adulthood. At the age of 2 months, rats were tested on a social interaction test that screens for anxiety-like behaviors and their endocrine responses to an acute stressor. Animals were sacrificed, and their brains processed to detect differences in DA receptor subtype expression in the PFC and NA using qPCR. Results showed that rats that were stressed during the juvenile period displayed higher social anxiety and a sensitized corticosterone response as adults and these effects were attenuated by access to the palatable diet. Nevertheless, rats that experienced juvenile stress and consumed a palatable diet showed greater adiposity in adulthood. Interestingly, the same group displayed greater mRNA expression of DA receptors at the NA. This suggests that access to a palatable diet mitigates the behavioral and endocrine effects of juvenile stressor exposure in adulthood, but at the cost of metabolic imbalances and a sensitized dopaminergic system.

Sacred Maya incense, copal (Protium copal - Burseraceae), has antianxiety effects in animal models.

ETHNOPHARMACOLOGICAL RELEVANCE: The Maya have traditionally used copal, Protium copal, as incense during ceremonies since pre-Columbian times. Anecdotally, copal (when burned as incense), is thought to elicit mentally uplifting and calming effects. The main objective of this study was to determine whether the incense elicits anxiolytic-like behavior in animal models using rats. A second objective was to characterize active constituents and discern potential mechanism(s) of action, specifically the involvement of the GABAergic and endocannabinoid (eCB) systems. Despite the extensive Central American use of this resin, there are currently no known scientific behavioral or pharmacological studies done with the incense. MATERIALS AND METHODS: Quantification of the triterpenes in the copal resin and cold trapped incense was achieved by HPLC MS. Behavioral effects in rats were assessed using the elevated plus maze (EPM), social interaction (SI) test, conditioned emotion response (CER) and Novel object recognition (NOR) paradigms. Rats were exposed to burning copal (200 mg) over 5 min in a smoking chamber apparatus and then immediately tested in each behavioral paradigm. Follow-up SI tests were done using two antagonists flumazenil (1 mg/kg) and AM251 (1 mg/kg) administered systemically. Inhibition of MAGL (monoacylglycerol lipase) was measured by microplate assay with recombinant human enzyme and probe substrate. RESULTS: Phytochemical analysis revealed that copal resin and incense had high α- and ß-amyrins and low lupeol triterpene content. Exposure to Protium copal incense significantly reduced anxiety-like behavior in the SI and CER tests. In contrast, no anxiolytic effects were observed in the EPM. The CER effect was time dependent. Both flumazenil and AM251 blocked the anxiolytic activity of copal revealing the involvement of GABAergic and endocannabinoid systems. Copal, as well as the identified triterpenes, potently inhibited monoacylglycerol lipase (MAGL) activity in vitro (IC50 ≤ 811 ng/mL). CONCLUSIONS: This is the first study to show that copal incense from Protium copal elicits anxiolytic-like effects in fear and social interaction models as evidenced by a reduced learned fear behavior and an increase in active social interaction. It's high α and ß-amyrin content suggests behavioral effects may be mediated, in part, by the known action of these terpenes at the benzodiazepine receptor. Furthermore, P. copal's observed activity through the eCB system via MAGL offers a new potential mechanism underlying the anxiolytic activity.

Dose-related effects of chronic resveratrol administration on neurogenesis, angiogenesis, and corticosterone secretion are associated with improved spatial memory retention following global cerebral ischemia.

OBJECTIVES: The polyphenol resveratrol has shown regulatory effects on hippocampal neurogenesis, which according to the neurovascular niche hypothesis, is likely to involve stimulation of angiogenesis. In rodents, global cerebral ischemia leads to selective CA1 neuronal damage, spatial memory impairments, lasting changes in corticosterone (CORT) secretion, and increased neurogenesis. This study examined dose-related effects of 21-day RSV treatment on markers associated with neurogenesis (DCX, PSA-NCAM) and angiogenesis (CD31) in the hippocampus at short (7-day) and long-term (85-day) intervals following global ischemia. In parallel, post-ischemic and stress-induced CORT levels and spatial memory in the Morris water maze were determined. METHODS: Five groups of male Wistar rats were included: sham/saline, ischemia/saline, ischemia/1 mg/kg RSV, ischemia/10 mg/kg RSV, and sham/10 mg/kg RSV. Changes in expression of plasticity markers were paralleled by assessment of basal- and stress-induced CORT secretions, and spatial memory performance. RESULTS: Our findings revealed a significant attenuation of ischemia-induced DCX/PSA-NCAM expression in RSV-treated rats, whereas RSV treatment increased angiogenesis in the injured CA1 region. RSV attenuated CORT levels 3 days post-ischemia and a trend toward attenuating CORT secretion in response to 15 minutes restraint stress. Increased swimming latencies in the target quadrant during the MWM probe trial in RSV-treated ischemic rats support beneficial effects of RSV on spatial memory retention. DISCUSSION: Our findings uncover time- and dose-related effects of RSV and global ischemia on the regulation of hippocampal plasticity. Changes in neuro- and angiogenesis are consistent with RSV neuroprotective effects, but appear independent of RSV regulatory effects on corticosterone secretion.

Effects of intranasal and peripheral oxytocin or gastrin-releasing peptide administration on social interaction and corticosterone levels in rats.

The intranasal route of drug administration has gained increased popularity as it is thought to allow large molecules, such as peptide hormones, more direct access to the brain, while limiting systemic exposure. Several studies have investigated the effects of intranasal oxytocin administration in humans as this peptide is associated with prosocial behavior. There are, however, few preclinical studies investigating the effects of intranasal oxytocin administration in rodents. Oxytocin modulates hypothalamic-pituitary-adrenal (HPA) axis functioning and it has been suggested that oxytocin's ability to increase sociability may occur through a reduction in stress reactivity. Another peptide that appears to influence both social behavior and HPA axis activity is gastrin-releasing peptide (GRP), but it is not known if these GRP-induced effects are related. With this in mind, in the present study, we assessed the effects of intranasal and intraperitoneal oxytocin and GRP administration on social interaction and release of corticosterone in rats. Intranasal and intraperitoneal administration of 20, but not 5 µg, of oxytocin significantly increased social interaction, whereas intranasal and peripheral administration of GRP (20 but not 5 µg) significantly decreased levels of social interaction. In addition, while intranasal oxytocin (20 µg) had no effect on blood corticosterone levels, a marked increase in blood corticosterone levels was observed following intraperitoneal oxytocin administration. With GRP, intranasal (20 µg) but not peripheral administration increased corticosterone levels. These findings provide further evidence that intranasal peptide delivery can induce behavioral alterations in rodents which is consistent with findings from human studies. In addition, the peptide-induced changes in social interaction were not linked to fluctuations in corticosterone levels.

Ethnopharmacology of Souroubea sympetala and Souroubea gilgii (Marcgraviaceae) and identification of betulinic acid as an anxiolytic principle.

The neotropical lianas Souroubea gilgii and Souroubea sympetala (Marcgraviaceae) were chosen for study as part of a phytochemical discovery strategy focusing on rare plant families in Central America. In participatory research, Q'eqchi' healers in Belize reported the use of these plants to reverse psychological symptoms inflicted by witchcraft. Extracts of two Souroubea species showed significant anti-anxiety activity in the elevated plus maze, a standardized test paradigm. Bioassay guided isolation led to the active principle, the pentacyclic triterpene, betulinic acid, which had activity in the elevated plus maze at 0.5mg/kg. Other phytochemicals isolated included α- and ß-amyrin, 2-hydroxyursolic acid, taraxenyl trans-4-hydroxy-cinnamate, naringenin, methyl ursolate, eriodytiol, methyl 2-α-hydroxyursolate, methyl 2-α-hydroxymaslinate, methyl betulinate, and condrilla sterol.

Academy of Nutrition and Dietetics and National Kidney Foundation: revised 2014 standards of practice and standards of professional performance for registered dietitian nutritionists (competent, proficient, and expert) in nephrology nutrition.

Compelling evidence indicates that the incidence of chronic kidney disease (CKD) is increasing because of an aging population and a higher prevalence of cardiovascular disease, diabetes, and hypertension. Nutrition management of patients with CKD requires early disease recognition, appropriate interpretation of the markers and stages of CKD, and collaboration with other health care practitioners. Better management of CKD can slow its progression, prevent metabolic complications, and reduce cardiovascular related outcomes. Caring for patients with CKD necessitates specialized knowledge and skills to meet the challenges associated with this growing epidemic. The Academy of Nutrition and Dietetics Renal Dietitians Practice Group and the National Kidney Foundation Council on Renal Nutrition, with guidance from the Academy of Nutrition and Dietetics Quality Management Committee, have updated the 2009 Standards of Practice in Nutrition Care and Standards of Professional Performance as a tool for registered dietitian nutritionists working in nephrology nutrition to assess their current skill levels and to identify areas for additional professional development in this practice area. The Standards of Practice apply to the care of patients/clients with kidney disease. The Standards of Professional Performance consist of six domains of professionalism, including: Quality in Practice, Competence and Accountability, Provision of Services, Application of Research, Communication and Application of Knowledge, and Utilization and Management of Resources. Within each standard, specific indicators provide measurable action statements that illustrate how nephrology nutrition principles can be applied to practice. The indicators describe three skill levels (ie, competent, proficient, and expert) for registered dietitian nutritionists working in nephrology nutrition.

Academy of Nutrition and Dietetics and National Kidney Foundation: revised 2014 Standards of Practice and Standards of Professional Performance for registered dietitian nutritionists (competent, proficient, and expert) in nephrology nutrition.

Compelling evidence indicates that the incidence of chronic kidney disease (CKD) is increasing because of an aging population and a higher prevalence of cardiovascular disease, diabetes, and hypertension. Nutrition management of patients with CKD requires early disease recognition, appropriate interpretation of the markers and stages of CKD, and collaboration with other health care practitioners. Better management of CKD can slow its progression, prevent metabolic complications, and reduce cardiovascular related outcomes. Caring for patients with CKD necessitates specialized knowledge and skills to meet the challenges associated with this growing epidemic. The Academy of Nutrition and Dietetics Renal Dietitians Practice Group and the National Kidney Foundation Council on Renal Nutrition, with guidance from the Academy of Nutrition and Dietetics Quality Management Committee, have updated the 2009 Standards of Practice in Nutrition Care and Standards of Professional Performance as a tool for registered dietitian nutritionists working in nephrology nutrition to assess their current skill levels and to identify areas for additional professional development in this practice area. The Standards of Practice apply to the care of patients/clients with kidney disease. The Standards of Professional Performance consist of six domains of professionalism, including: Quality in Practice, Competence and Accountability, Provision of Services, Application of Research, Communication and Application of Knowledge, and Utilization and Management of Resources. Within each standard, specific indicators provide measurable action statements that illustrate how nephrology nutrition principles can be applied to practice. The indicators describe three skill levels (ie, competent, proficient, and expert) for registered dietitian nutritionists working in nephrology nutrition.

Protracted effects of juvenile stressor exposure are mitigated by access to palatable food.

Stressor experiences during the juvenile period may increase vulnerability to anxiety and depressive-like symptoms in adulthood. Stressors may also promote palatable feeding, possibly reflecting a form of self-medication. The current study investigated the short- and long-term consequences of a stressor applied during the juvenile period on anxiety- and depressive-like behavior measured by the elevated plus maze (EPM), social interaction and forced swim test (FST). Furthermore, the effects of stress on caloric intake, preference for a palatable food and indices of metabolic syndrome and obesity were assessed. Male Wistar rats exposed to 3 consecutive days of variable stressors on postnatal days (PD) 27-29, displayed elevated anxiety-like behaviors as adults, which could be attenuated by consumption of a palatable high-fat diet. However, consumption of a palatable food in response to a stressor appeared to contribute to increased adiposity.

Gastrin-releasing peptide receptor signaling in the integration of stress and memory.

Neuropeptides act as signaling molecules that regulate a range of aspects of brain function. Gastrin-releasing peptide (GRP) is a 27-amino acid mammalian neuropeptide, homolog of the amphibian peptide bombesin. GRP acts by binding to the GRP receptor (GRPR, also called BB2), a member of the G-protein coupled receptor (GPCR) superfamily. GRP produced by neurons in the central nervous system (CNS) plays a role in synaptic transmission by activating GRPRs located on postsynaptic membranes, influencing several aspects of brain function. Here we review the role of GRP/GRPR as a system mediating both stress responses and the formation and expression of memories for fearful events. GRPR signaling might integrate the processing of stress and fear with synaptic plasticity and memory, serving as an important component of the set of neurobiological systems underlying the enhancement of memory storage by aversive information.

Bombesin receptor regulation of emotional memory.

Mammalian bombesin-like peptides neuromedin B (NMB) and gastrin-releasing peptide (GRP) act by activating NMB receptors (NMBR, BBl) and GRP receptors (GRPR,BB2), respectively. These two bombesin receptors are members of the G-protein-coupled receptor (GPCR) superfamily.In the brain, NMBR and GRPR are highly expressed in the brain areas involved in memory processing and emotional responses, such as the hippocampus and the amygdaloid nuclei. An increasing number of pharmacological and genetic studies in rodents indicate that NMBRs and GRPRs in brain regions including the dorsal hippocampus,the nucleus tractus solitarius, the basolateral amygdala,and cortical areas, regulate memory formation and expression, particularly for memories related to emotionally arousing tasks. GRPR signaling interacts with multiple protein kinase pathways as well as with other neurotransmitter,hormone, and growth factor systems in influencing memory formation. Together with evidence from human studies, the findings from rodent experiments suggest that bombesin receptors may be therapeutic targets in brain disorders involving memory dysfunction and anxiety.

Issues of obesity in kidney transplantation.

The purpose of this literature review is to evaluate the scientific evidence regarding the relationship between obesity and outcome of renal transplant recipients. The impact of obesity on kidney transplant outcomes continues to be controversial. Obesity seems to influence delayed graft failure, graft survival, and patient survival. A body mass index of 35 kg/m(2) or more is significant for greater posttransplant complications, especially new-onset transplant diabetes mellitus, wound complications, and posttransplant weight gain. Several important advances in the general medical management of the patient, both before and after transplantation, have occurred over the last decade. The decrease in mortality may be related to better patient management, whereas the improvement in graft survival is most likely the result of more effective immunotherapy and better management of hypertension and hyperlipidemia, which overall lessens the risk of obesity among kidney transplant recipients.

Corticotropin-releasing hormone, arginine vasopressin, gastrin-releasing peptide, and neuromedin B alterations in stress-relevant brain regions of suicides and control subjects.

BACKGROUND: Postmortem levels of several stress- and depression-relevant neuropeptides were assessed in brain regions of depressed suicides relative to control subjects that had died of other causes. METHODS: Brains of suicides and those that died from other causes were collected soon after death (typically <6 hours). Immunoreactivity levels (ir) of corticotropin-releasing hormone (CRH-ir) and arginine vasopressin (AVP-ir), and the bombesin analogs, gastrin-releasing peptide (GRP-ir), and neuromedin B (NMB-ir), were assessed. RESULTS: Levels of CRH-ir among suicides were elevated in the locus coeruleus (LC), frontopolar, dorsolateral prefrontal (DMPFC) and ventromedial prefrontal cortices, but were reduced at the dorsovagal complex (DVC). The concentration of AVP-ir was elevated at the paraventricluar hypothalamic nucleus, LC, and DMPFC, and reduced at the DVC. Finally, GRP and NMB variations, which might influence anxiety states, were limited, although GRP-ir within the LC of suicides was higher than in control subjects, while NMB-ir was reduced at the DVC of suicides. CONCLUSIONS: The data show several neuropeptide changes in relation to suicide, although it is premature to ascribe these outcomes specifically to the suicide act versus depression. Likewise, it is uncertain whether the neuropeptide alterations were etiologically related to suicide/depression or secondary to the depressive state.

Integrating clinical nutrition practice guidelines in chronic kidney disease.

Chronic kidney disease (CKD) is a permanent, progressive loss of kidney function characterized by a decline in glomerular filtration rate (GFR). Early identification of CKD risk factors provides an opportunity to prevent or delay the progression of kidney disease and decrease morbidity and mortality. There is increasing evidence to suggest that the adverse outcomes of CKD can be delayed or prevented by early detection and treatment. Current literature suggests that a low-protein, low-phosphorus diet may retard the progression of kidney disease. Other modifiable risk factors affecting CKD include proteinuria, hypertension, hyperglycemia, dyslipidemia, bone disease, anemia, and obesity. This discussion will review the current clinical nutrition guidelines for managing adult patients with CKD.

Bioelectrical impedance vs air displacement plethysmography and dual-energy X-ray absorptiometry to determine body composition in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) have significant shifts in fluid homeostasis that may impair measurements of body composition using methods based upon determinations of body water. Estimates of body water are fundamental for bioelectrical impedance analysis (BIA), which measures electrical resistance to estimate total body water and body composition. METHODS: BIA was compared with 2 other techniques: (1) air displacement plethysmography (ADP), which relies on measurements of body density to estimate body fat and fat-free masses; and (2) dual-energy x-ray absorptiometry (DXA), which depends on the relative attenuation of an x-ray beam to produce images of body fat and bone mineral. In study 1, BIA and ADP were performed on 38 ESRD patients (21 men and 17 women; age 51.3 +/- 2.2 years; weight 79.8 +/- 2.9 kg; body mass index [BMI] 27.4 +/- 0.9 kg/m2). In study 2, BIA and DXA were performed on 47 patients (22 men and 25 women; age 52.7 +/- 2.3 years; weight 73.6 +/- 2.9 kg; BMI 25.9 +/- 1.0 kg/m2). RESULTS: The ranges of percent body fat using BIA in studies 1 and 2 were from 7% to 57% and from 6% to 52%, respectively. Percent body fat measurements were significantly (p < .0001) correlated for BIA vs ADP (r = .74) and for BIA vs DXA (r = .84). Mean body fat as determined by BIA and ADP in study 1 was 31.8 +/- 2.0% and 36.3 +/- 1.8%* and by BIA and DXA in study 2 was 29.6 +/- 1.5% and 31.8 +/- 1.8%*, respectively (*p < .05 vs BIA). All 3 methods had similar variability associated with their measurements (coefficients of variation approximately 5%). The average body fat measured by BIA was less than ADP or DXA, regardless of gender or race. Furthermore, the variation was not greater at lower or higher body fat values. CONCLUSIONS: Body fat measurements using ADP and DXA were correlated with those using BIA across a relatively wide range of body fat levels in adults with ESRD. However, BIA appeared to underestimate body fat and overestimate fat-free mass, possibly because of increased measurements of body water. Because ADP is convenient and does not use body water content in determination of body density and body composition, it has very good potential as a relatively new technique to estimate percent body fat in adults with ESRD.

Differential involvement of amygdaloid CRH system(s) in the salience and valence of the stimuli.

Anxiety is a heterogeneous term encompassing not only state or trait characteristics but also a wide range of pathologies such as generalized anxiety disorders, phobias, panic and obsessive-compulsive disorders, acute stress disorder, and posttraumatic stress disorder. Given that diverse forms of anxiety exist, numerous animal models have been developed, which are considered to be useful in identifying mechanisms underlying anxiety states. Examples of such animal models include paradigms that assess the behavioral response to neurogenic (or painful stimuli) or psychogenic stressors or to cues that had previously been associated with painful stimuli. The present report presents data regarding the impact of stressors on corticotropin-releasing hormone (CRH), and relates these to changes in anxiety-like states. Specifically, we demonstrate that (1) psychogenic stressors influence the in vivo release of CRH at the central nucleus of the amygdala (CeA); (2) although CRH changes within the CeA are exquisitely sensitive to stressors, they are also elicited by positive stimuli; and (3) while treatment with diazepam attenuates behavioral signs of anxiety, the CRH release associated with a stressor is unaffected by the treatment. The position is offered that although release of CRH within the CeA is increased under stressful conditions, it is not a necessary condition for the consequent behavioral expression of anxiety-like reactions, at least not in minimally threatening situations. We suggest that the CRH responses at the CeA may be involved in a preparatory capacity and, as such, may accompany a range of emotionally significant stimuli, be they appetitive or aversive.

Improvement in nutritional parameters after initiation of chronic hemodialysis.

BACKGROUND: Protein-calorie malnutrition is highly prevalent in patients with chronic renal failure and on chronic dialysis therapy. Longitudinal studies evaluating nutritional outcomes after the initiation of chronic dialysis therapy in incident dialysis patients are limited. METHODS: This prospective cohort study evaluated time-dependent changes in several well-defined markers of nutritional status before and after initiation of chronic hemodialysis therapy. Fifty incident hemodialysis (HD) patients (60% men, 38% white, 32% with insulin-dependent diabetes mellitus) were studied. Multiple nutritional markers, including biochemical parameters and analysis of body composition, were assessed before the initial outpatient CHD treatment and every 3 months thereafter for 12 months. RESULTS: At baseline, nutritional markers correlated well with each other. After the initiation of HD therapy, there were marked improvements in most nutritional parameters, including serum albumin, serum prealbumin, normalized protein catabolic rate, fat mass, reactance, and phase angle (P < 0.05 for all). Improvements in nutritional parameters were influenced by baseline nutritional status; ie, baseline nutritional parameters were predictors of their end-of-study value. CONCLUSION: Initiation of CHD therapy is associated with improvements in most nutritional markers. Nutritional benefits of increased solute clearance provided by the initiation of chronic dialysis therapy prevail over its potential catabolic effects. However, the extent of improvement was dependent on nutritional status at the time of initiation of dialysis therapy, which remained an important determinant of subsequent nutritional improvements during the first year of treatment.