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PubMed2004

The NMDA receptor antagonist MK-801 alters lipoprivic eating elicited by 2-mercaptoacetate.

Eating behavior is controlled, at least in part, by levels of circulating metabolic fuels such as glucose and free fatty acids, and drugs that interfere with the availability of these fuels can elicit eating. One such drug is 2-mercaptoacetate (2MA), an inhibitor of fatty acid oxidation. Evidence also suggests that NMDA receptors may mediate some aspects of normal eating and satiety. The present study was conducted in order to determine whether NMDA receptors may play a role in feeding elicited by 2MA. Rats received intraperitoneal injections of either saline, 2MA, the non-competitive NMDA receptor antagonist MK-801 or a combined injection of 2MA and MK-801, and subsequent intake of a fat-enriched, mash diet was measured at 1, 2, 3 and 4 h post-injection. Results showed that cumulative food intake was significantly increased by 2MA alone, as compared to saline controls, with most of the 2MA-elicited eating occurring during the first hour post-injection. While MK-801 alone did not alter food intake, it did have a biphasic effect on feeding elicited by 2MA. MK-801 initially suppressed and later enhanced eating elicited by 2MA. Although it is unclear whether MK-801 is acting centrally, peripherally or both to alter 2MA-induced eating, these results implicate NMDA receptors and the neurotransmitter glutamate in the regulation of lipid-associated eating and satiety.

Animals↗
PubMed2005

Prospective isolation of late development multipotent precursors whose migration is promoted by EGFR.

A simple procedure to isolate neural stem cells would greatly facilitate direct studies of their properties. Here, we exploited the increase in EGF receptor (EGFR) levels, that occurs in late development stem cells or in younger precursors upon exposure to FGF-2, to isolate cells expressing high levels of EGFR (EGFR(high)) from the developing and the adult brain. Independently of age and region of isolation, EGFR(high) cells were highly enriched in multipotent precursors and displayed similar antigenic characteristics, with the exception of GFAP and Lex/SSEA-1 that were mainly expressed in adult EGFR(high) cells. EGFR levels did not correlate with neurogenic potential, indicating that the increase in EGFR expression does not directly affect differentiation. Instead, in the brain, many EGFR(high) precursors showed tangential orientation and, whether isolated from the cortex or striatum, EGFR(high) precursors displayed characteristics of cells originating from the ventral GZ such as expression Dlx and Mash-1 and the ability to generate GABAergic neurons and oligodendrocytes. Moreover, migration of EGFR(high) cells on telencephalic slices required EGFR activity. Thus, the developmentally regulated increase in EGFR levels may affect tangential migration of multipotent precursors. In addition, it can be used as a marker to effectively isolate telencephalic multipotent precursors from embryonic and adult tissue.

Animals↗
PubMed2002

Feeding dysfunction is associated with poor growth and health status in children with cerebral palsy.

OBJECTIVE: To describe parent-reported feeding dysfunction and its association with health and nutritional status in children with cerebral palsy. DESIGN: Anthropometry was measured and z scores calculated. The Child Health Questionnaire was used to assess health status, and a categorical scale (none to severe) was used to classify subjects according to severity of feeding dysfunction. SUBJECTS: 230 children (9.7+/-4.6 years; 59% boys) with moderate to severe cerebral palsy were recruited from 6 centers in the United States and Canada. STATISTICAL ANALYSES: Descriptive statistics, the Kruskal-Wallis and Pearson chi2 tests. RESULTS: Severity of feeding dysfunction was strongly associated with indicators of poor health and nutritional status. The mean weight z scores were -1.7, -2.5, -3.3, and -1.8 among children with none, mild, moderate, or severe (largely tube-fed) feeding dysfunction, respectively (P= .003). Similar results were observed for height z score (P=.008), triceps z score (P=.03), and poor Global Health score (part of the Child Health Questionnaire) (P<.001). Subjects who were tube fed were taller (P=.014) and had greater body fat stores (triceps z score, P=.001) than orally fed subjects with similar motor impairment. For subjects exclusively fed by mouth, a dose-response relationship was observed between feeding dysfunction severity and poor nutritional status. Subjects with only mild feeding dysfunction had reduced triceps z score (-0.9) compared with those with no feeding problems (-0.3). CONCLUSION: For children with moderate to severe cerebral palsy, feeding dysfunction is a common problem associated with poor health and nutritional status. Even children with only mild feeding dysfunction, requiring chopped or mashed foods, may be at risk for poor nutritional status. Parental report of feeding dysfunction with a structured questionnaire may be useful in screening children for nutritional risk.

Adolescent↗
PubMed2003

Chewing behaviour and bolus formation during mastication of meat with different textures.

During chewing, meat is mashed under compression and shear bite forces whilst saliva is incorporated. The resulting mixture is shaped into a cohesive bolus by agglomeration of small particles, and triggers a swallow. This study aimed to investigate the relationship between chewing behaviour and bolus formation of meat with different textures. Twenty-five consenting young adults participated in this study. Electromyographic activity was recorded from surface electrodes on the elevator muscles (masseter and temporalis) during mastication of cold beef. Two different textures (T(1): tough and dry; T(2): tender and juicy) were studied, and subjects were asked to chew the beef and then spit out the bolus either: (1) after a constant chewing period of 7s or (2) when the bolus was ready to be swallowed. Meat samples were weighed before and after chewing to determine weight changes due to saliva incorporation and the release of meat juice. Cutting tests were applied to measure the maximum shear force. The mechanical shear force was maximal for meat before chewing (T(1)=124 N/cm(2); T(2)=83 N/cm(2)) and decreased with increased chewing duration. Texture differences analysed from mechanical measurements remained significant even when the boli were ready for swallowing (T(1)=39 N/cm(2); T(2)=32 N/cm(2)); the toughest meat gave the toughest bolus. Muscular activity adapted to the texture of the meat as soon as chewing began, and remained constant over the observed chewing period. Mean muscular activity was higher during the chewing of tough meat than during the chewing of tender meat. As a consequence, by the time a bolus was ready to be swallowed, more saliva had been incorporated into the tough meat samples (mean weight increase: 36%) than the tender meat samples (mean weight increase: 30%).

Adult↗
PubMed2002

Wnt-1 promotes neuronal differentiation and inhibits gliogenesis in P19 cells.

Wnt-1, the vertebrate counterpart of the Drosophila wingless gene, plays an important role in the early morphogenesis of neural tissues. In this report, we have shown that overexpression of Wnt-1 can direct embryonic carcinoma P19 cells to differentiate into neuron-like cells in the absence of retinoic acid. Immunocytochemistry showed that these cells expressed neuronal markers, such as the neurofilament (NF) and microtubule-associated protein 2 (MAP2), but failed to express the glial cell marker, glial fibrillary acidic protein (GFAP). RT-PCR revealed that two basic helix-loop-helix (bHLH) genes, Mash-1 and Ngn-1, were up-regulated during the differentiation stage of Wnt-1-overexpressing P19 cells. These results suggest that the Wnt-1 gene promotes neuronal differentiation and inhibits gliogenesis during the neural differentiation of P19 cells, and that neural bHLH genes might be involved in this process.

Animals↗
PubMed2000

The hedonic impact and intake of food are increased by midazolam microinjection in the parabrachial nucleus.

Benzodiazepines have been reported to induce eating when administered into the brainstem of rats (either the fourth ventricle or the parabrachial nucleus). Benzodiazepines in the brainstem also have been reported to enhance the hedonic impact of taste, as measured by hedonic/aversive taste reactivity patterns, when administered to the fourth ventricle. The present study examined whether the parabrachial nucleus in particular is a brainstem site of the benzodiazepine-produced enhancement of eating and palatability. Food intake (cereal mash) was measured after brainstem microinjections of midazolam or vehicle (0.0, 7.5, and 15.0 microg) into the parabrachial nucleus, the nucleus of the solitary tract, the pedunculopontine tegmental nucleus, or the fourth ventricle (60 microg). We used the taste reactivity paradigm to measure hedonic/aversive affective reactions elicited from rats by oral infusions of a bittersweet solution (7% sucrose-0.01% quinine). Positive hedonic reactions and negative aversive reactions to sucrose-quinine were also measured after microinjections of midazolam (0.0, 7.5, and 15 microg) into the parabrachial nucleus. Midazolam increased food intake and selectively enhanced positive hedonic taste reactivity patterns to the bittersweet solution when microinjections were delivered to the parabrachial nucleus. When administered to the other brainstem sites at the same doses, however, midazolam had no effect. We therefore conclude that the parabrachial nucleus can mediate the benzodiazepine-induced enhancement of the hedonic impact of taste as well as mediating the enhancement of eating behavior.

Animals↗
PubMed2003

Role of Phox2b and Mash1 in the generation of the vestibular efferent nucleus.

The inner ear (vestibular and cochlear) efferent neurons are a group of atypical motor-like hindbrain neurons which innervate inner ear hair cells and their sensory afferents. They are born in the fourth rhombomere, in close association with facial branchial motor neurons, from which they subsequently part through a specific migration route. Here, we demonstrate that the inner ear efferents depend on Phox2b for their differentiation, behaving in that respect like hindbrain visceral and branchial motor neurons. We also show that the vestibular efferent nucleus is no longer present at its usual site in mice inactivated for the bHLH transcription factor Mash 1. The concomitant appearance of an ectopic branchial-like nucleus at the location where both inner ear efferents and facial branchial motor neurons are born suggests that Mash1 is required for the migration of a subpopulation of rhombomere 4-derived efferents.

Animals↗
PubMed2004

Sox6 overexpression causes cellular aggregation and the neuronal differentiation of P19 embryonic carcinoma cells in the absence of retinoic acid.

The Sox6 gene is a member of the Sox gene family that encodes transcription factors. Previous studies have suggested that Sox6 plays an important role in the development of the central nervous system. Aggregation of embryonic carcinoma P19 cells with retinoic acid (RA) results in the development of neurons, glia and fibroblast-like cells. In this report, we have shown that Sox6 mRNA increased rapidly in P19 cells during RA induction and then decreased during the differentiation of P19 into neuronal cells. To explore the possible roles of Sox6 during this process, stably Sox6-overexpressing P19 cell lines (P19[Sox6]) were established. These P19[Sox6] had acquired both characteristics of the wild-type P19 induced by RA. First, P19[Sox6] cells showed a marked cellular aggregation in the absence of RA. Second, P19[Sox6] could differentiate into microtubule-associated protein 2 (MAP2)-expressing neuronal cells in the absence of RA. Sox6 expression could cause the activation of endogenous genes including the neuronal transcription factor Mash-1, the neuronal development-related gene Wnt-1, the neuron-specific cell adhesion molecule N-cadherin, and the neuron-specific protein MAP2, resulting in neurogenesis. Moreover, E-cadherin, a major cell adhesion molecule of wild-type P19, was strongly induced by Sox6, resulting in cellular aggregation without RA. Thus Sox6 may play a critical role in cellular aggregation and neuronal differentiation of P19 cells.

Animals↗
PubMed1979

Distribution of intimal smooth muscle cell masses and their relationship to early atherosclerosis in the abdominal aortas of young swine.

In the abdominal aortas of young mash-fed swine, intimal cell masses (pads, cushions) are located predominantly away from blood vessel orifices. They are found scattered throughout the aorta but nevertheless have a definite pattern of distribution. In the distal one half of the abdominal aorta, they are more frequent in the ventral quandrant than in the dorsal or either lateral quadrant. In the proximal half, intimal cell masses are more frequent in the dorsal quadrant. When experimental atherosclerosis is induced in the abdominal aortas of young swine by either a hypercholesterolemic diet or by aortic ballooning followed by a hypercholesterolemic diet, the distribution of early lesions is similar. The lesions are found predominantly in quadrants where intimal cell masses were found to be most frequent in the control group of swine. The results suggest that most of the lesions, though not necessarily all, arose from pre-existing intimal cell masses beneath the aortic surface.

Animals↗
PubMed2003

Effects of systematic variation in presatiation and fasting on the behavioural satiety sequence in male rats.

Preclinical research on the neurobiology of appetite regulation is increasingly employing detailed behavioural assessment in addition to measures of food intake. One of the most widely used approaches examines treatment effects on the behavioural satiety sequence (BSS), a concept describing the predictable pattern of behavioural change (feeding-->grooming-->resting) associated with the process of satiation in rats, mice and other mammals. Surprisingly, however, comparatively little published detail is available concerning the impact of more natural appetite modulators on the BSS. In two separate experiments, a continuous monitoring technique was used to calibrate the effects of prefeeding (3, 6 and 9 min) and prior fasting (3, 6 and 12 h) on the microstructure of rat behaviour during a 1 h test with palatable mash. Prefeeding significantly increased eating latencies and reduced both food intake and total duration (but not frequency) of feeding behaviour. The reduction in time spent eating was most evident during the first 15 min of the test when feeding is normally at peak levels. Although behavioural structure was fully preserved in all test conditions, the two larger preloads resulted in shifts to the left (i.e., an acceleration) in the BSS. In contrast, fasting for 6 and 12 h (but not 3 h) increased food intake and duration (but not frequency) of feeding behaviour in the early part of the test. All fasting conditions (including 3 h) produced considerable shifts to the right (i.e., a delay) in the BSS, confirming the greater sensitivity of this measure relative to food intake per se. The potential utility of these reference profiles is discussed in relation to drug-induced changes in food intake and the BSS.

Animals↗
PubMed2003

Palatability, food intake and the behavioural satiety sequence in male rats.

Food intake is influenced not only by nutritional status but also by diverse environmental factors. Indeed, a unique quality of food reward is its strong modulation by palatability cues, such as taste, with animals generally preferring diets that are sweet and avoiding those that are either bitter or sour. As appetite suppressants (including those currently in development) could alter food intake by modifying taste sensitivity and/or palatability, the aim of the present study was to characterise the influence of taste adulteration on the normal structure of feeding behaviour, i.e., the behavioural satiety sequence (BSS). Adult male rats were initially habituated both to the basic test diet (mash) and the test arena. Following stabilisation of basal intake, a continuous monitoring technique was used to profile behaviour in weekly 1-h sessions during which the animals were presented, in counterbalanced order, with the basic diet (control) or one of four taste-adulterated variants (0.015% quinine, 0.04% quinine, 0.2% saccharin, 0.3% saccharin). Food intake was strongly suppressed by the higher quinine concentration but was not significantly altered by any of the other additives. Behavioural analysis revealed that this anorectic-like response to 0.04% quinine-adulterated food was associated with a significant reduction in the peak feeding response, highly atypical intermittent food sampling/digging and the virtual absence of resting behaviour. Importantly, this pattern of behavioural change is readily distinguishable from those seen in response to other manipulations that reduce intake, including selective anorectics, sedatives and psychostimulants. Despite the lack of significant effect on food intake or the duration of feeding behaviour, dietary adulteration with 0.015% quinine (and, to a lesser degree, 0.3% saccharin) produced some effects on behavioural structure/time course consistent with a mild aversive response, i.e., bouts of midsession food sampling and a delay in the transition from eating to resting. Data are discussed in relation to the specific behavioural signature to quinine-induced anorexia and its potential utility in identifying appetite suppressants that may modify intake via changes in taste sensitivity and/or palatability.

Animals↗
PubMed1998

Hyperphagia in pre-fed rats following oral delta9-THC.

Using a pre-feed paradigm, the effects of orally-administered delta9-tetrahydrocannabinol (THC) on low baseline levels of nocturnal feeding were assessed. Following 2-h access to a palatable wet mash diet at dark onset, adult male Lister hooded rats (Charles River) were treated with either sesame seed oil vehicle or delta9- tetrahydrocannabinol (0.063, 0.12, 0.25, 0.5, 1.0, or 2.0 mg/kg). One hour later, rats were allowed ad libitum access to standard chow, and intakes were monitored over the subsequent 24 h. Doses of 0.5, 1.0, and 2.0 mg/kg produced substantial hyperphagia during the first hour of testing. Subsequently, rats compensated for their overconsumption so that 24-h intakes were similar in all conditions. The data confirm anecdotal reports of the orexigenic actions of exogenous cannabinoids and suggest a critical role for endogenous cannabinoid systems in the regulation of appetite.

Administration, Oral↗
PubMed1998

Antineophobic effect of the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one in male rats.

The neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one (pregnanolone) and benzodiazepine receptor (BZR) agonists share sedative, anxiolytic, and anticonvulsant properties. Recent evidence suggests that like BZR agonists, pregnanolone may also modulate feeding responses. The present experiments examined the behavioral mechanisms responsible for any hyperphagic effect of pregnanolone. The effect of pregnanolone (1-10 mg/kg i.p.) on the intake and microstructure of licking for two sucrose solutions (1 and 3%) in well familiarized nondeprived male rats under either light or dark conditions was examined. Pregnanolone had no effect on either intake or the duration or number of bouts of licking in these experiments, although in all cases the intrabout lick rate was significantly reduced at the highest dose. Pregnanolone (1-10 mg/kg) also failed to increase intake of a sweet wet mash in familiarized nondeprived male rats. However, in a food choice test where both novel and familiar food items were available, pregnanolone (1-3 mg/kg) significantly increased the time spent eating the novel food. These results suggest that unlike BZR agonists, which enhance feeding responses directly, pregnanolone may facilitate feeding secondarily via an attenuation of anxiety.

Animals↗
PubMed2000

Seasonal variation of Zn, Pb, Cu and Cd concentrations in the root-sediment system of Spartina maritima and Halimione portulacoides from Tagus estuary salt marshes.

Concentrations of Zn, Pb, Cu and Cd have been determined in leaves, stems and roots of Spartina maritima and Halimione portulacoides from the Tagus estuary salt mash (Corroios) and in the sediments between their roots. Biological materials and sediments were sampled every 2 months, between July 1991 and July 1992. Root biomass increased from July to September and from January to March. The greatest metal concentrations occurred in the roots, with lowest levels in January and increasing levels during the growth periods. Zn, Pb and Cu in sediments exhibited a corresponding change in concentrations, reaching maximum in January and subsequently decreasing in spring. The ratios between metal concentrations in the root and in sediments were higher for H. portulacoides when compared to S. maritima, whose roots are surrounded by a more acidic and reduced sediment environment. It was concluded, therefore, that H. portulacoides is a more effective accumulator of metals than S. maritima, and both root-sediment systems exhibited a seasonal variation of metal concentrations.

Cadmium↗
PubMed2000

Expression of neural properties in olfactory cytokeratin-positive basal cell line.

A cytokeratin (CK)(+), horizontal basal cell (HBC)-like cell line from murine olfactory epithelium, DBC1.2, was characterized. Histochemically, it is CK14(+), CK18(-), neuron-specific tubulin (NST)(+) and capable of binding Bandeiraea simplicifolia lectin I. RT-PCR studies revealed that it expresses mRNAs for EGF receptor, NST, Pax-6, but not for Mash-1 and neurogenin-1. Retinoic acid reduced the expression of CK14 and CKs recognized by polyclonal anti-keratin antibody, whereas it induced nestin. These results suggest that DBC1.2 shares the properties of HBCs and neural cells.

Animals↗
PubMed2003

Implication of Trip15/CSN2 in early stage of neuronal differentiation of P19 embryonal carcinoma cells.

Trip15/CSN2 is a transcriptional corepressor/a component of COP9 signalosome (CSN) and participates in various signaling pathways. However, participation of Trip15/CSN2 in neural differentiation is still obscure. Here, we show that Trip15/CSN2 plays a critical role in neuronal differentiation. The expression of Trip15/CSN2 mRNA was induced at an early stage of neuronal differentiation in the retinoic acid (RA)-treated P19 cells, but not in the triiodothyronine (T3)-primed cardiac muscular cell differentiation. The expression of Trip15/CSN2 mRNA in the rat brain was detected at E14 and the protein was localized in the nuclei of neonatal rat CNS neurons. Enforced expression of sense rat Trip15/CSN2 mRNA caused the downregulation of Oct-3/4 mRNA expression and was sufficient to convert P19 cells into neurons, but not glial cells, only after the aggregation without RA. In the presence of RA, exogenous expression of the sense mRNA caused the intense and rapid induction of neurogenic Brn-2 and Mash-1 mRNA expressions accompanying the strong downregulation of Oct-3/4 mRNA expression, and stimulated both neuronal and glial cell differentiations of P19 cells. In contrast, enforced expression of the antisense mRNA suppressed the commitment of RA-treated aggregation form of P19 cells to neuronal lineage. These data strongly suggest that Trip15/CSN2 could implicate in the commitment of multipotent embryonal carcinoma (EC) cells to neuronal fate through the downregulation of Oct-3/4 which suppresses neurogenic genes. Moreover, in addition to Trip15/CSN2, RA-regulated other factor(s) may be required for glial cell differentiation.

Animals↗
PubMed2000

Dose-response effects of orexin-A on food intake and the behavioural satiety sequence in rats.

Although intracerebroventricular (i.c.v.) administration of orexin-A has been reported to stimulate food intake and/or feeding behaviour in rats, mice and goldfish, little attention has thus far been paid to its effects on normal patterns of feeding. In the present study, a continuous monitoring technique was used to characterise the effects of this novel neuropeptide on the microstructure of rat behaviour during a 1-h test with palatable wet mash. Particular attention was devoted to the behavioural satiety sequence, in which feeding is followed by grooming and resting. Although results confirmed the hyperphagic effects of orexin-A (3.33-30.0 microg i.c. v.), gross behavioural analysis failed to reveal any reliable effects of peptide treatment on eating, drinking, sniffing, grooming, resting, locomotion or rearing. However, microstructural analysis revealed behavioural effects of orexin-A that are both dose- and time-dependent. At lower doses (3.33-10.0 microg), orexin-A primarily delayed behavioural satiety, i.e. the normal transition from eating to resting. In contrast, the 30 microg dose initially induced a sedative-like effect, significantly suppressing eating and other active behaviours for the first 15-20 min of the test period. This sedative-like effect resulted in a phase-shifting of the entire behavioural sequence with higher than control levels of eating, grooming, locomotion, rearing and sniffing observed over the second half of the test session. Present findings illustrate the advantages of microstructural behavioural analysis and suggest that the hyperphagic response to low doses of orexin-A results largely from a delay in behavioural satiety while that seen in response to high doses may occur in rebound to initial behavioural suppression. Further studies will be required to confirm the identity of the specific orexin receptors (i.e. OX(1) or OX(2)) involved in mediating the dose-dependent behavioural effects reported.

Animals↗
PubMed1999

A review of traditional fermented foods and beverages of Zimbabwe.

Several traditional fermented foods and beverages are produced at household level in Zimbabwe. These include fermented maize porridges (mutwiwa and ilambazi lokubilisa) fermented milk products (mukaka wakakoralamasi and hodzeko) non-alcoholic cereal-based beverages (mahewu, tobwa and mangisi) alcoholic beverages from sorghum or millet malt (doroluthwala and chikokivana) distilled spirits (kachasu) and fermented fruit mashes (makumbi). There are many regional variations to the preparation of each fermented product. Research into the processing technologies of these foods is still in its infancy. It is, therefore, important that the microbiology and biochemistry of these products, as well as their technologies be studied and documented in order to preserve them for future generations. This article reviews the available information regarding traditional fermented foods in Zimbabwe and makes recommendations for potential research areas.

Animals↗