Biomedical subjects

M J Guerra

Publications and source records attributed to M J Guerra.

32 records · Page 2Linked to original sources

PubMed1997

Treadmill running induces striatal Fos expression via NMDA glutamate and dopamine receptors.

Several non-physiological stimuli (i.e. pharmacological or electrical stimuli) have been shown to induce Fos expression in striatal neurons. In this work, striatal Fos (i.e. Fos-like) expression was studied after physiological stimulation, i.e. motor activity (treadmill running at 36 m/min for 20 min). In rats killed 2 h after the treadmill session, Fos expression was observed in the medial region of the rostral and central striatum, and in the dorsal region of the caudal striatum. Fos expression was prevented by pretreatment with the non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 (0.1 mg/kg) or the D1 dopamine receptor antagonist SCH-23390 (0.1 mg/kg), but not by pretreatment with the D2 receptor antagonist eticlopride (0.5 mg/kg). Thirty-six hours after 6-hydroxydopamine lesion, a considerable reduction in treadmill-induced Fos expression was observed in both sides; however, Fos expression in the lesioned striatum was higher than in the contralateral intact striatum. Several weeks after unilateral 6-hydroxydopamine lesion of the nigrostriatal system, treadmill-induced Fos expression was significantly, but not totally, reduced in the lesioned striatum. Corticostriatal deafferentation also led to considerable reduction in treadmill-induced Fos expression. The present results indicate that exercise induces striatal Fos expression and that, under physiological stimulation, concurrent activation of D1 and NMDA receptors is necessary for such expression to occur. Reduction of Fos expression is practically absolute after acute blockage of these receptors, but not after lesions, possibly due partially to compensatory changes.

Afferent Pathways↗

PubMed1997

Time course of striatal, pallidal and thalamic alpha 1, alpha 2 and beta 2/3 GABAA receptor subunit changes induced by unilateral 6-OHDA lesion of the nigrostriatal pathway.

Immunocytochemical techniques were used to investigate the distribution and abundance of GABAA receptor subunits (alpha 1, alpha 2 and beta 2/3) in the brains of unilaterally 6-OHDA-lesioned rats. Three and 7 days after lesion, the alpha 2-subunit was significantly more abundant in the lesion-ipsilateral striatum than in the lesion-contralateral striatum; by 4 weeks after lesion, however, no significant between-side differences were observed. Three and 7 days after lesion, the alpha 1-subunit was significantly less abundant in the lesion-ipsilateral globus pallidus than in the lesion-contralateral side; again, this difference disappeared within 4 weeks of lesion. Similarly, alpha 1 was initially less abundant in several relay thalamic nuclei on the lesioned side while alpha 2 was initially more abundant in intralaminar thalamic nuclei on the lesioned side. There were no significant between-side changes for the beta 2/3-subunits. Comparison of non-lesioned and 6-OHDA-lesioned rats revealed significant differences in brain areas which also showed differences on comparison of the lesioned and non-lesioned sides of 6-OHDA-lesioned rats. These results suggest that there is an early adaptation to the lesion, achieved through changes in GABAA receptor abundance. That some of these changes are no longer apparent after 4 weeks is due not only to partial reversion of the changes in the lesioned side but also to compensatory changes in the non-lesioned side.

Animals↗

PubMed1996

Previous dopaminergic innervation is not necessary for the development of dopamine supersensitivity in rat striatal neurons.

The development of supersensitivity to dopamine by striatal neurons is widely considered to be a response to interruption of dopaminergic synaptic function. However, it is not clear whether pre-existing dopaminergic innervation is in fact necessary for supersensitivity to develop. In this study, rat foetal striatal cells were obtained prior to their innervation by dopaminergic fibres, and grafted into the cortex or thalamus of adult rats. In the absence of dopaminergic innervation, the grafts developed and became organized into striatum-like and non-striatum-like patches. Both in animals with intrathalamic and in animals with intracortical grafts, systemic administration of a low dose of apomorphine (0.25 mg/kg) induced intense fos expression in striatum-like patches not innervated by dopaminergic fibres. These results indicate that pre-existing dopaminergic innervation is not required for the development of supersensitivity, and that dopaminergic innervation is necessary to develop an adequate synergistic interaction between D1 and D2 receptors.

Animals↗

PubMed1996

Intrathalamic implants of GABA-releasing polymer matrices reduce motor impairments in rats with excitotoxically lesioned striata.

Current models of basal ganglia disorders suggest that the choreoathetosis is the end result of reduced GABAergic inhibition of the motor thalamus. GABA-releasing polymer matrices or control matrices without GABA were implanted either unilaterally or bilaterally in the vicinity of the ventromedial thalamic nucleus of normal rats and of rats with unilateral or bilateral excitotoxic striatal lesions (rat model of Huntington's disease), to study the effects of these GABA-releasing matrices on amphetamine-induced rotational behavior (unilateral implants in unilaterally lesioned rats) and on overnight spontaneous locomotor activity (bilateral implants in bilaterally lesioned rats). Unilateral implants led to a reduction (about 25%) in motor asymmetry; the response was transitory, probably because of the exhaustion of GABA release by the matrix. Some rats showed a more marked and permanent reduction of motor asymmetry, but this was probably due to lesion of the ventromedial nucleus or its thalamocortical projection. Bilateral implants of GABA-releasing matrices (but not control matrices) led to a marked (about 65%) but again transitory reduction in the locomotor hyperactivity induced by bilateral striatal lesion. These results suggest that implantation of a GABA-releasing source may be an effective alternative to intrathalamic fetal-tissue grafts or lesions as an experimental approach to the treatment of hyperkinetic movement disorders.

Animals↗

PubMed1996

Time course of striatal changes induced by 6-hydroxydopamine lesion of the nigrostriatal pathway, as studied by combined evaluation of rotational behaviour and striatal Fos expression.

Changes taking place after unilateral 6-hydroxydopamine lesion of the dopaminergic nigrostriatal system have been studied by performing spontaneous, amphetamine-induced and apomorphine-induced rotational behaviour testing and tyrosine hydroxylase (TH) and Fos protein immunohistochemistry in the same rats. Apomorphine at a low dosage (0.25 mg/kg) induced contraversive rotation and supersensitive striatal Fos expression that were detected 24-48 h post-lesion and gradually increased in magnitude. Twenty-four hours after lesion, both high (5 mg/kg) and low doses (0.5 mg/kg) of D-amphetamine induced contraversive rotation and intense striatal Fos activation on the denervated side; however, only the higher dose induced Fos on the normal side. Two, 3 and 4 days after lesion, 0.5 mg/kg amphetamine induced contraversive rotation, but 5 mg/kg induced transitory contraversive rotation which switched to ipsiversive. In the normal striatum, only high doses of amphetamine induced Fos, but Fos induction in the denervated striatum was similar with both doses: areas showing severely decreased TH immunoreactivity still showed considerable Fos immunoreactivity, and some areas still showing TH immunoreactivity had higher Fos density than in the normal side. Seven and 14 days after lesion the loss of TH immunoreactivity and apomorphine-induced supersensitive Fos expression were more evenly distributed, and amphetamine induced only ipsiversive rotation and a low density of Fos-positive nuclei in the denervated striatum. These results indicate that the severe and progressive loss of dopaminergic terminals is counteracted by an early and rapidly progressing dopamine supersensitivity, together with a higher susceptibility to drug-induced dopamine release. This explains the apparently paradoxical contraversive rotation induced by amphetamine during the first week post lesion. However, experiments involving successive drug injections indicated that only the first amphetamine injection releases dopamine from the lesioned terminals.

Amphetamine↗

PubMed1995

Cortical stimulation induces Fos expression in striatal neurons via NMDA glutamate and dopamine receptors.

Cortical electrical stimulation has been shown to induce dense and widespread Fos expression throughout the ipsilateral and contralateral striatum. This raises interest for studying the mechanisms underlying the regulation of striatal neuron activity by cortical afferents, and for elucidating the interactions with other systems. However, the receptors mediating cortical-stimulation-induced expression of Fos in striatal neurons have not been identified. This was studied in the work reported here by stimulating the cortex after administration of glutamate or dopamine receptor antagonists, or after 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal dopaminergic system. Pretreatment with the non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 led to a marked reduction in the stimulation-induced density of Fos-immunoreactive nuclei in both the medial (about 80% reduction) and lateral (about 50-60% reduction) striatum. Preadministration of the D1-selective dopamine antagonist SCH-23390 alone or in combination with the D2-selective dopamine antagonist eticlopride led to a reduction in the stimulation-induced density of Fos-positive nuclei of about 60-65% in the lateral striatum, but no significant change in the medial region. The effects of 6-OHDA lesion were less pronounced, and the stimulation-induced density of Fos-immunoreactive nuclei decreased by only about 25% in the lateral region. These results indicate that both dopamine and NMDA glutamate receptors are involved in the induction of Fos by cortical stimulation, and support the hypothesis that cortex-dopamine interactions in the lateral striatum may be functionally different from those in the medial striatum.

Animals↗

PubMed1995

Intrathalamic striatal grafts survive and affect circling behaviour in adult rats with excitotoxically lesioned striatum.

Current models of basal ganglia disorders suggest that choreoathetosis is the end result of reduced GABAergic inhibition of the motor thalamus. Graft-derived release of GABA from intrastriatal striatal grafts has also been reported. In the present work, cell suspension grafts from embryonic day 14-15 rat striatal primordia were implanted close to the ventromedial thalamic nucleus to investigate whether they can develop and survive in this ectopic location, and whether they induce changes in the circling behaviour of the host. The grafts were implanted either in normal rats or in rats whose striatum had been lesioned with ibotenic acid. These grafts were implanted either ipsilateral or contralateral to the lesioned striatum. Additionally, some rats received intrastriatal grafts, and lesioned but non-grafted rats and lesioned rats that had received injections of saline or of cell suspensions from fetal spinal cord in the thalamus were used as control. Four to eight months after transplantation, circling behaviour after amphetamine or apomorphine injection was evaluated. Serial sections were stained with Cresyl Violet and studied immunohistochemically with antibodies against DARPP-32 (dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein, as striatal marker), Fos protein, glutamate decarboxylase (67,000 mol. wt), glutamate decarboxylase (65,000 mol. wt) and GABA. Cresyl Violet sections showed that the intrathalamic striatal grafts developed into tissue masses resembling those observed in intrastriatal striatal grafts. DARPP-32 immunohistochemistry revealed that the grafts were composed of DARPP-32 immunoreactive (striatum-like) and DARPP-32-negative patches. The intrathalamic grafts of rats which had received a low dose of apomorphine (0.25 mg/kg) 2 h before perfusion showed clusters of intensely Fos-immunoreactive nuclei throughout the transplant, indicating that these cells had developed dopamine receptors and supersensitivity to dopamine agonists. Double Fos and DARPP-32 immunohistochemistry revealed that the Fos-positive nuclei were located in the striatum-like areas. Finally, the intrathalamic grafts also contained neurons immunoreactive to GABA and glutamate decarboxylase (65,000 and 67,000 mol. wt). Rats that had received intrathalamic grafts contralateral to the lesioned striatum (i.e. contralateral to the lesion-induced turning direction) showed a significant reduction of circling both after amphetamine (78% reduction) or apomorphine (77% reduction) injection. Rats that had received grafts ipsilateral to the lesioned striatum showed a 75% decrease in amphetamine-induced circling, but no significant change in apomorphine-induced circling. No significant drug-induced circling was observed in non-lesioned and grafted rats. Sham grafting (saline) or grafting of weakly GABAergic tissue (fetal spinal cord) had no significant effects on lesion-induced circling behaviour.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Cortical stimulation induces fos expression in intrastriatal striatal grafts.

Innervation of intrastriatal grafts of fetal striatal tissue by host corticostriatal projections has been shown in a number of previous studies in rats. In the work reported here, induction of Fos protein in grafted striatal neurons by electrical stimulation of the host frontoparietal cortex has been used as cell-level marker of corticostriatal postsynaptic responses within the striatal grafts. Unilateral cortical stimulation 30 min before sacrifice led to bilateral widespread and intense Fos induction throughout the normal striatum, although the response was somewhat more intense ipsilaterally and in the dorsolateral rostral striatum. In adult rats whose striatum had been lesioned with ibotenic acid 10-12 days prior to implantation of fetal striatal tissue, 3- and 18-month-old striatal grafts showed Fos immunoreactivity in a considerable number of cells after either bilateral, or ipsilateral (approximately 30-40% of the density of Fos-immunoreactive cells in the normal striatum) or contralateral cortical stimulation. Double-Fos and -DARPP-32 immunohistochemistry revealed that the Fos-immunoreactive nuclei were concentrated in the DARPP-32-positive (i.e. striatum-like) patches, which contained approximately 60% of the density of Fos-positive nuclei in the normal striatum after either ipsilateral or bilateral stimulation. However, Fos-immunoreactive nuclei were unevenly distributed within the DARPP-32-positive compartment of the graft, with some clusters of Fos-immunoreactive nuclei at 2-3 x the density observed in the normal striatum and other areas with Fos-immunoreactive nuclei present at lower density or absent. Fos induction was also observed in 4-week-old grafts, indicating that functional corticostriatal synaptic contacts develop rapidly. Striatal grafts implanted either in non-lesioned host striatum or in long-term (18 months) lesioned striatum, similarly showed Fos-positive nuclei after cortical stimulation, indicating that host corticostriatal fibers are equally capable of establishing functional synaptic contacts under these conditions. These results indicate that host corticostriatal fibres not only form an axonal network within the graft but also induce postsynaptic responses which may contribute to the observed graft-induced amelioration of lesion-derived behavioural deficits.

Animals↗

PubMed1994

Comparison between normal developing striatum and developing striatal grafts using drug-induced Fos expression and neuron-specific enolase immunohistochemistry.

The cell-level functional maturation of cell suspension grafts from embryonic day 14-15 rat striatal primordia implanted unilaterally into ibotenic acid lesioned striata of adult female rats was studied from two days to 10 weeks post-grafting. The functional and morphological characteristics of the grafts were compared with those of adult grafts (one year after implantation), normal adult striata and postnatal developing striata (up to four weeks after birth). Serial sections were stained with Cresyl Violet and investigated immunohistochemically with antibodies against dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein (DARPP-32, as a striatal marker), tyrosine hydroxylase (as a marker of dopaminergic fibres), Fos protein (as a cell-level marker of functional dopaminergic host-graft interactions), and neuron-specific enolase (correlated to differentiation and functional maturation of neuronal cells). Selected sections were double-stained for DARPP-32 and either tyrosine hydroxylase, Fos or neuron-specific enolase. The rats used to study dopamine receptor-activated expression of Fos were killed 2 h after administration of either the dopamine-releasing agent D-amphetamine (5 mg/kg intraperitoneally) or the dopamine-receptor agonist apomorphine (0.25 mg/kg subcutaneously, at which dosage it is active only on supersensitive receptors of denervated neurons). In normally developing rats, amphetamine induced Fos expression in both the striatum and globus pallidus by two weeks after birth; by four weeks, the pattern of amphetamine-induced Fos immunoreactivity was similar to that observed in adults. In the globus pallidus of both two- and three-week-old rats, amphetamine induced greater expression of Fos than in adults. Apomorphine did not induce appreciable Fos activation in either the striatum or the globus pallidus at any stage of development. In striatal grafts, amphetamine induced Fos expression from three weeks after implantation onwards, and by five to 10 weeks post-grafting the pattern of Fos immunoreactivity was similar to that observed in adult grafts. However, apomorphine induced a considerable number of Fos-positive nuclei in striatal grafts at three and four weeks after grafting. Neuron-specific enolase immunoreactivity was moderate in normal adult striatum and very high in the adult globus pallidus, and mainly located in neuronal perikarya and processes. Before two weeks of age, most neuron-specific enolase immunoreactivity was observed in internal capsule fascicles and the striatal afferents. Between two and four weeks after birth, neuron-specific enolase immunoreactivity in striatal and globus pallidus neurons gradually increased, while that in afferent fibres decreased to adult levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1991

[Soy and corn flour precooked with microwaves and its use in the preparation of arepas].

Unhusked corn and soy grits were used as raw material, with a particle size ranging between 10 and 20 mesh (ASTM). The results obtained in this study reveal that microwave heating is effective in destroying the antinutritional factors present in soybeans. The trypsin inhibitor activity, in effect, was reduced to a 76% inactivation. The hemagglutinating titer was labile to the heating process, showing values of +8 to +3 for the full-fat soy flour and precooked soy flour, respectively. The quality of soy protein was measured by the protein efficiency ratio (PER) showing values of 2.63 for the precooked soy flour, and 2.46 to 2.21 for the precooked corn:soy blends (70:30 and 50:50). These uncooked blends present values of 1.17 and 1.04. The enriched corn:soy flour had a PER value of 1.60, in comparison to casein (PER = 2.90). The microwave heating improved the digestibility of the soy flour and blends. There were no significant differences (P less than or equal to 0.05) in relation to the functionality of the precooked flour and mixtures. The results obtained revealed that the applied process markedly improve the functional properties and nutritional value of the enriched flour, and of the "arepas" prepared from them.

Analysis of Variance↗

PubMed1984

[Obtaining protein fractions from commercial sesame cakes (Sesamum indicum)].

Sesame press cake represents an important potential protein source for human consumption. Some of the limiting factors are its high crude fiber content, oxalic acid content, and its bitter taste. By fractionation of solvent-extracted sesame meal, several preparations were obtained which were analyzed for their nutrient content, protein utilization and digestibility. PER values were low, and supplementation with lysine, skim-milk powder, soymeal or fish meal, improved the PER values considerably. Based on these findings, formulas for use as a protein supplement for children are presented.

Amino Acids, Essential↗

PubMed1981

[Formulation of a rice-based beverage of high nutritive value].

The purpose of this work was the production of a beverage with a nutritive value similar to that of milk, but available at a lower cost. A traditional beverage in Venezuela, "Chicha de Arroz" (Rice Chicha), was chosen. The various formulas studied were based on rice, non-fat milk and different kinds of soy flour, in addition to sugar, vegetable oil, vitamins, ferrous sulfate and different flavors. A product with protein and caloric values similar to those of milk was obtained. Twenty formulas were prepared and submitted to physico-chemical, microbiological and sensorial evaluations with respect to flavor, color, viscosity and stability during period of refrigeration. The most adequate formula was prepared on a pilot-plant scale. Rat assays gave the same PER results as those of casein. Consumer acceptability was tested on 1,080 school children, and showed to be greater than 95%. The stability was superior to that of milk and the cost, approximately three-fourths that of the latter. In the school-snack program of the National Institute of Nutrition, milk is now being replaced by this Chicha.

Amino Acids↗

PubMed1975

[Nutritional studies with rice bran].

The nutritional value and proximate chemical composition of five samples of rice bran taken from different varieties of rice grown in Venezuela was studied. Thiamin, niacin, riboflavin and tryptophan, lysine, methionine and cystine were analyzed. The apparent protein digestibility was between 59 an 74%, and the Protein Efficiency Ratio (PER) between 1.19 and 2.31. The supplementation with threonine increased the Protein Efficiency Ratio in 12%, but supplementation with tryptophan did not improve it neither alone nor combined with threonine. Combinations with corn and soyflour that simulate formulas for infants showed that there is a protein supplementation in these mixtures. Some combinations with corn, soy flour, and rice bran had the same P.E.R. as casein. The rice bran is an excellent source of vitamins and minerals in these combinations. The results showed that rice bran has potential value for human consumption.

Food, Fortified↗

PubMedDate not supplied

[Evaluation of the acceptability of a formula for children with diarrhea in a marginal community].

Evaluated the acceptability of a nutrition formula consisting of pumpkin-rice chicken and oils; in a marginal community to children between the ages of 7 months to 5 years old when acute diarrhea was present. The acceptability was also evaluated in the mothers, who indicated that they liked food very little. Nevertheless, they admitted that they would give the product to their children. During the period of study 26 cases of diarrhea were reported of the 26 children, 6 children consumed all the food offered, 16 children showed variable acceptance and only 4 children reject the food completely. By age-groups, the acceptability was 75.69% for children between the ages of 7 months to one year. 72.90% acceptability for ages between 13 months to 2 years and 78.28% for ages between 25 months to 5 years old. The total acceptability was 75.66%. All cases presented marked decreased in diarrhea and an increased in the consistency of the feces with the third dose.

Acute Disease↗