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J Bernal

Publications and source records attributed to J Bernal.

At least 91 records · Page 5Linked to original sources
PubMed1993

Brain-specific prostaglandin D2 synthetase mRNA is dependent on thyroid hormone during rat brain development.

We have previously described several cDNA clones whose expression is affected by thyroid hormone during rat brain development. We now report the identification of one of these, the E2 clone, as the brain-specific prostaglandin D2 (PGD2) synthetase gene. Sequence comparison shows a nearly complete identity between the 356 nucleotides of the E2 clone and nucleotides 403 to 759 of PGD2 synthetase cDNA. The pattern of E2 expression corresponds to that expected for brain specific PGD2 synthetase gene, i.e. the corresponding mRNA is not detected in any other tissue analyzed apart of the brain, and it was present at different levels in all brain regions. Hypothyroidism decreased E2 mRNA concentrations in cerebral cortex and cerebellum. Control of the level of expression of PGD2 synthetase gene may contribute the complex effects of thyroid hormone on brain development and function.

Animals↗
PubMed1993

Antimalarial drugs inhibit calcium-dependent backward swimming and calcium currents in Paramecium calkinsi.

The antimalarial drugs, quinacrine, chloroquine, quinine, primaquine, and mefloquine, share structural similarities with W-7, a compound that inhibits calcium-dependent backward swimming and calcium currents in Paramecium. Therefore, we tested whether antimalarial drugs also inhibit backward swimming and calcium currents in P. calkinsi. When the Paramecium is depolarized in high potassium medium, voltage-dependent calcium channels in the ciliary membrane open causing the cell to swim backward for 30 to 70 s. Application of calcium channel inhibitors, such as W-7, reduce the duration of backward swimming. In 0.05 mM calcium, quinacrine, mefloquine, quinine, chloroquine, primaquine and W-7 all reduced the duration of backward swimming. These effects were seen in sodium-containing and sodium-free high potassium solutions as well as sodium-free depolarizing solutions containing potassium channel blockers. In these low calcium solutions, backward swimming was inhibited by 50% at concentrations ranging from 100 nM to 30 microM. At higher calcium concentrations (1 mM or 15 mM), the effects of the antimalarials and W-7 were reduced. The effects of quinacrine and W-7 were tested directly on calcium currents using the two microelectrode voltage clamp technique. In 15 mM calcium, 100 microM quinacrine and 100 microM W-7 reduced the peak calcium current by 51% and 42%, respectively. Thus, antimalarial drugs reduce calcium currents in Paramecium calkinsi.

Animals↗
PubMed1993

Correlation between computed tomography and voltage and current source density spectral EEG parameters in patients with brain lesions.

In a group of patients with space-occupying brain lesions, CT measurements were correlated with absolute power (AP) and relative power (RP) of the delta, theta, alpha and beta EEG bands, calculated from the raw EEG potentials (EEGp) and from the Laplacian estimates also called "current source densities" (CSD). Rank correlations were calculated between the number of abnormal values in each band and the following CT measures: volume of the lesion and of the edema, density of the edema, percentage of ventricular collapse and midline shift. Abnormal spectral values are those which are significantly higher than the norm for the same age, in the delta and theta bands, and significantly lower in the alpha and beta bands. Spectral parameters obtained from the CSD showed higher correlations with CT measures than those calculated from the EEGp. In the Laplacian, all CT measures had a significant correlation with delta AP. Theta AP was significantly correlated with the volume and density of the edema, as well as with midline shift. Significant correlations were also observed with delta and alpha RP. However, changes in RP were considered to be a consequence of the increase in delta AP. Canonical correlation analyses between AP and RP calculated from EEGp or CSD and the first 3 CT measures showed that the volume of the lesion was only correlated with delta AP and RP. The volume and density of the edema showed a significant correlation with delta, theta and alpha AP calculated from EEGp and only with theta and alpha AP in the Laplacian. Since the EEGp tends to produce a more extensive and diffuse picture of abnormality, whereas the Laplacian acts as a spatial filter emphasizing local sources over distant sources, we concluded that edema is related not to delta activity, but to the theta and alpha power.

Adolescent↗
PubMed1993

Thyroid hormone receptor/c-erbA: control of commitment and differentiation in the neuronal/chromaffin progenitor line PC12.

The c-erbA proto-oncogenes encode nuclear receptors for thyroid hormone (T3), a hormone intimately involved in mammalian brain maturation. To study thyroid hormone receptor (TR) action on neuronal cells in vitro, we expressed the chicken c-erbA/TR alpha-1 as well as its oncogenic variant v-erbA in the adrenal medulla progenitor cell line PC12. In the absence of T3, exogenous TR alpha-1 inhibits NGF-induced neuronal differentiation and represses neuron-specific gene expression. In contrast, TR alpha-1 allows normal differentiation and neuronal gene expression to occur in the presence of T3. Finally, TR alpha-1-expressing cells become NGF-responsive for proliferation when T3 is absent, but NGF-dependent for survival in presence of T3. A similar differentiation induction by NGF plus T3 was observed in a central nervous system-derived neuronal cell line (E 18) expressing exogenous TR alpha-1. Together with the finding that TR alpha-1 constitutively blocked dexamethasone-induced differentiation of PC12 cells into the chromaffin pathway, these results suggest that TR alpha-1 plays an important role in regulating commitment and maturation of neuronal progenitors. In contrast, the v-erbA oncogene, a mutated, oncogenic version of TR alpha-1, partially but constitutively inhibited NGF-induced neuronal differentiation of PC12 cells and potentiated dexamethasone-induced chromaffin differentiation, giving rise to an aberrant "interlineage" cell phenotype.

Animals↗
PubMed1993

Neonatal hypothyroidism affects the timely expression of myelin-associated glycoprotein in the rat brain.

Congenital hypothyroidism strongly affects myelination. To assess the role of thyroid hormone on myelin gene expression, we have studied the effect of hypothyroidism on the steady state levels of myelin-associated glycoprotein (MAG) and its mRNA in rat brain during the first postnatal month. As studied by immunoblot analysis of several brain regions, MAG increased from days 10-15 onwards, reaching constant levels by days 20-25. Hypothyroid samples showed a delay in the accumulation of MAG that was more severe in rostral regions, such as cortex and hippocampus. The effect of hypothyroidism on the accumulation of the protein correlated with mRNA levels. MAG mRNA started to accumulate in the cerebrum of normal animals by postnatal day 7, reaching maximal levels by day 20. Hypothyroid rats showed a delay of several days in the onset of mRNA expression, increasing thereafter at the same rate as in normal animals, and eventually reaching similar values. When individual brain regions were analyzed, we found strong regional differences in the effect of hypothyroidism. The cerebral cortex was most affected, with messenger levels lower than in normal animals at all ages. In more caudal regions differences between control and hypothyroid rats were evident only at the earlier stages of myelination, with spontaneous recovery at later ages. By run on analysis, we found no differences in transcriptional activities of the MAG gene in normal, hypothyroid, or T4-treated rats. Therefore, the effects of hypothyroidism on MAG mRNA and protein levels were most likely caused by decreased mRNA stability. We propose that thyroid hormone contributes to enhanced myelin gene expression by affecting the stability of newly transcribed mRNA in the early phases of myelination.

Aging↗
PubMed1993

Thyroid hormone regulation of RC3, a brain-specific gene encoding a protein kinase-C substrate.

RC3 is a brain-specific mRNA expressed in discrete neuronal groups of the forebrain that encodes a 78-amino acid protein, also called neurogranin, a calmodulin-binding, protein kinase-C substrate. Expression of RC3 mRNA was studied in normal and hypothyroid animals during the first month of life. Hypothyroid rats were produced by administration of methyl-mercapto-imidazol to the pregnant dams and subsequent surgical thyroidectomy on postnatal day 5 of the neonates. As studied by slot-blotting of total cerebrum poly(A)+ RNA, RC3 mRNA accumulates in normal brain from the fifth to seventh postnatal day, reaching maximal levels around days 10-12. RC3 mRNA accumulation in hypothyroid animals was blunted, and the maximal levels attained were about 30-50% of normal values. The effect of hypothyroidism on steady state mRNA levels was also observed by Northern blotting of RNA from cerebral cortex and striatum. As studied by immunoblotting using a polyclonal antibody, hypothyroidism also led to clear decreases in the amount of the RC3 protein in extracts from cerebral cortex, striatum, and hippocampus. A single administration of 10 micrograms T4 to hypothyroid rats on postnatal day 12 led to a steady increase in striatal RC3 mRNA from levels that were about 40% of normal to about 70% of normal at 16 h and 115% of normal at 48 h. In contrast to the effect on RC3, hypothyroidism did not affect developmental expression of the mRNA encoding GAP-43, another brain protein kinase-C substrate of axonal localization. RC3 is, thus, one of the few known neuronal genes whose expression is influenced by thyroid hormone in the brain. Thyroid hormone is required for an appropriate level of expression, not for the developmentally programmed timing of expression of the RC3 gene.

Animals↗
PubMed1993

Guanine nucleotides modulate calcium currents in a marine Paramecium.

Voltage-dependent calcium channels play a critical role in many cell functions and in many cell types ranging from protozoa to vertebrates. We have shown previously that guanine nucleotides modulate the calcium action potential and the duration of backward swimming in Paramecium, both indirect measurements of calcium channel function. To determine whether guanine nucleotides to indeed alter calcium currents, the inward calcium current (ICa) in Paramecium calkinsi was studied. First, the calcium current was characterized. The magnitude of ICa increased as the extracellular calcium concentration was increased from 0.5 to 50 mmol l-1, unlike the situation in freshwater species of Paramecium where the inward calcium current magnitude is maximal when extracellular calcium levels reach 1 mmol l-1. Inorganic compounds (NiCl2 at 10 mumol l-1 and CdCl2 at 1 mmol l-1) and organic compounds (naphthalene sulfonamides, W-7 and W-12-Br at 100 and 2 mumol l-1, respectively) reduced ICa. Regardless of the holding membrane potential (from -80 to -20 mV), the threshold activation for ICa was at -10 mV and the maximum value of ICa was reached at +20 mV, suggesting that there is only one type of calcium channel in P. calkinsi. Second, we injected GTP gamma S, GTP and GDP beta S into voltage-clamped cells while monitoring calcium and/or potassium currents. GTP gamma S increased the magnitude of ICa by 42 +/- 6% (mean +/- S.D., N = 5) and the effect was irreversible, GTP increased the magnitude of ICa by 37 +/- 4% (N = 4) in a reversible manner, and GDP beta S decreased ICa by 57 +/- 8% (N = 3) irreversibly. The outward potassium currents did not change when GTP gamma S was injected into the cells. These results support the hypothesis that injection of guanine nucleotides modulates the voltage-dependent calcium channel in P. calkinsi, presumably by activating G-protein-dependent processes.

Animals↗
PubMed1993

Sex differences in EEG coherence in normal children.

The idea that sex differences in the execution of different mental tasks mean a different cerebral organization met contradictory results. Sex differences in brain electrical activity were reported by various authors. The EEG coherences show functional and anatomical interrelation, so they may reveal differences in brain organization. This paper tries to demonstrate how sex differences are manifested in EEG coherences, in 42 right-handed control children, 18 girls and 24 boys, aged 7.6 to 13.3. Since the effect of age is high on EEG measurements, regression against age was calculated and eliminated. The Z-transformed coherence values were compared by Student's t-test. The results obtained showed that girls had higher right intrahemispheric coherence values than boys in all bands. These sex differences were more numerous in the theta band. The interhemispheric differences were slight and girls had higher coherences in all bands except for the alpha band, where boys had higher interhemispheric coherence than girls. These results show slight but consistent differences in the functional organization of the right hemisphere by sex and reveal the necessity to elaborate separated EEG norms for boys and girls.

Adolescent↗
PubMed1993

Test-retest reliability of EEG spectral parameters during cognitive tasks: I. Absolute and relative power.

We analyzed test-retest reliability of Absolute (AP) and Relative Power (RP) during rest and during two cognitive tasks: one verbal, the search for a synonym, and the other consisting of mental arithmetic calculations. Under all conditions during the experiment the subjects had their eyes open. The experiment was performed twice, with a month's interval between each trial. Monopolar recordings were obtained in F3, F4, C3, C4, P3, P4, O1, O2, F7, F8, T3, T4, T5, T6 and Cz vs A1A2. Differences between sessions were observed mainly during rest with eyes open in the lapha band, with higher AP during the first session. During rest it is extremely difficult to control for the state of vigilance, anxiety and thinking. However, during cognitive tasks a more rigid control of the state of vigilance and thinking is obtained. Therefore, AP and RP are very reliable parameters for analyzing EEG during mental tasks. Comparisons between conditions were also made. The only significant differences observed were in delta AP in the second session, with more power during the cognitive tasks in C3 and O2. MANOVAs using the values of AP in the four bands showed significant differences between conditions in C3, C4, P3, O2 and T4. Several factors that may be involved in the origin of delta activity, including eye movements, slow potential shifts and the inhibition of cholinergic projections to the cortex, are discussed.

Adult↗
PubMed1993

Test-retest reliability of EEG spectral parameters during cognitive tasks: II. Coherence.

We analyzed test-retest reliability of EEG coherence during rest and during two cognitive tasks: one verbal, the search for a synonym, and the other consisting of mental mathematical calculations. The experiment was performed twice, with a month's interval between each session. Coherence between all pairwise combinations of the EEG recorded in 15 leads was computed for delta, theta, alpha and beta bands. Comparing the changes observed between sessions for each condition, few significant changes were observed during rest, and the condition which manifests the most changes was calculation. Differences between conditions were observed in the second session in P3-T5, P3-T6, P3-T3, P4-T6, P4-T5, P4-Cz and Cz-T6 delta coherences ordered in a decreasing order from calculation to synonyms to rest. In order to ascertain whether the pattern of coherences across the head in each subject varied in relation to the session and the condition, we computed the correlation coefficients between all coherences values for one condition versus the other condition per band. For all subjects correlation coefficients near unity were observed between conditions in each session. However, correlation coefficients between sessions, even for the same condition, were much lower. We also computed the correlation coefficients for the coherence values between subjects in the same condition separately for each session. Correlation coefficients between subjects were much higher in the second session than in the first one.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1992

Maturation of the coherence of EEG activity in normal and learning-disabled children.

The age effect on coherence has been studied in control (98) and learning-disabled (LD, 54) school-aged children (from 6.0 to 16.8 years old). The EEG recordings were made at rest in 15 leads, and 105 pairwise combinations for coherence were calculated (each lead was compared with all the rest) for delta, theta, alpha, beta and total frequency bands. A significant increase of coherence with age was found in both groups, with a different pattern of maturation. In the control group, a significant increase with age was found in the coherences between posterior regions and vertex (Cz). A significant decrease with age in the coherence between frontal areas was observed, especially in the theta band. The LD group showed a different pattern: no significant relation with age was found in the coherence between any lead and vertex. A high effect of age on coherence between temporal regions was observed with a predominance of the left side in comparison with the contralateral and the ipsilateral. No decrease in frontal coherence was found: in the same region where the control group showed negative values with age, the LD groups had no age effect. The results obtained are discussed as differences in brain organization, in myelogenesis and synaptogenesis and an explanation of the etiology of LD is proposed.

Adolescent↗
PubMed1992

Adult rat brain is sensitive to thyroid hormone. Regulation of RC3/neurogranin mRNA.

The mammalian brain is considered to be poorly responsive to thyroid hormone after the so called "critical periods" of brain development, which occur in the rat before postnatal days 15-20. In a previous work (Muñoz, A., A. Rodriguez-Peña, A. Perez-Castillo, B. Ferreiro, J.G. Sutcliffe, and J. Bernal. 1991. Mol. Endocrinol. 5:273-280) we have identified one neuronal gene, RC3, whose expression is influenced by early neonatal hypothyroidism and thyroid hormone treatment. In the present work we show that adult-onset hypothyroidism leads to a reversible decrease of RC3 mRNA. Rats thyroidectomized on postnatal day 40 and killed three months later showed a decreased RC3 mRNA concentration in the cerebral cortex and striatum. The same effect was observed in animals made hypothyroid on postnatal day 32 and killed on postnatal day 52. RC3 expression was normal when hypothyroid animals were treated with T4 five days before being killed. In contrast, the mRNA encoding myelin proteolipid protein showed no changes in either experimental situation. RC3 mRNA levels were not affected by food restriction demonstrating that the effect of hypothyroidism was not related to the lack of weight gain. The control of RC3 mRNA is so far the only molecular event known to be regulated by thyroid hormone once the critical periods of brain development are over and could represent a molecular correlate for the age-independent, reversible alterations induced by hypothyroidism in the adult brain.

Age Factors↗
PubMed1992

Visual evoked potentials, attention and mnemonic abilities in children.

We analyzed the correlation between attention and mnemonic processes and different visual evoked potential (VEP) parameters. A group of 34 children between 9 and 13 years old was studied. VEPs were recorded in C3, C4, P3, P4, O1, O2, T5 and T6 with linked ear lobes as reference. Two different types of stimuli were used: flash and checkerboard pattern. The power of VEPs was calculated as the sum of the square amplitude values for different time epochs. Correlation coefficients between left and right homologous VEPs were also computed. A visual selective attention task divided into 5 items of increasing difficulty and the Sternberg paradigm were applied. The performance was automatically evaluated by the computer, giving the number of correct responses (NCR) and other measures of performance. Correlation coefficients between VEP parameters and the scores obtained in the performance of tasks were calculated. It was observed that power in P3, P4, T5, and T6 and the correlation coefficients between central, parietal and temporal VEPs were positively correlated with NCR of both tasks. However, power in O1 and O2 was negatively correlated with NCR.

Adolescent↗
PubMed1992

Influence of thyroid hormone on brain gene expression.

Brain development in mammals is dependent on thyroid hormone. In the rat, the T3 receptor is present as early as the 14th day of fetal life and increases during the periods of neuroblast proliferation and oligodendrocyte differentiation. The mRNAs encoding the receptor isoforms can also be demonstrated by in situ hybridization, with different distribution of the alpha or beta forms. Expression of several genes was studied in hypothyroid animals during the neonatal period. The lack of thyroid hormone affects the expression of most oligodendrocyte genes in a time- and region-dependent fashion. The major role of thyroid hormone on myelin genes is on their timing of expression. Among the neuronal genes studied, thyroid hormone influences the expression of RC3, a brain specific gene encoding a protein kinase C substrate. Thyroid hormone is not require for the timing of expression of this gene, but is needed for its full expression both during the neonatal period and in adult animals.

Animals↗
PubMed1991

Effects of neonatal hypothyroidism on rat brain gene expression.

To define at the molecular biological level the effects of thyroid hormone on brain development we have examined cDNA clones of brain mRNAs and identified several whose expression is altered in hypothyroid animals during the neonatal period. Clones were identified with probes prepared by subtractive or differential hybridization, and those corresponding to mRNAs altered in hypothyroidism were further studied by Northern blot analysis. Using RNA prepared from whole brains, no effect of hypothyroidism was found on the expression of the astroglial gene coding for glial fibrillary acidic protein. Among genes of neuronal expression, no significant alterations were found in the steady state levels of mRNAs coding for neuron-specific enolase, microtubule-associated protein-2, Tau, or nerve growth factor. N-CAM mRNA increased slightly in hypothyroid brains. In contrast a 2- to 3-fold decrease was found in the mRNA coding for a novel neuronal gene, RC3. This is the first neuronal gene known to be significantly altered at the mRNA level by thyroid hormone deprivation. The abundance of the mRNAs for the major myelin proteins proteolipid protein, myelin basic protein, and myelin-associated glycoprotein, expressed by oligodendrocytes, were also decreased in hypothyroid brains. Developmental studies on RC3 and myelin-associated glycoprotein expression indicated that the corresponding mRNAs accumulate in the brain of normal rats during the first 15-20 days of neonatal life. A similar accumulation occurred in hypothyroid brains, but at much reduced levels. The results demonstrate that thyroid hormone controls the steady state levels of particular mRNAs during brain development.

Animals↗
PubMed1991

Independent expression of the alpha and beta c-erbA genes in developing rat brain.

Thyroid hormone is important for normal brain development. Cellular responses to thyroid hormone are mediated by multiple nuclear receptors, classified into alpha- and beta-subtypes. In the rat, expression of both the alpha and beta genes results in several translation products. By using cRNA probes common to alpha transcripts or specific for alpha-1 and beta-1, we have studied the distribution of these transcripts in rat brain at different stages of development from embryonic day 14 to adult age by using in situ hybridization histochemistry. On embryonic day 14, the alpha-1 mRNA is already widely expressed at a low level in the developing brain. The alpha-1 mRNA is developmentally regulated and showed a peak in expression during the first 3 postnatal weeks in the cerebral cortex, amygdala, hippocampus, and cerebellum. The probe common to the alpha transcripts detected a widespread distribution and high levels of these forms in the same regions throughout postnatal development. The level of beta-1 mRNA before birth was low or undetectable. The beta-1 transcript showed developmental regulation as well, with a high level at birth in the mitral cell layer of the olfactory bulb, accumbens nucleus, caudate, and hippocampal field CA1 and increasing levels in other regions later during development. Complementary expression of the alpha and beta forms was seen in the cerebral cortex and hippocampus. The differential temporal and spatial distribution as well as coexpression at comparable levels in certain brain regions suggest different roles for the c-erbA proteins during brain development and in the mature animal.

Age Factors↗
PubMed1991

GTP-gamma-S increases the duration of backward swimming behavior and the calcium action potential in marine Paramecium.

Behavioral and electrophysiological experiments were made to examine the hypothesis that G-proteins modulate the voltage-dependent calcium channel in the marine ciliate Paramecium calkinsi. It was found that guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S), an analogue of GTP that binds to and activates G-proteins, increased the duration of backward swimming behavior in reversibly permeabilized Paramecium in an irreversible and concentration-dependent manner. At 1 mumol l-1 GTP-gamma-S, the duration of backward swimming behavior was increased fivefold. Other nucleotides and related compounds did not have a significant effect on the backward swimming behavior. To evaluate whether the behavioral effects were due to ion channel modulation, the calcium action potential in intact Paramecium was monitored before and after guanine nucleotide injection. Within 5 min after the injection of GTP-gamma-S or GTP into the cell, the duration of the calcium action potential was prolonged at least threefold. Like the behavioral response, the GTP-gamma-S effect on the calcium action potential duration was irreversible, whereas the effect of GTP began to decay after 6 min. GDP-beta-S, which binds to and inactivates G-proteins, markedly reduced the calcium action potential within 5 min after injection. These results support the hypothesis that the voltage-dependent calcium channels present in Paramecium are modulated by GTP-binding proteins.

Action Potentials↗