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Biomedical subjects

L Rocha

Publications and source records attributed to L Rocha.

At least 19 recordsLinked to original sources
PubMed2007

Autotaxin (NPP-2) in the brain: cell type-specific expression and regulation during development and after neurotrauma.

Autotaxin is a secreted cell motility-stimulating exo-phosphodiesterase with lysophospholipase D activity that generates bioactive lysophosphatidic acid. Lysophosphatidic acid has been implicated in various neural cell functions such as neurite remodeling, demyelination, survival and inhibition of axon growth. Here, we report on the in vivo expression of autotaxin in the brain during development and following neurotrauma. We found that autotaxin is expressed in the proliferating subventricular and choroid plexus epithelium during embryonic development. After birth, autotaxin is mainly found in white matter areas in the central nervous system. In the adult brain, autotaxin is solely expressed in leptomeningeal cells and oligodendrocyte precursor cells. Following neurotrauma, autotaxin is strongly up-regulated in reactive astrocytes adjacent to the lesion. The present study revealed the cellular distribution of autotaxin in the developing and lesioned brain and implies a function of autotaxin in oligodendrocyte precursor cells and brain injuries.

Animals↗
PubMed2006

Hyperthermia-induced seizures modify the GABA(A) and benzodiazepine receptor binding in immature rat brain.

Effects of hyperthermia-induced seizures (HS) on GABA(A) and benzodiazepine (BDZ) receptor binding in immature rat brain were evaluated using in vitro autoradiography. HS were induced in 10-days-old rats by a regulated stream of moderately heated air directed 50 cm above the animals. Rats were killed 30 min, 24 h or 20 days after HS and their brains were used for in vitro autoradiography experiments to determine GABA(A) and BDZ receptor binding. GABA(A) binding was significantly enhanced in all brain areas evaluated 30 min after HS, an effect that endures 24 h and 20 days after seizures. Concerning BDZ receptor binding, a significant increase was detected in entorhinal and perirhinal cortices and decreased in basolateral amygdala 30 min following HS. One day after HS, animals demonstrated enhanced BDZ binding in the cingulate, frontal, posterior parietal, entorhinal, temporal and perirhinal cortices; striatum, accumbens, substantia nigra pars compacta and amygdala nuclei. Twenty days after HS enhanced BDZ binding was restricted in the cingulated, frontal, anterior and posterior parietal cortices, as well as in substantia nigra pars reticulata, whereas decreased values were found in accumbens nucleus and substantia nigra pars compacta. Our data indicate differential effects of HS in GABA(A) and BDZ binding in immature brain. HS-induced GABA(A) and BDZ changes are different from those previously described in experimental models of temporal lobe epilepsy in adult animals.

Age Factors↗
PubMed2006

Indorenate modifies a1-adrenergic and benzodiazepine receptor binding in the rat brain: an autoradiography study.

Indorenate (5-methoxytryptamine-beta-methylcarboxylate) is a 5-HT1A receptor agonist that produces antihypertensive, anxiolytic, antidepressant and anticonvulsant effects. However, there is evidence suggesting that these effects could involve the activation of benzodiazepine (BZD) receptors but not the activation of a1-adrenergic receptors. The goal of this study was to analyse the effect of indorenate on a1-adrenergic and BZD receptor binding in specific rat brain areas by using in-vitro autoradiography. Coronal brain sections from male Wistar rats were used for labelling 5-HT1A (3H-8-OH-DPAT, 2 nM), a1-adrenergic (3H-prazosin, 2 nM) and BZD (3H-flunitrazepam, 2 nM) receptor binding in the presence or absence of indorenate (1 microM). Indorenate totally displaced 3H-8-OH-DPAT binding in all the brain areas evaluated. It decreased 3H-prazosin binding just in the frontal (30%) and sensorimotor (32%) cortices and in the thalamus (21%). Additionally, indorenate diminished 3H-flunitrazepam binding only in the cingulate (16%) and piriform (18%) cortices as well as in the dorsal raphe nucleus (18%). These results confirm that indorenate is a 5-HT1A ligand and suggest the possible participation of a1-adrenergic and BZD receptors in its pharmacological properties.

5-Methoxytryptamine↗
PubMed2005

5-HT1A receptor expression during memory formation.

RATIONALE: It has been reported that 5-HT(1A) receptors modulate learning and memory and diverse pharmacological and genetic evidence supports this notion. Nevertheless, there are few works about expression of these receptors during memory formation. OBJECTIVE: We aimed to determine 5-HT(1A) receptor expression in brain areas of untrained, passive, and autoshaping trained groups of rats. METHODS: Ex vivo receptor autoradiography using the ligand agonist [(3)H]8-hydroxy-2-[di-n-propylamino]tetralin] (8-OH-DPAT) was used. RESULTS: The trained group relative to untrained animals showed increases of 5-HT(1A) receptor expression in 14 brain areas, decrements in 7, and no changes in 12. Thus, in contrast to untrained rats, 5-HT(1A) receptor expression of autoshaping trained rats was augmented in the tubercule olfactory, septal nucleus, nucleus accumbens, caudate putamen, globus pallidus, striate, and parietal (1 and 2), temporal cortex (1 and 3), granular retrosplenial cortex (1), amygdala, and median and dorsal raphe nuclei. In contrast, in the latter group, receptors were decreased in the CA1 area, hypothalamus dorsal, frontal cortex (1 and 3), occipital cortex, cingulate cortex (1 and 2), and cuneiform nucleus. There were significant differences between passive vs trained groups, but not regarding untrained rats, in the lateral olfactory tract, dentate gyrus, CA3 area, ventromedial hypothalamic, lateral hypothalamus, preoptic medial, frontal cortex (2), granular retrosplenial cortex (2), entorhinal cortex (1 and 2), piriform cortex, and substantia nigra. CONCLUSIONS: These data suggest that upregulated, downregulated, and "silence" of 5-HT(1A) receptors in brain areas form part of neural circuits engaged in memory formation by demonstrating a high degree of specificity and memory mapping.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2005

Modifications of 5-HT4 receptor expression in rat brain during memory consolidation.

Pharmacological evidence indicates a specific role of 5-HT(4) receptors on memory function. These receptors are members of G-protein-coupled 7-transmembrane domain receptor superfamily, are positively coupled to adenylyl cyclase, and are heterogeneously located in some structures important for memory, such as the hippocampus and cortical regions. To further clarify 5-HT(4) receptors' role in memory, the expression of these receptors in passive (P3) untrained and autoshaping (A3) trained (3 sessions) adult (3 months) and old (P9 or A9; 9 months) male rats was determined by autoradiography. Adult trained (A3) rats showed a better memory respect to old trained (A9). Using [(3)H] GR113808 as ligand (0.2 nM specific activity 81 Ci/mmol) for 5-HT(4) receptor expression, 29 brain areas were analyzed, 16 areas of A3 and 17 of A9 animals displayed significant changes. The medial mammillary nucleus of A3 group showed diminished 5-HT(4) receptor expression, and in other 15 brain areas of A3 or 10 of A9 animals, 5-HT(4) receptors were increased. Thus, for A3 rats, 5-HT(4) receptors were augmented in olfactory lobule, caudate putamen, fundus striatum, CA2, retrosplenial, frontal, temporal, occipital, and cingulate cortex. Also, 5-HT(4) receptors were increased in olfactory tubercule, hippocampal CA1, parietal, piriform, and cingulate cortex of A9. However, hippocampal CA2 and CA3 areas, and frontal, parietal, and temporal cortex of A9 rats, expressed less 5-HT(4) receptors. These findings suggest that serotonergic activity, via 5-HT(4) receptors in hippocampal, striatum, and cortical areas, mediates memory function and provides further evidence for a complex and regionally specific regulation over 5-HT receptor expression during memory formation.

Age Factors↗
PubMed2005

Hyperthermia-induced seizures modify the GABAA and benzodiazepine receptor binding in immature rat brain.

Effects of hyperthermia-induced seizures (HS) on GABAA and benzodiazepine (BDZ) receptor binding in immature rat brain were evaluated using in vitro autoradiography. HS were induced in 10-day-old rats by a regulated stream of moderately heated air directed 50 cm above the animals. Rats were killed 30 min, 24 h, or 20 days after HS and their brains were used for in vitro autoradiography experiments to determine GABAA and BDZ receptor binding. GABAA binding was significantly enhanced in all brain areas evaluated 30 min after HS, an effect that endures 24 h and 20 days after seizures. Concerning BDZ receptor binding, a significant increase was detected in entorhinal and perirhinal cortices and decreased in basolateral amygdala 30 min following HS. One day after HS, animals demonstrated enhanced BDZ binding in the cingulate, frontal, posterior parietal, entorhinal, temporal, and perirhinal cortices; striatum, accumbens, substantia nigra pars compacta, and amygdala nuclei. Twenty days after HS enhanced BDZ binding was restricted in the cingulated, frontal, anterior and posterior parietal cortices, as well as in substantia nigra pars reticulata, whereas decreased values were found in accumbens nucleus and substantia nigra pars compacta. Our data indicate differential effects of HS in GABAA and BDZ binding in immature brain. HS-induced GABAA and BDZ changes are different from those previously described in experimental models of temporal lobe epilepsy in adult animals.

Animals↗
PubMed2005

Curative isosorbide-5-mononitrate treatment, in opposition to the beneficial preventive one, aggravates the prothrombotic and proconstrictor state in cyclosporine-induced hypertensive rats.

1. The aim of the present study was to evaluate the effect of preventive and curative isosorbide-5-mononitrate (Is-5-Mn) treatment on the development of hypertension, cGMP content, thromboxane (TX) A(2)/prostaglandin (PG) I2 balance, the peripheral serotonergic system, platelet activation, lipid peroxidation and plasma lipids in cyclosporine A (CsA)-induced hypertensive rats. 2. Control, CsA (5 mg/kg per day) and Is-5-Mn (150 mg/kg per day, b.i.d.) rat groups were treated orally over a period of 7 weeks. The preventive Is-5-Mn group (Is-5-Mn + CsA) was first treated for 2 weeks with Is-5-Mn, followed by 7 weeks with both drugs; the curative Is-5-Mn group (CsA + Is-5-Mn) was treated for a period of 7 weeks with CsA and with both drugs for an additional 5 weeks. The control group received oral vehicle. 3. Whereas in the group undergoing preventive treatment the CsA-induced increase in blood pressure (BP), compared with the control group, was avoided, in the group undergoing curative treatment, the increase in BP was even higher. The decreased arterial cGMP content in the CsA group was prevented and reverted when Is-Mn was administered either preventatively or curatively with CsA. Platelet TXA2 production, although unaffected in the Is-5-Mn + CsA group, was significantly higher in the CsA + Is-5-Mn group compared with the group receiving CsA alone. Furthermore, plasma TXA2 was reduced following preventive Is-5-Mn treatment, but was worsened in the group undergoing curative therapy. Aortic PGI2 synthesis was identical in all groups. Consequently, the TXA2/PGI2 ratio was only altered in the CsA + Is-5-Mn group, demonstrating a markedly higher value. In both groups treated simultaneously with CsA and Is-5-Mn, a higher platelet 5-hydroxytryptamine (5-HT) content was obtained compared with CsA treatment alone, but only preventive treatment with Is-5-Mn resulted in a significant reduction in plasma 5-HT. Changes in ADP and collagen-induced platelet aggregation paralleled those of plasma 5-HT and TXA2: the hyperaggregation profile of the CsA group, although partially prevented, was not reverted by simultaneous treatment with Is-5-Mn and CsA. Lipid peroxidation and lipid profile values also worsened in the CsA + Is-5-Mn group compared with the group administered CsA alone. 4. In conclusion, the beneficial effects of concomitant Is-5-Mn and CsA treatment were demonstrated when Is-5-Mn was administered preventatively because not only was arterial hypertension prevented, but platelet aggregation and plasma TXA2 and 5-HT levels were also reduced. In contrast, following curative treatment, the BP, platelet/vascular vasoconstrictor balance, lipid peroxidation and plasma lipids were aggravated, recommending a judicious evaluation of the impact of nitrate therapy throughout the period of its administration.

Animals↗
PubMed2004

Expression of the 5-HT receptors in rat brain during memory consolidation.

Serotonin (5-hydroxytryptamine, 5-HT) system displays more than 14 receptors subtypes on brain areas involved in learning and memory processes, and pharmacological manipulation of specific receptors selectively affects memory formation. In order to begin the search of 5-HT receptors expression during memory formation, in this work, we aimed to determine, by autoradiography (using 3H 5-HT as ligand, 2 nM, specific activity 123 Ci/mmol), 5-HT receptors (5-HTR) expression in passive (untrained) and autoshaping trained (3 sessions) adult (3 months) and old (9 months) male rats. Thus, trained adult rats had better retention than old animals. Raphe nuclei of adult and old trained rats expressed less receptors on medial and dorsal, respectively. Hippocampal CA1 area and dentate gyrus of adult trained rats expressed less 5-HTR, while dentate gyrus of old increased them. Basomedial amygdaloid nucleus in old trained rats expressed more 5-HTR; while in the basolateral amygdaloid nucleus they were augmented in both groups. Training decreased or did not change 5-HTR in caudate-putamen of adult or old animals. The above profile of 5-HTR expression is consistent with previous reports, and suggests that memory formation and aging modulates 5-HTR expression in brain areas relevant to memory systems.

Age Factors↗
PubMed2003

Opioid peptide release in the rat hippocampus after kainic acid-induced status epilepticus.

It has been suggested that kainic acid enhances opioid peptide release. However, no direct evidence exists to support this hypothesis. The main aim of the present study was to determine whether such release occurs in the hippocampus of the rat after status epilepticus induced by kainic acid. Microdialysis experiments revealed significant opioid peptide release in the hippocampus 90-150 min (100%) and 270-300 min (50%) after kainic acid-induced status epilepticus. The peptides released were identified by high-performance liquid chromatography linked to radioimmunoassay as Met-enkephalin, Leu-enkephalin, Dynorphin-A (1-6), and Dynorphin-A (1-8). Reduced extracellular opioid peptide immunoreactivity was detected 28 days after status epilepticus (38% compared with control situation). The present results indicate an important activation of opioid peptide systems by kainic acid-induced status epilepticus. In addition, the reduced hippocampal extracellular opioid peptide levels long-term after kainic acid administration could have important implications for the progressive nature of epileptogenesis.

Animals↗
PubMed2003

Mild thyroid hormones deficiency modifies benzodiazepine and mu-opioid receptor binding in rats.

The effects of a mild hypothyroidism condition on benzodiazepine (BDZ) and mu opioid receptor levels was investigated. Female Wistar rats were randomly divided into two groups: 1) hypothyroid rats (n=7), which received methimazole (60 mg/kg per day) in drinking water for four weeks, and 2) euthyroid rats (n=8), which drank only tap water. Animals were sacrificed and their brains were used for autoradiography experiments. When compared to the euthyroid group, the hypothyroid group presented reduced benzodiazepine receptor binding in medial amygdala (24%) and high mu-receptor levels in frontal (25%), sensorimotor (65%) and temporal (29%) cortices, basolateral amygdala (50%) and ventroposterior thalamic nucleus (49%). The present data suggest that alterations in BDZ and mu-receptor binding could be associated with the higher excitability observed in animals with triiodothyronine (T(3)) deficiency.

Animals↗
PubMed2001

Identification of peptide sequences specific for serum antibodies from human papillomavirus-infected patients using phage display libraries.

Three random phage display peptide libraries were screened with sera from human papillomavirus (HPV)-infected patients to characterize the specificities of antibodies present in patients' sera and to identify molecules that correspond to or mimic natural epitopes; 141 phage clones were randomly selected in three rounds of bioselection and their binding properties were analyzed in ELISA using sera from 36 patients with confirmed HPV 16 infection and 24 healthy control female blood donors. Sixteen of 36 (44%) patients' sera reacted with at least 1 phage clone, and only 2 of 24 female donors' sera showed positive reaction with 1 of the selected clones. We conclude that the combination of various disease-specific epitopes generated by screening of phage display peptide libraries may potentially lead to a multicomponent diagnostic assay for the early detection of HPV infection and precancerous cervical lesions, making possible the prevention of one of the most common cancers in women.

Antibodies, Viral↗
PubMed2001

Effects of chronic morphine and N(6)-cyclopentyl-adenosine administration on kainic acid-induced status epilepticus.

The aim of the present study was to investigate if the upregulation of mu or A(1) receptors modifies the expression of the kainic acid (KA)-induced status epilepticus (SE). Male Wistar rats received one of the following treatments: saline solution (SS) (1 ml/kg, i.p. for 7 days); morphine (M) (20 mg/kg, i.p. for 7 days) or N(6)-cyclopentyl-adenosine (CPA) (1 mg/kg, i.p. for 9 days). Twenty-four hours after the last administration rats were sacrificed. Membranes were obtained mu and and A(1) receptor binding experiments were carried out. Furthermore, an injection of SS (1 ml/kg, i.p.) or KA (10 mg/kg, i.p.) was applied in rats pretreated chronically with M, CPA or SS, 48 h after the last administration. Seizure activity, death rate and a postictal explosive motor behavior were evaluated after KA administration. Chronic M administration increased mu receptor number in hippocampus (115%) and cortex (265%), whereas chronic CPA treatment enhanced A(1) receptor number in hippocampus (55%), amygdala (39%) and cortex (51%). The pretreatment with M facilitated the KA-induced SE and reduced the death rate as well as the postictal explosive motor behavior. The pretreatment with CPA delayed the SE presentation, increased the death rate and decreased the postictal explosive motor behavior. These findings suggest that upregulation of mu receptors enhances the KA seizures, whereas upregulation of A(1) receptors depresses these seizures.

Adenosine↗
PubMed2001

Electrical stimulation for epilepsy: stimulation of hippocampal foci.

Subacute and chronic continuous electrical stimulation at the epileptic focus in the hippocampus or parahippocampal cortex at 130 Hz, 0.21-1.0 ms, 2.5-3.5 V (about 200-300 microA) induces a decrease in focal EEG epileptic interictal activity and also in the occurrence of clinical seizures. This may represent an alternative for the treatment of temporal lobe seizures originated in bilateral independent temporal lobe foci or occurring in patients where one is uncertain whether memory deficit might result from ablative procedures.

Electric Stimulation Therapy↗
PubMed2000

Characterization of benzodiazepine receptor binding in immature rat brain after kainic acid administration.

PURPOSE: To evaluate the effects of status epilepticus on benzodiazepine (BDZ) receptor binding in immature rat brain. METHODS: Twenty-four immature (15 days old) and six adult (90 days old) rats were used in this study. Status epilepticus was induced in immature animals by administration of kainic acid (7 mg/kg intraperitoneal), whereas adults rats received saline. Animals were killed 72 hours or 35 days after treatment, and their brains were used for in vitro autoradiography experiments to determine BDZ binding. RESULTS: In basal conditions and compared with the adult group, immature animals presented reduced BDZ binding in the entorhinal cortex, substantia nigra pars reticulata, and periaqueductal gray. Seventy-two hours after kainic acid-induced status epilepticus, immature rats showed significantly increased BDZ in the frontal (48%), cingulate (39%), sensorimotor (39%), piriform (57%), and entorhinal (59%) cortices, the medial (84%) and basolateral (27%) amygdaloid nuclei, the dentate gyrus (51%), and the substantia nigra pars reticulata (43%). Thirty-five days after status epilepticus, immature rats displayed decreased BDZ binding in the entorhinal cortex (48%), dentate gyrus (36%), and fields CA1, CA2, and CA3 of Ammon's horn (30%). CONCLUSIONS: The present study demonstrates that status epilepticus and temporal lobe epilepsy produce a characteristic pattern of BDZ binding changes in the immature rat brain that differs from the one previously seen in adults.

Age Factors↗
PubMed1999

Antisense oligonucleotides to C-fos reduce postictal seizure susceptibility following fully kindled seizures in rats.

In a previous study we demonstrated that increased FOS expression in the amygdala induced by partial kindling seizures could be attenuated by administering c-Fos specific antisense oligonucleotides. In addition, we found that the administration of c-Fos antisense oligonucleotides at the beginning of the amygdala kindling process facilitated the appearance of stage V kindled seizures. In the present study, we evaluated the effect of the suppression of FOS on the expression and severity of the generalized fully kindled seizures as well as on the susceptibility to additional ictal events during the postictal and interictal periods. We observed that the administration of c-Fos antisense oligonucleotides did not modify the behavioral and electrographic manifestations of generalized stage V kindled seizures. However, c-Fos antisense oligonucleotides significantly reduced the susceptibility to additional ictal events during the postictal refractory period. Hence, the increased FOS protein induced by generalized tonic clonic seizures may participate in postictal mechanisms.

Amygdala↗
PubMed1999

Characterization of benzodiazepine receptor binding following kainic acid administration: an autoradiography study in rats.

Effects of status epilepticus and chronic temporal lobe epilepsy on benzodiazepine (BDZ) receptor binding in the rat brain were evaluated using in vitro autoradiography, 24 h and 40 days after kainic acid (KA) administration (10 mg/kg i.p). One day after KA-induced status epilepticus and in comparison to saline control group, significantly increased BDZ binding was detected in pyriform cortex (53%), whereas decreased binding was found in anterior amygdaloid nucleus (28%), fields CA1-3 of Ammon's horn (25%) and dentate gyrus (27%). Forty days after status epilepticus, significantly BDZ binding augmentation was noticed in dentate gyrus (65%) and in periaqueductal gray dorsolateral (52%), whereas decreased binding was found in medial thalamic nucleus (70%). Our data indicate different patterns of BDZ binding following KA administration, which may depend on the consequences of the status epilepticus (24 h after KA) and temporal lobe epilepsy (40 days after KA) per se.

Animals↗
PubMed1999

Cerebral hemorrhage and apoE.

The epsilon4 allele of apolipoprotein E (apoE) is found more commonly among patients with Alzheimer's disease (AD) than in the normal population. ApoE is associated with brain amyloid, a component of cerebral amyloid angiopathy (CAA), which is both a pathological feature of AD and a frequent cause of lobar intracerebral hemorrhage (ICH). We hypothesized that the frequency of epsilon4 allele is higher in patients with CAA-related ICH than in hypertensive ICH and in the normal population. To test this hypothesis we compared the frequency of apoE alleles in four populations: 24 patients with lobar ICH, 24 matched patients with hypertensive ICH, 24 matched normal controls, and 173 population controls. Although there was a tendency to a higher frequency of apoE epsilon4 in lobar ICH patients, we found no significant differences in the frequency of this allele between the four studied populations. In addition we did not confirm the finding of some authors of a higher frequency of apoE epsilon2 in patients with lobar ICH than in the normal population. Previous studies on the subject are discussed. The relationship between apoE polymorphism and lobar CAA-related ICH remains to be clearly defined.

Aged↗