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Biomedical subjects

A Pazos

Publications and source records attributed to A Pazos.

At least 73 records · Page 4Linked to original sources
PubMed1992

Osmotic stimulation induces changes in the expression of beta-adrenergic receptors and nuclear volume of astrocytes in supraoptic nucleus of the rat.

The influence of osmotic stimulation on the density of beta-adrenoceptor binding sites in the rat supraoptic nucleus (SON) was studied by quantitative autoradiography using 125I-cyanopindolol (ICYP). Increased density of beta-adrenoceptor binding sites was observed in osmotically stimulated rats and also after the suppression of neuronal activation by rehydration of animals. This was mainly due to a significant increase in the concentration of beta 2 binding sites. The overexpression of beta-adrenoceptors occurred concomitantly with nuclear expansion in SON astrocytes. Moreover, the higher concentration of beta-adrenoceptors observed in the ventral portion of the SON largely coincided with the area that showed intense GFAP-immunostaining. These results provide indirect evidence of an astrocytic location of beta-adrenoceptors and also of beta-adrenergic mediation in the structural and functional changes of SON astrocytes.

Animals↗
PubMed1992

Loss of high-affinity alpha 2-adrenoceptors in Alzheimer's disease: an autoradiographic study in frontal cortex and hippocampus.

We assessed, by quantitative autoradiography, the density of high-affinity alpha 2-adrenoceptors in hippocampus and frontal cortex sections from 18 patients dying with Alzheimer's disease (AD) in comparison with a control group of 13 matched cases. The full agonist [3H]bromoxidine (UK-14304) was used as a ligand. In AD brains, the specific binding of [3H]bromoxidine was markedly decreased both in frontal cortex, the reduction ranging from 55% on layer I (P less than 0.0005) to 40% loss on layers IV-VI (P less than 0.01), and in the hippocampus where the mean of alpha 2-receptor loss was 53% both for the CA1 (P less than 0.0005) and the dentate gyrus (P less than 0.005). This dramatic decrease in the density of functional, high-affinity alpha 2-adrenoceptors very probably reflects the neuronal loss described in locus coeruleus of AD brains. The important implications of these findings for the pharmacological treatment of AD are discussed.

Adrenergic alpha-Agonists↗
PubMed1992

Quantitative light microscopic autoradiographic localization of alpha 2-adrenoceptors in the human brain.

In the present work the anatomical distribution of alpha 2-adrenoceptors in the human central nervous system was studied in detail by quantitative autoradiography using the selective alpha 2 agonist [3H]bromoxidine ([3H]UK-14304) as a ligand. Only postmortem tissues from subjects free of neurological disorders were used in this study. Very high or high densities of alpha 2-adrenoceptors were found along layers I and III in non-visual neocortex, layers III and IVc of the visual cortex, CA1 field--stratum lacunosum-moleculare--and dentate gyrus--stratum granularis--at the hippocampal formation, nucleus arcuatus at the hypothalamus, locus ceruleus, nucleus dorsalis of vagus and at the stratum granularis of the cerebellar cortex. Relevant densities of alpha 2-adrenoceptors were also observed along the remaining layers of neocortex, nuclei centralis, medialis and corticalis at the amygdala, anterior thalamic group and rotundocellularis nuclei, paraventricular and ventromedial hypothalamic nuclei, substantia innominata, superior colliculus--stratum zonale--and lateral periaqueductal area at the midbrain, nucleus tractus solitarii and dorsal horn--substantia gelatinosa--of the spinal cord. [3H]Bromoxidine specific binding was very low or negligible in the remaining brain areas. Although a general parallelism between the distribution of these receptors could be observed for the rat and human brain, dramatic species differences in the level of alpha 2-receptors were found in several brain areas, such as thalamus, amygdala or cerebellar cortex. In general, the distribution of alpha 2-adrenoceptors in the human brain found here was parallel to that described for the noradrenergic presynaptic terminals in the mammalian central nervous system, lending some weight to the proposed predominant presynaptic localization of these receptors. The relevance of the anatomical distribution of alpha 2-adrenoceptors in the human brain for a better knowledge of the neurochemistry of neuropsychiatric disorders is discussed.

Aging↗
PubMed1992

Affinity changes in muscarinic acetylcholine receptors in the rat brain following acute immobilization stress: an autoradiographic study.

The modifications in rat brain muscarinic acetylcholine receptors induced by acute immobilization stress lasting 10 min or 2 h were analyzed by quantitative in vitro autoradiography. [3H]N-Methylscopolamine ([3H]NMS) was used as a ligand. Immobilization stress for 10 min did not produce any significant change in the properties of [3H]NMS binding sites throughout the brain. In contrast, 2 h immobilization caused a significant increase in receptor affinity (Kd) without modification in the maximal number of receptors (Bmax) in several brain areas such as the caudate-putamen, cortical layers and CA1 field of the hippocampus, among others. These results, found even in animals killed immediately after the end of the immobilization sessions, suggest that immobilization stress induces supersensitivity of muscarinic receptors in certain cholinergic pathways in rat brain.

Animals↗
PubMed1992

Dopamine D1 and D2 receptors in progressive supranuclear palsy: an autoradiographic study.

Dopamine D1 and D2 receptors were studied in brain tissue sections from a typical patient with progressive supranuclear palsy and in 7 age-matched brains. The density of D1 receptors in the caudate-putamen and frontal cortex of the patient was within control limits. By contrast, the density of nigral D1 receptors and striatal D2 receptors was dramatically reduced in the patient as compared to the control brains. This work shows again that the loss of striatal D2 receptors is the most plausible explanation for the poor response to dopaminergic drugs in patients with progressive supranuclear palsy. While the loss of nigral D1 receptors can be explained by the loss of nigral neurons, it seems that neurons bearing striatal D1 receptors are spared in progressive supranuclear palsy. The clinical effects of selective D1 agonists are worth testing in this devastating disorder.

Atrophy↗
PubMed1991

Regionally specific age-dependent decline in alpha 2-adrenoceptors: an autoradiographic study in human brain.

The effect of sex, postmortem delay and aging on alpha 2-adrenoceptor binding was studied in tissue sections from several representative regions of the human brain from 21 subjects using [3H]UK-14304 as a ligand. Sex and postmortem delay did not influence the density of alpha 2-receptors. Aging resulted in clear decreases in most forebrain areas examined (n. basalis greater than basal ganglia greater than hypothalamus greater than fronto-temporal cortex greater than hippocampus greater than visual cortex), whereas alpha 2-receptors did not significantly change with age in the amygdala and several infratentorial areas. We conclude that age-related, regionally specific decreases in the density of alpha 2-receptors occur in the human brain. The implications of these findings for age-dependent noradrenergic degeneration are discussed.

Adrenergic alpha-Agonists↗
PubMed1991

High-affinity choline uptake carrier in Alzheimer's disease: implications for the cholinergic hypothesis of dementia.

We examined the density and the state of affinity of [3H]hemicholinium-3 ([3H]HC-3) binding sites, a marker of the presynaptic high-affinity choline uptake (HACU) carrier, in 4 representative regions of 13 postmortem Alzheimer's disease (AD) brains, as well as in 12 matched control brains. Significant reductions in the densities of [3H]HC-3 binding sites were found both in frontal cortex (-44.7%) and hippocampus (-36.5%) of AD brains in comparison to controls. On the other hand the densities of [3H]HC-3 binding sites in AD brains in caudate-putamen and cerebellar cortex showed no significant differences when compared to controls. No significant change in the state of affinity of these sites could be observed in the saturation assays carried out in hippocampus and frontal cortex. Our findings concur with the reported data by using other presynaptic cholinergic markers in AD and confirm that some degree of cholinergic degeneration, highly specific for the basal forebrain neurons, occurs in AD. However, these results, obtained in a group of AD brains belonging to severely demented patients, do not show a dramatic loss of the HACU in many AD brains. Although this fact could be due to the existence of a compensatory mechanism, our results probably suggest that dementia in AD cannot be explained only by the loss of neocortical cholinergic presynaptic terminals arising from the basal forebrain and also may clarify as to why the acetylcholine precursors or the muscarinic agonists are not effective in AD dementia.

Aged↗
PubMed1991

Presynaptic parkinsonism in olivopontocerebellar atrophy: clinical, pathological, and neurochemical evidence.

The substrate for olivopontocerebellar atrophy parkinsonism is obscure due to the lack of clinical and pathological reports and the absence of studies on dopamine receptors in this entity. We describe a patient with olivopontocerebellar atrophy whose clinical presentation was levodopa-responsive parkinsonism in whom pathological examination disclosed pronounced nigral cell loss with no striatal damage. Autoradiographic labeling with 3H-spiperone showed normal densities of D2 dopamine striatal receptors. These data show that indistinguishable nigral, presynaptic parkinsonism occurs in patients with idiopathic Parkinson's disease and in patients with olivopontocerebellar atrophy, and also how a favorable response to levodopa is neither synonymous with idiopathic Parkinson's disease, nor does it exclude multiple-system, atrophy-related parkinsonism.

Aged↗
PubMed1991

Further studies on the biochemical characterization and autoradiographic distribution of [3H]hemicholinium-3 binding sites in rat brain: a presynaptic cholinergic marker.

Hemicholinium-3 (HC-3) is a potent inhibitor of the high-affinity choline uptake system (HACU). Here we report on the biochemical characterization and autoradiographic distribution of [3H]hemicholinium-3 binding sites in rat brain, confirming and expanding results from previous studies. The binding of [3H]HC-3 to striatal membranes was specific, to a single site, sodium-dependent, saturable, and of high-affinity, Kd values being about 3 nM for striatum, 5 nM for the hippocampus and 12 nM for neocortex. [3H]HC-3 specific binding exhibited a pharmacological profile suggestive of physiologically relevant interactions and fully comparable to that reported for HACU. The uneven distribution of [3H]HC-3 binding sites exhibited a high degree of correspondence with the reported distribution of HACU and other enzymatic presynpatic cholinergic markers. The punctual differences between our study and previous works on [3H]HC-3 binding are analysed. We conclude that [3H]HC-3 labelling may be used as a selective and quantifiable marker of the cholinergic presynaptic terminals in close relationship with HACU.

Animals↗
PubMed1990

Autoradiographic localization of alpha 2-adrenoceptors in chick brain.

alpha 2-Adrenoceptors were localized in the chick brain by 'in vitro' receptor autoradiography using [3H]UK 14304 as a ligand. High or very high densities of binding sites were found in the hyperstriatum, tuberculum olfactorium, hypothalamic nuclei, tectum opticum and some medullary nuclei. Comparatively, intermediate densities were observed over the thalamic nuclei and locus ceruleus, among others. Low densities of alpha 2-adrenoceptors were detected in the paleostriatum, hippocampus and cerebellum. Our data indicate that alpha 2-adrenoceptors in the chick brain present similar properties and homologous anatomical distribution to those reported in mammalian brain.

Adrenergic alpha-Agonists↗
PubMed1990

Autoradiographic studies of neurotransmitter receptors in the brain of newborn infants with Down syndrome.

The autoradiographic pattern of cholinergic muscarinic receptors in the brain of two newborn infants with Down syndrome (DS) (stillbirths, 31 and 39 gestational weeks), were compared with that of age-matched control fetuses. Densities and distribution patterns of muscarinic receptors in the forebrain were similar in both groups. However, a marked receptor reduction was found in the midbrain (superior colliculus, substantia nigra) of DS brains compared to control brains. The results indicate the existence of deficient prenatal development of cholinergic transmission in DS that may be responsible for the occurrence of specific difficulties in early postnatal life.

Autoradiography↗
PubMed1990

Characterization of [3H]hemicholinium-3 binding sites in human brain membranes: a marker for presynaptic cholinergic nerve terminals.

We report here on the binding properties of [3H]hemicholinium-3, a selective inhibitor of the high-affinity choline uptake process, to human brain membranes. Under the assay conditions described, the binding of [3H]hemicholinium-3 exhibited a dependency of physiological conditions on pH, temperature, and NaCl concentrations. Striatal binding proved to be specific, to a single site, saturable, and reversible, with an apparent KD of 10 nM and a Bmax of 82 fmol/mg of protein. [3H]Hemicholinium-3 specific binding exhibited a pharmacological profile and an ionic dependency suggestive of physiologically relevant interactions and comparable with those reported for the high-affinity choline uptake. Moreover, specific [3H]hemicholinium-3 binding exhibited an uneven regional distribution: striatum much greater than nucleus basalis greater than spinal cord much greater than midbrain = cerebellum greater than or equal to hippocampus greater than neocortex = anterior thalamus greater than posterior thalamus much much greater than white matter. This distribution closely corresponds to the reported activity of both enzymatic cholinergic presynaptic markers and high-affinity choline uptake in mammalian brain. There are no significant differences between these results and those previously found in the rat brain using this radioligand. Our results demonstrate, for the first time, the presence of [3H]hemicholinium-3 binding sites in human brain and strongly support the proposal that this radioligand binds to the carrier site mediating the high-affinity choline uptake process on cholinergic neurons. Thus, [3H]hemicholinium-3 binding may be used in postmortem human brain as a selective and quantifiable marker of the presynaptic cholinergic terminals.

Aged↗
PubMed1989

Autoradiographic distribution of [3H]hemicholinium-3 binding sites in human brain.

Since previous radioligand binding studies support the evidence that [3H]hemicholinium-3 ([3H]HC-3) selectively labels the high-affinity choline uptake (HACU) process, we have studied the autoradiographic characteristics and regional distribution of [3H]HC-3 binding to post mortem human brain tissue. [3H]HC-3 specific binding was saturable, of high affinity and exhibited an uneven distribution. High densities were observed in caudate-putamen, nucleus basalis accesorius of the amygdala, hippocampal gyrus dentatus and CA3 field, locus niger, nucleus interpeduncularis and motor trigeminal and facial nuclei. Low densities were found in areas such as neocortex, thalamus, hypothalamus or cerebellum. Our results agree with those obtained in human brain membranes and are comparable to previous autoradiographic data from rat brain. Remarkably, the distribution of [3H]HC-3 binding sites closely corresponds with that of cholinergic enzymatic presynaptic markers and HACU. These findings, together with previous data from membrane studies, allow the use of [3H]HC-3 as a selective anatomical marker of cholinergic presynaptic terminals.

Aged↗
PubMed1989

Dopamine receptors in human brain: autoradiographic distribution of D1 sites.

The distribution of dopamine D1 receptors has been determined in post mortem human brain tissues using in vitro receptor autoradiography, with ([3H]N-methyl) SCH 23390 as ligand. The highest densities of dopamine D1 sites were seen in the nucleus caudatus, putamen, globus pallidus pars medialis and substantia nigra. Intermediate densities were associated with the amygdala, mammillary bodies, cerebral cortex and CA1. The remaining part of the hippocampus as well as the diencephalon, brainstem and cerebellum contained low levels of [3H]SCH 23390 binding sites. The distribution of D1 receptors in the human brain closely resembles that reported for the rat brain. In addition, there was a good correlation between the anatomical localization of D1 sites and the distribution of dopaminergic nerve terminals in the central nervous system. The densities of D1 receptors in the human brain were observed to markedly decrease with age during the first decades of life. However, no further modifications were found beyond the age of 40 years. We did not observe any significant influence of other parameters such as gender and post mortem delay in our samples.

Aging↗
PubMed1988

Alpha 2-adrenoceptors in human forebrain: autoradiographic visualization and biochemical parameters using the agonist [3H]UK-14304.

The regional distribution and biochemical parameters of alpha 2-adrenoceptors in post-mortem human brain tissue were analyzed in autoradiographic and membrane binding studies, using the full agonist, [3H]UK-14304. Autoradiographic visualization of these receptors in the forebrain revealed a heterogeneous anatomical distribution with high levels in the neocortex, ventral hypothalamus, hippocampus and some thalamic nuclei, among others. In membrane binding studies, analyses of saturation curves indicated the presence of a single population of sites for [3H]UK-14304 both in the human and rat brain. There was a good correlation between the density of alpha 2-adrenoceptors obtained by both procedures. [3H]UK-14304 is a feasible ligand to localise and quantify alpha 2-adrenoceptors in human post-mortem material by autoradiographic and membrane binding techniques.

Aged↗
PubMed1988

Identification of a 5-HT1 recognition site in human brain membranes different from 5-HT1A, 5-HT1B and 5-HT1C sites.

In human caudate and cortex membranes, [3H]serotonin ([3H]5-HT) labels 5-HT1A and 5-HT1C recognition sites which show nanomolar affinity for 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) and mesulergine respectively, whereas no 5-HT1B binding could be identified. However, the majority of the sites labelled by [3H]5-HT (greater than or equal to 60% in cortex, 90% in caudate) are different from 5-HT1A, 5-HT1B and 5-HT1C sites. Competition experiments were performed in human caudate membranes incubated with [3H]5-HT in the presence of 100 nM 8-OH-DPAT and 100 nM mesulergine. Under those conditions, [3H]5-HT labelled an apparently homogeneous population of 5-HT1-like sites which display nanomolar affinity for tryptamines (5-carboxamido-tryptamine, (5-CT) greater than 5-HT greater than or equal to 5-methoxytryptamine (5-MeOT) greater than tryptamine) and some ergolines (metergoline greater than methysergide). In contrast, these sites showed low affinity for drugs with high affinity and/or selectivity for 5-HT1A (8-OH-DPAT, buspirone), 5-HT1B (21-009, RU 24969), 5-HT1C (mesulergine, mianserin) and 5-HT2 sites (ketanserin, cinanserin). The pharmacological profile of these sites is different from that of 5-HT1A, 5-HT1B, 5-HT1C, 5-HT2 and 5-HT3 sites but is consistent with the pharmacology of a 5-HT1-like receptor. It is very similar to that of the 5-HT1D site recently described in bovine brain by Heuring and Peroutka.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

The ontogeny of brain neurotensin receptors studied by autoradiography.

Using in vitro receptor autoradiographic techniques we have analysed the pre- and postnatal development of neurotensin receptors in the rat brain. Receptors were labeled with [3H] or [125I]neurotensin in mounted tissue sections from animals of ages gestational day 14 until the postnatal day 21 as well as young adult animals. Very low densities of neurotensin receptors were visualized on gestational days 14 and 15. Between gestational days 16 and 18 a marked increase in the density of neurotensin receptors was seen in the developing neocortex. Densities in other brain areas, particularly the midbrain and brainstem were much lower than cortical densities. The density of neurotensin receptors in the cortex increased through the last part of the gestation and early postnatal life until it peaked at the end of the first postnatal week. After that, neurotensin receptor binding decreased dramatically reaching lower densities seen in the adult animal at the end of the third postnatal week. Development of neurotensin receptors in other brain areas followed very different time patterns. Neurotensin receptors in the midbrain were seen first at gestational day 18 and increased slowly with development to reach adult levels at about the second week of postnatal life. Neurotensin receptors in the hippocampal formation demonstrated postnatal development; they were detected at postnatal day 5 and showed a developmental peak around the second week. These patterns were seen with both 3H- and 125I-labeled neurotensin, thus excluding possible differential quenching artifacts. These clear differential regional ontogenetic patterns for neurotensin receptors are the main findings of these experiments. The very high densities present in the cortex even in fetal stages suggest that neurotensin could play a role in the development of the brain.

Animals↗