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Biomedical subjects

M S Magnoni

Publications and source records attributed to M S Magnoni.

At least 19 recordsLinked to original sources
PubMed1991

The aging brain: protein phosphorylation as a target of changes in neuronal function.

There is evidence that senescence affects neurotransmission at different levels. In particular, this review summarizes the studies on age-dependent modifications in protein phosphorylation, which represents the final pathway in the action of transmitters and hormones at neuronal level. Cyclic AMP-dependent protein kinase and protein kinase C have been reported to be modified during aging in various cerebral areas; the changes may involve either enzyme activity or substrate availability. These findings can be related to the alterations in neurotransmitter function and synaptic efficiency observed in the senescent brain. The activity of the other types of protein kinases (tyrosine-, cGMP-, calcium/calmodulin-dependent) during aging needs to be explored. An emerging point is the role of protein phosphorylation in the transfer of membrane signals to the nucleus, for the activation or disactivation of specific genes responsible for long-term neuronal events. Along this view, alterations in protein kinase pathway during senescence would ultimately affect gene expression, resulting in long term modifications of cell function. The reviewed literature opens the perspective of restoring some of the deficits associated with senescence by modulating protein phosphorylation pathway.

Aging↗
PubMed1988

L-type calcium channels are modified in rat hippocampus by short-term experimental ischemia.

Increasing evidence suggests a role for calcium ions in the pathophysiology of ischemic brain damage. The major mechanism allowing calcium entry from the extracellular compartment is the opening of voltage-operated calcium channels. In this line, we have explored the hypothesis that the characteristics of central L-type voltage-dependent calcium channels, labeled by the dihydropyridine ligand 3H-PN 200-110, may be modified by experimental ischemia. The results show that short-term mild ischemia, produced in the rat by 1 h of right carotid ligation, induces an increase in the number of 3H-PN 200-110 binding sites in the hippocampus ipsilateral to the side of carotid occlusion, accompanied by an increase in the dissociation constant value, whereas no changes in the kinetic parameters of the binding were observed in the other areas examined, i.e., the cortex and the striatum. The changes in hippocampus are transient: 96 h after the occlusion, binding parameters return to the control range. The modifications of the binding characteristics in the hippocampus may be related to alterations of Ca2+ fluxes through L-type calcium channels.

Animals↗
PubMed1988

Glial brain tumors lack microvascular adrenergic receptors.

In human and animal brain microvessels beta-adrenergic receptors have been identified which are suggested to subserve the regulation of capillary function in both physiological and pathological conditions. Brain tumors are supplied by vessels that differ from those supplying normal cerebral tissue in various structural and functional parameters. In order to study the characteristics of brain tumor microcirculation, we have investigated the presence of beta-adrenergic receptors in capillaries isolated from different types of neoplasms using the specific radioligand 125I-iodocyanopindolol (ICYP). The microvessels were isolated and prepared by albumin flotation and glass bead filtration from normal and pathological tissues. No ICYP-specific binding was detected in the microvessels of tumors of glial origin, while capillaries obtained from meningiomas and neurinomas showed, like the normal brain, a specific binding of the radioligand. The data indicate that the regulation of capillary function in glial tumors differs from that of normal cerebral tissue and extraparenchymal tumors, thus indicating an impaired control of the vascular permeability.

Brain Neoplasms↗
PubMed1988

The central dopaminergic system: susceptibility to risk factors for accelerated aging.

The synaptic deficit of brain dopaminergic activity involves a complex pattern of changes both at presynaptic and at postsynaptic level. The aged dopaminergic nuclei present a reduced number of dopamine terminals, a decreased ability to synthesize and reuptake dopamine and defective recognition sites both in terms of absolute number of D2 receptors and of transducing mechanisms linked to D1 receptors. These changes suggest that the dopaminergic system may be particularly sensitive during aging to environmental, iatrogenic and toxic factors, which may easily make the elderly develop symptoms of central dopamine deficiency.

Aging↗
PubMed1988

Aging modifies the asymmetry in brain microvascular regulation.

Cerebral ischemia induced by unilateral carotid occlusion in rats decreases in an asymmetric manner the number of beta-adrenergic receptors in microvessels prepared from cerebral cortexes ipsilateral and contralateral to the side of the ligature. In particular, the reduction is more pronounced in the left hemisphere in case of both right and left carotid ligature. The greater receptor decrease in the left side of the brain was shown to depend on the integrity of interhemispheric connections. We show that the changes in capillary beta-adrenergic receptors in response to unilateral carotid occlusion are qualitatively modified during aging. In particular, the asymmetry in the response pattern observed in young rats is lost. The mechanisms underlying this phenomenon may be based on an age-related impairment in the transfer of neuronal information between the two sides of the brain.

Aging↗
PubMed1987

Alcohol impairs age-dependent adaptation of human lymphocyte beta-adrenergic receptors.

Lymphocyte beta-adrenergic receptor function and norepinephrine (NE) plasma concentration have been compared in normal subjects and in ethanol-addicted patients of different ages. Direct measurement of the density and properties of beta-adrenoceptors in membrane fractions was performed using the radioligand 125I-Iodocyanopindolol (ICYP). In normal subjects beta-receptor density decreased and norepinephrine plasma concentration increased with age. There was a statistically significant negative correlation between plasma norepinephrine and beta-receptor number. In ethanol-addicted patients the age-related modification in beta-receptor number and the correlation between plasma norepinephrine and beta-receptor density were lost, in spite of the fact that the increase of NE plasma concentration was still present. The ethanol-induced effects in lymphocyte beta-receptor may have consequences on immunological function and may be qualitatively similar to alterations in other tissues not routinely accessible in humans.

Adaptation, Physiological↗
PubMed1987

Microcirculation and neurotransmitter metabolism in the pathophysiology of brain ischaemia. A role for calcium.

Calcium is an essential component in a multitude of cellular processes, ranging from muscle contraction to cell division, and hormone and neurotransmitter release. Disruption of calcium homeostasis at the neuronal level, which occurs in pathological events such as ischaemia, causes a series of biological reactions that ultimately lead to cell death. Furthermore, calcium-triggered events may influence vascular activity, causing spasm at the level of the major vessels and inducing changes in the permeability of the blood-brain barrier. Thus, knowledge of the biochemical events involved in the initiation and progression of cell injury occurring in acute cerebrovascular events may have important implications for possible strategies of pharmacological intervention such as calcium entry blockade.

Blood-Brain Barrier↗
PubMed1986

[Vascular and neuronal mechanisms of calcium antagonists. Significance in neurological therapy].

Calcium-channel entry blockers are drugs with different chemical properties and a common pharmacological characteristic. Calcium is very important in many physiological mechanisms and could be involved in neuronal damage following cerebral ischemia. Thus, calcium-channel blockers agents could be of interest in medical treatment of cerebrovascular diseases, headache and subarachnoid hemorrhage. Calcium-channel blockers seem to have a direct protective role against neuronal ischemic damage and/or a direct action on cerebral vessels. Some clinical experiences have suggested a protective role of nimodipine in the prevention of ischemic complications related to cerebral vasospasm after subarachnoid hemorrhage.

Blood-Brain Barrier↗
PubMed1986

Partial reversal of asymmetry in microvessel neurochemical changes after ischemia by corpus callosum section.

Common carotid occlusion in the rat significantly decreases the density of beta-adrenergic receptors in preparations of microvessels obtained from ipsilateral and contralateral cerebral cortices. The disruption of nerve pathways connecting the hemispheres (callosal transection) partially reverses the effect of common carotid occlusion on beta-adrenergic receptor density in capillaries of the contralateral cortex. In addition, the destruction of the central noradrenergic system by intraventricular injection of 6-hydroxydopamine abolishes the effect of ischemia on capillary beta-adrenergic receptor function in both hemispheres. The results suggest that beta-adrenergic receptors located on microvessels are partially regulated by neuronal pathways and that focal ischemia induces neurochemical and functional changes in remote areas of the brain.

Animals↗
PubMed1985

Neuronal control of brain microvessel function.

Cerebral capillary endothelium forms a barrier limiting and controlling the movement of ions and solutes between blood and brain. Recent anatomical, physiological and biochemical studies have suggested the possibility that capillary function may be directly controlled by neuronal structures. Alterations in neuronal systems involved in the regulation of microcirculation may account for microvascular dysfunctions which occur in different pathologic conditions.

Acetylcholine↗
PubMed1985

Low activity of angiotensin-converting enzyme in cerebral microvessels of young spontaneously hypertensive rats.

Angiotensin-converting enzyme (ACE) activity was measured in microvessels prepared from cerebral cortices of 4-week-old spontaneously hypertensive rats (SHR). The Vmax value of the ACE activity in the cerebral microvessels of SHR was lower than that of Wistar Kyoto controls of the same age by 25% without difference in Km value for substrate. The low activity of ACE in the cerebral microvessels of young SHR indicates that in this animal model of hypertension the function of ACE is genetically altered in the cerebral microvessels, which may be correlated with the alteration of the cerebral microcirculation and pathogenesis of hypertension.

Animals↗
PubMed1985

alpha-Adrenergic receptors in cerebral microvessels of normotensive and spontaneously hypertensive rats.

In rat cerebral microvessels, we characterized alpha 1- and alpha 2-adrenergic receptors, using [3H]prazosin and [3H]-p-amino-clonidine as radioligands. [3H]Prazosin binding to the cerebral microvessels was saturable and of high affinity (dissociation constant of 78 pM), with a maximum binding of 48 fmol/mg protein. [3H]Prazosin binding reached equilibrium within 15 minutes and was dissociated by the addition of 10 microM phentolamine. The inhibitory effects of isomers of norepinephrine and epinephrine on the binding showed that l-isomers were over 10 times more potent than d-isomers. [3H]-p-Amino-clonidine binding to the cerebral microvessels was saturable and of high affinity (KD = 0.61 nM) with a Bmax of 73 fmol/mg protein. The binding reached equilibrium within 30 minutes, and was dissociated by the addition of 100 microM l-norepinephrine. l-Isomers of norepinephrine and epinephrine were over 10 times more potent than d-isomers in displacing the binding. Thus, both [3H]prazosin and [3H]-p-amino-clonidine bindings to the cerebral microvessels were characterized by saturability, high affinity, reversibility, and stereo-specificity. Furthermore, the specificity of both binding sites was pharmacologically evaluated by the inhibitory effects of various adrenergic agonists and antagonists on the bindings. These data indicate the existence of alpha-adrenergic receptors in the cerebral microvessels and are consistent with the hypothesis that the cerebral microcirculation is regulated by adrenergic innervation. Furthermore, the receptors were measured in cerebral microvessels of spontaneously hypertensive rats and Wistar-Kyoto controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Non-vascular central nervous system effects of calcium entry blockers.

Calcium entry blocker (CEB) use has been proposed in a variety of neurological dysfunctions. Some of the new clinical applications suggest a direct non-vascular action on neuronal activity. This view is supported by the observation that in brain CEBs bind preferentially to neuronal terminals and not to vascular elements. The data reported indicate that CEBs modify both in vitro and in vivo neurotransmitter release using brain slices and that their binding sites display some degree of plasticity in various experimental conditions altering neuronal transmission.

Age Factors↗
PubMed1984

beta-Adrenergic receptors in brain microvessels of diabetic rats.

A significant decrease in the number of beta-adrenergic receptors was observed in cerebral microvessels of fatty (fa/fa) and streptozotocin-induced diabetic rats, without receptor affinity changes. These results suggest that alterations of central adrenergic regulation of small vessels may be involved in brain microvasculature disturbances that occur with diabetes.

Animals↗
PubMed1984

Angiotensin-converting enzyme activity is reduced in brain microvessels of spontaneously hypertensive rats.

Angiotensin -converting enzyme (ACE) activity in brain microvessels of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) controls was measured. Cerebral microvessels, prepared from the cerebral cortices by the albumin flotation and glass bead filtration technique, were free of neuronal and glial elements. ACE activity in brain microvessels of SHR was lower than that of WKY. A Woolf - Augustinsson -Hofstee plot showed that the reduction of the enzyme activity in SHR was due to a 30% decrease in Vmax, without any change in Km for substrate. The decrease of ACE activity in brain microvessels of SHR may indicate an impairment of the central renin-angiotensin system and may be related to cerebral microvascular dysfunctions occurring in hypertension.

Animals↗
PubMed1984

Chronic ethanol treatment changes the number of beta-receptors in rat brain microvessels.

The effect of chronic ethanol consumption on the binding (125I)-iodohydroxybenzylpindolol to beta-adrenergic receptors in rat brain microvessels has been studied. The results show that chronic ethanol treatment increases the number of beta-receptors present in brain microvessels without changing the binding affinity of the binding site for the beta-adrenoceptor ligand. This effect is apparently not associated with changes in peripheral adrenergic tone, since no differences in platelet epinephrine or norepinephrine concentrations were found between ethanol-treated and control animals. An increase in beta-receptor density in brain microvessels might contribute to the alterations of cerebral blood flow and oxygen consumption reported during chronic ethanol intoxication.

Animals↗
PubMed1983

Hypertension reduces the number of beta-adrenergic receptors in rat brain microvessels.

Beta-adrenergic receptor function was measured in cerebral microvessels of spontaneously and DOCA-salt hypertensive rats using 125I-iodohydroxybenzylpindolol (IHYP). Both in genetic and in experimental hypertension, a significant decrease in the number of beta-receptor sites was observed, without receptor affinity changes. These results suggest that alterations of central adrenergic regulation of small vessels may participate in the pathogenetic mechanisms leading to the development of the central hypertensive disease.

Animals↗