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Biomedical subjects

M Zoli

Publications and source records attributed to M Zoli.

At least 73 records · Page 4Linked to original sources
PubMed1997

Interobserver and interequipment variability of hepatic, splenic, and renal arterial Doppler resistance indices in normal subjects and patients with cirrhosis.

BACKGROUND/AIMS: Doppler arterial resistance indices are used to evaluate alterations in arterial hemodynamics in the liver, spleen, and kidney. The purpose of this study was to determine the interobserver and interequipment variability of hepatic, splenic, and renal arterial Doppler resistance indices, and the influence of a cooperative training program of the operators on the reproducibility of the results. METHODS: In the first part of the study, hepatic (PI-L, RI-L), splenic (PI-S, RI-S), and renal (PI-K, RI-K) pulsatility and resistive indices were measured by echo-color-Doppler in eight control subjects and ten patients with cirrhosis by three operators using three different machines. In the second part of the study, measurements were taken by the three operators in nine controls and nine patients with cirrhosis, after cooperative training, with a single machine. RESULTS: Significant interobserver variability was present for all parameters except RI-L. Significant interequipment variability was present for all parameters except PI-S and RI-S. Only 0-3% of variance was equipment- or operator-related, while 58-72% was patient-related. Hepatic and renal coefficients of variation were similar in patients with cirrhosis and controls, while splenic coefficients of variation were higher in patients with cirrhosis than in controls. After training, differences among operators disappeared for all variables except RI-K, and the operator-related component of variance nearly disappeared for all parameters. CONCLUSIONS: Hepatic, splenic, and renal arterial resistance indices show small but significant interobserver and interequipment variability. Interobserver variability can be decreased to non-significant levels by a common training program. Thus, these indices can be widely applied to the study of arterial circulation in these organs.

Female↗
PubMed1997

Glutathione kinetics in normal man and in patients with liver cirrhosis.

BACKGROUND/AIMS: The dynamics of glutathione in plasma has always been studied by bolus injections. Data are available suggesting that the low plasma levels of cirrhosis are due to decreased production in glutathione-producing tissues, mainly the liver. We aimed to measure the kinetics of glutathione during controlled steady-state conditions, and to determine the reasons for its reduced plasma levels in advanced cirrhosis. METHODS: The plasma clearance of glutathione was measured in six control subjects and in ten patients with cirrhosis during a 2-step infusion study, producing steady-state levels approximately 5 and 10 times basal values. The plasma disappearance curve after infusion stop was used to determine the apparent volume of distribution and half-life of glutathione, and the estimated basal appearance rate. RESULTS: The clearance of glutathione did not reject 1st-order kinetics, i.e., it was concentration-independent, and was nearly doubled in cirrhosis. The half-life of exogenous glutathione was not different, whereas the volume of distribution was larger in cirrhosis, in the same range as extracellular water. The endogenous basal appearance rate of glutathione was reduced by 50%, and correlated with liver function, measured by routine and dynamic tests. CONCLUSIONS: The data confirm that the primary defect responsible for reduced glutathione in liver disease is a reduced production, possibly related to hepatocyte dysfunction and a block along the pathway of methionine metabolism.

Adult↗
PubMed1997

Protective effects of delapril, indapamide and their combination chronically administered to stroke-prone spontaneously hypertensive rats fed a high-sodium diet.

1. Stroke-prone spontaneously hypertensive rats (SHRsp) have been used widely to test agents putatively capable of vascular protection. These animals present an accelerated time course of hypertension and a reduced life-span. When fed a high-sodium diet from the eighth week of life, a further acceleration in blood pressure increase is obtained, and rats start to die after 5 weeks of diet as a consequence of cerebral haemorrhage. In this model, angiotensin-converting enzyme (ACE) inhibitors were repeatedly proved to prevent vascular lesions and death. Notably, this effect was independent of any hypotensive effect. On the contrary, diuretics were shown not to be equally effective. A combination of ACE inhibitors and diuretics, although known to have synergistic effects in the therapy of hypertension, has never previously been tested. 2. Our aim was to study the effects of long-term treatment with the ACE inhibitor delapril (12 mg day-1 kg-1), the thiazide-like diuretic indapamide (1 mg day-1 kg-1), and their combination (12 and 1 mg day-1 kg-1 respectively), on the survival of SHRsp rats fed a high-sodium diet from the eighth week of life onwards. The effects of the treatments on blood pressure, body weight, food and fluid intake, diuresis, proteinuria and the appearance of lesion signs and death were assessed weekly. When control rats reached 50% mortality, they were killed, together with some drug-treated rats, to compare lesions in brain and kidney. The other drug-treated rats continued treatments until 50% mortality was reached in two treatment groups. 3. All drug treatments were able to delay death significantly when compared with control rats, which reached 50% mortality after 6 weeks of salt loading. This event was preceded by a highly significant increase in proteinuria, diuresis and fluid intake that took place 3 weeks after the increase in blood pressure over the initial range. In delapril- or indapamide-treated SHRsp these changes were never seen, even when animals started to die. In the combination-treated group, a significant increase (P < 0.01) in fluid intake and diuresis, but not proteinuria, was observed from the third week of treatment onwards. 4. Treatment with delapril or indapamide did not block the progressive increase in blood pressure as observed in control animals. However, the increase in blood pressure was markedly retarded with respect to control rats. At variance with this, in combination-treated animals blood pressure levels were maintained until the end of the experiment within the 99% confidence interval initially observed in control animals. 5. Infarctual and haemorrhagic cerebral lesions were observed in 38% of control rats; no lesions were noted in brains of age-matched rats receiving a drug treatment. Kidneys from control animals presented major degenerative lesions of glomeruli and arteries, characterized by fibrinoid necrosis. This condition was absent in drug-treated animals, which presented minor signs of ischaemic lesion. Heart hypertrophy, when heart weight was expressed as a percentage of body weight, was similar in saline-, delapril- or indapamide-treated rats. At variance with this, in combination-treated animals the heart weight to body weight ratio was significantly (P < 0.01) lower than in the other groups. 6. In conclusion, the diuretic indapamide showed similar protective effects as the ACE inhibitor delapril on acute vascular lesions and survival of SHRsp. Moreover, their combination synergized in preventing heart hypertrophy consequent to longterm hypertension. This results is probably related to the enhanced diuresis and the better control of blood pressure levels selectively found in combination-treated animals.

Analysis of Variance↗
PubMed1997

Uncertainty in liver function assessment on the basis of single-point galactose concentration.

The uncertainty in liver function assessment based on single-sample galactose levels after galactose injection, in comparison to the standard procedure using the galactose elimination capacity (GEC), was assessed in 905 tests performed in a wide range of liver functions. The 45-min galactose levels significantly correlated with GEC, the correlation being better in subjects with a good liver function. In cirrhosis, the prediction using the 60-min galactose value was better than when the 45-min value was used. In the whole series, the 95% confidence interval of GEC predicted by 45-min galactose was as large as +/- 1.55mg x kg(-1) x min(-1) as absolute value, corresponding to a range from -41 to +47% of measured GEC. In cirrhosis, the 95% confidence interval was +/- 1.42 mg x kg(-1) x min(-1) and between -40 and +46% of measured GEC. The 60-min values were more predictive, but in Child class C patients the average error was 0.42 mg x kg(-1) x min(-1) (95% confidence interval -0.64 to +1.49, corresponding to -39 to +76% of measured GEC). The uncertainty was maintained within +/- 10% of measured values only in 50% of the tests. We conclude that the single-point galactose test introduces a considerable error, mainly in patients with more advanced liver disease, which may bias the decision-making process.

Analysis of Variance↗
PubMed1997

Short- and long-term changes in striatal neurons and astroglia after transient forebrain ischemia in rats.

BACKGROUND AND PURPOSE: The striatum is one of the regions most sensitive to transient forebrain ischemia. After 30-minute ischemia, areas of massive neuronal degeneration are clearly detectable a few hours after the insult and attain their maximal extension 24 hours after the insult. However, for most cellular and neurochemical parameters it is not known whether some recovery occurs at later times. We examined certain cell populations in the caudate putamen at different times after transient ischemia. METHODS: Adult male Sprague-Dawley rats were subjected to 30-minute forebrain ischemia (four-vessel occlusion model). Six experimental groups were considered: control animals and ischemic animals killed 4 hours, 1 day, 7 days, 40 days, and 8 months after reperfusion. Three striatal cell populations were examined by means of immunocytochemistry coupled to computer-assisted image analysis: vulnerable medium spiny neurons, resistant aspiny neurons, and reactive astrocytes, labeled for their content of dopamine- and cAMP-regulated phosphoprotein mr32 (DARPP-32), somatostatin and neuropeptide Y, and glial fibrillary acidic protein, respectively. RESULTS: (1) The area containing DARPP-32 immunoreactive neurons was markedly decreased (15% to 20% of control caudate putamen area) at 1 day after reperfusion and partially recovered at the following times (40% to 50% at 7 days and 50% to 60% at 40 days and 8 months after reperfusion). (2) The appearance of reactive astrocytes was precocious (4 hours to 1 day after ischemia) in the medial caudate putamen, the region in which DARPP-32 recovered within 40 days after ischemia, and late (7 to 40 days after ischemia) in the lateral caudate putamen, where no DARPP-32 recovery was detected. (3) Neuropeptide Y/somatostatin-containing neurons resisted the ischemic insult and could be detected in areas devoid of DARPP-32 immunoreactive neurons as long as 8 months after reperfusion. CONCLUSIONS: The present results show a marked recovery of DARPP-32-positive neurons within 40 days after 30-minute forebrain ischemia in the medial, but not the lateral, caudate putamen. Medial caudate putamen also contains a high density of reactive astrocytes on the first day after ischemia, suggesting that astrocytic support has an important role in the spontaneous recovery of ischemic neurons.

Animals↗
PubMed1996

Efficacy of a surveillance program for early detection of hepatocellular carcinoma.

BACKGROUND: Contrasting data have so far been reported on the utility and efficacy of screening patients with cirrhosis for early detection of hepatocellular carcinoma (HCC). The goal of this study was to evaluate the efficacy of a regular ultrasonographic and laboratory follow-up for the early detection of small HCC, and to identify parameters correlated with a higher risk of developing HCC. METHODS: One hundred and sixty-four consecutive patients with liver cirrhosis living in Emilia Romagna, Italy, were enrolled in the period 1989-1991. All patients underwent clinical, biochemical, and ultrasonographic evaluations at entry and at 3- and 6-month intervals during follow-up. RESULTS: By April 1995, 34 patients had developed HCC. In 76% of the patients, ultrasonography identified HCC when it was still single and small (< 4 cm). At discriminant, logistic regression and univariate analyses, sex and the entry concentration of alkaline phosphatase, alpha-fetoprotein, gamma-glutamyl transpeptidase, and albumin were associated with a higher risk of developing HCC, whereas at multivariate analysis (Cox's model), only sex and the entry concentration of alkaline phosphatase, albumin, and alpha-fetoprotein were independently and significantly related to the appearance of HCC. CONCLUSIONS: A regular ultrasonographic follow-up, timed at 3- to 6-month intervals according to the risk of HCC development in patients with cirrhosis, allows the detection of liver carcinoma at an early stage in a high proportion of patients, possibly improving the prognosis of the disease.

Adult↗
PubMed1996

Regional and cellular distribution of spermidine/spermine N1-acetyltransferase (SSAT) mRNA in the rat central nervous system.

Spermidine/spermine N1-acetyltransferase (SSAT) is the key enzyme responsible for polyamine interconversion. SSAT mRNA (visualized by in situ hybridization histochemistry) was shown to have a wide but heterogeneous distribution in the central nervous system (CNS) at both regional and cellular levels. The highest labelling was observed in hippocampus (pyramidal and polymorph neurons) and olfactory bulb. Present data suggest that polyamine metabolism in the CNS is not homogeneous but rather that the preferential production of a polyamine species is region- and cell type-specific.

Acetyltransferases↗
PubMed1996

Spermidine/spermine N1-acetyltransferase mRNA levels show marked and region-specific changes in the early phase after transient forebrain ischemia.

Considerable evidence points to an involvement of natural polyamines (putrescine, spermidine and spermine) in trophic regulation of brain tissue. Spermidine/spermine N1-acetyltransferase is the key enzyme in the interconversion pathway which leads to the formation of spermidine and putrescine from spermine and spermidine, respectively. In the present paper we have studied using in situ hybridization histochemistry the levels of spermidine/spermine N1-acetyltransferase mRNA in the rat central nervous system after transient forebrain ischemia. In the first hours after the insult, a modest increase in spermidine/spermine N1-acetyltransferase mRNA levels was observed in ependymal cells and other non-neuronal cells of all telencephalic and diencephalic regions. In addition, major increases in spermidine/spermine N1-acetyltransferase mRNA levels were observed in regions selectively vulnerable to the ischemic insult, such as striatum, hippocampus and cerebral cortex, during the first day post-reperfusion. The time course and extent of labelling increase were subregion- and cell-specific. At the cellular level, the labelling appeared markedly increased in neurons (8-10 fold in ventromedial striatum and CA1 region) and, to a lesser extent, in non-neuronal cells. The increase in SSAT mRNA levels was not directly related to cell degeneration, as it was detected in both some vulnerable and some resistant cell populations. However, the peak increase of SSAT labelling was precocious in resistant neurons (such as those of ventromedial striatum and dentate gyrus granular layer) and delayed or very limited in vulnerable neurons (such as those of CA1 pyramidal layer and dorsolateral striatum). The increase in spermidine/spermine N1-acetyltransferase may contribute to the increase in putrescine and decrease in spermidine levels observed after ischemia and gives further support to the notion that polyamine metabolism in the early phase after lesion is oriented towards putrescine production. This phenomenon could be relevant in determining the prevalence of neurotrophic vs. neurotoxic effects of polyamines.

Acetyltransferases↗
PubMed1996

Wiring and volume transmission in the central nervous system: the concept of closed and open synapses.

During the past two decades, several revisions of the concepts underlying interneuronal communication in the central nervous system (CNS) have been advanced. Our group has proposed to classify intercellular communication in the CNS under two general frames: 'wiring' (WT) and 'volume' transmission (VT). WT is characterized by a single 'transmission channel' made by cellular (neuronal or glial) structures and with a region of discontinuity not larger than a synaptic cleft. VT is characterized by the diffusion from a cell source (neuronal or glial) of chemical and electrical signals in the extracellular fluid (ECF) for a distance larger than the synaptic cleft Based on morphological and functional characteristics, and in light of the distinction proposed, six main modes of intercellular communication can be recognized in the CNS: gap-junction, membrane juxtaposition, and closed synapse (which represent WT-type modes of communication); open synapse, paracrine transmission and endocrine-like transmission (which represent VT-type modes of communication). Closed and open synapses are distinguished on the basis of the sealing of the signal within or the leakage of the signal outside the synapse Intra-synaptic restriction or extra-synaptic diffusion of transmitters are insured by a number of anatomical arrangements (e.g. glial ensheathment of synapse, size of the synaptic cleft) and functional mechanisms (e.g. density and location of transmitter re-uptake sites and metabolic enzymes). Some central synapses can switch from closed to open state and vice versa, e.g. by changing the amount of transmitter released. Finally, a synapse containing several transmitters can work as an open synapse for one transmitter and as a closed synapse for another.

Animals↗
PubMed1996

Computer-assisted mapping of basic fibroblast growth factor immunoreactive nerve cell populations in the rat brain.

We have performed a mapping of basic fibroblast growth factor (bFGF) immunoreactive (ir) glial and nerve cell populations in the male rat brain using a rabbit antibody raised against a synthetic peptide of bovine bFGF. Regional morphometric and microdensitometric analysis of the bFGF ir neuronal profiles in coronal brain sections was carried out by means of an automatic image analyser. The density and intensity of the bFGF ir glial profiles were subjectively evaluated. The bFGF immunoreactivity (IR) was detected within the cytoplasm of neurons, except within the pyramidal neurons of hippocampal CA2 region, the fasciola cinerea and the indusium griseum, where bFGF IR was present in the nucleus. In contrast, in glial cells bFGF IR was always found in the nucleus. Neuronal and glial IR was no longer observed after absorption of the bFGF antiserum with recombinant bFGF. Basic FGF IR was found in neuronal and glial cell populations throughout the brain as well as in the choroid plexus and in the ependymal cells lining the ventricles. Basic FGF ir nerve cells were found in all layers of both the neocortex and allocortex. Within the caudate putamen and the nucleus accumbens a low density of weak bFGF ir neuronal profiles was detected. The majority of the thalamic nuclei showed medium to high densities of moderate to strong bFGF ir neuronal profiles. All the hypothalamic nuclei, with the exception of the anterior and lateral hypothalamic area and of the ventral hypothalamic nucleus, contained a high density of bFGF ir profiles. The pons and the medulla oblongata were characterized by the presence of a large number of nuclei containing moderate to high densities of strong bFGF ir profiles. The Purkinje cell layer of the cerebellar cortex contained a high density of moderately bFGF ir profiles. A moderate density of strong bFGF ir nerve cell profiles was observed within all the laminae of the spinal cord, except within the II and III laminae where a high density of strongly ir profiles was found. Histogram analysis of total immunoreactivity showed that the distribution of bFGF ir profiles within the telencephalon and mesencephalon tend to be similar with regard to the central tendency and spread. Using Kendall's tau, a significant correlation between intensity and density values was obtained only in the diencephalon. The cytoplasmic bFGF IR found in distinct nerve cell populations all over the rat brain and spinal cord may represent forms of bFGF which can be released from the nerve cells via non-exocytotic mechanisms in view of the absence of an intracellular signal peptide in bFGF. The presence of nuclear bFGF IR within the glial cells all over the central nervous system (CNS) suggests an intracellular function of bFGF, such as the promotion of mitogenesis and/or participation in the transcriptional regulation of various genes.

Animals↗
PubMed1996

Transdermal nitroglycerin in cirrhosis. A 24-hour echo-Doppler study of splanchnic hemodynamics.

BACKGROUND/AIMS: The present study was aimed to evaluate the 24-hour effect of transdermal nitroglycerin on splanchnic hemodynamics in cirrhotic patients. METHODS: Hemodynamic parameters (blood velocity and resistance indexes) were determined by means of pulsed echo-Doppler, a non-invasive method which proved to be useful to evaluate the effects of drugs on splanchnic vessels. Nine patients with biopsy-proven liver cirrhosis were studied. They were kept on a standard diet divided into 3 meals served at 8, 12 a.m. and 6 p.m. Echo-Doppler measurements were determined for 2 consecutive days at 7, 8, 9, 12 a.m, 1, 3, 6, 7, 9, 12 p.m. and again at 7 a.m. A transdermal nitroglycerin tape, capable of releasing 15 mg of the drug in 24 h, was applied to the skin of the chest at 7 a.m. of the second day. RESULTS: After nitroglycerin mean portal blood velocity and flow significantly decreased by 18 and 22%. Similarly superior mesenteric artery velocity decreased, while resistance indexes increased. ANOVA analysis showed a significant effect of the drug on superior mesenteric artery and portal flow, while the effect on hepatic artery flow and renal indexes were low. CONCLUSIONS: This study shows that nitroglycerin, given as transdermal long-acting system, significantly influences portal hemodynamics in liver cirrhosis. Its use, favoured by easy administration, may be proposed for long-term clinical studies to test its efficacy in preventing gastrointestinal bleeding.

Administration, Cutaneous↗
PubMed1996

Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis.

Zinc deficiency is common in cirrhosis and has been involved in the altered nitrogen metabolism. In this study, we measured the effects of zinc supplementation on the dynamics of amino acid-derived urea synthesis in cirrhosis with mild or latent encephalopathy. The hepatic conversion of amino acids into urea was studied in eight patients with advanced cirrhosis under controlled conditions of substrate availability (continuous alanine infusion), before and after 3-month oral zinc sulfate supplementation (600 mg/d). Eight more patients, matched for hepatocellular failure and encephalopathy, served as controls. Plasma zinc levels were reduced in all patients and returned to normal after oral zinc. The alanine-stimulated urea nitrogen synthesis rate in relation to alpha-amino-N concentration--the functional hepatic nitrogen clearance--increased by 25% after zinc supplementation, i.e., more urea was produced at any alpha-amino-N concentration. Basal and alanine-induced glucagon decreased by 50%, and the ammonia response to alanine decreased by 30%. Psychometric tests improved, as did routine and dynamic liver function tests and the Child-Pugh score. Also, the plasma concentration of lipid peroxides was reduced by zinc. No significant changes were observed in the control group. Our data indicate that long-term oral zinc speeds up the kinetics of urea formation from amino acids and ammonia. Changes in the hormonal drive and/or the antioxidant activity of zinc might be involved in the general improvement in liver function, whereas the beneficial effects on encephalopathy might stem from decreased ammonia.

Administration, Oral↗
PubMed1996

The course of galactose elimination capacity in patients with alcoholic cirrhosis: possible use as a surrogate marker for death.

There is increasing interest for the use of surrogate end points in the evaluation of treatments in patients with liver disease, but adequate validation is seldom available. This study aimed to describe the different course of galactose elimination capacity in patients with alcoholic cirrhosis who continued to drink or abstained from alcohol consumption during follow-up, and to validate changes in galactose elimination as a surrogate end point for death from liver-related causes. Forty-five patients with alcoholic cirrhosis (22 who continued drinking throughout the study period, and 23 who stopped drinking and were abstinent throughout the study period) were retrospectively selected among patients who had galactose elimination capacity measured at 6-month intervals. During follow-up 10 drinkers and 3 abstainers died of liver-related causes (P = .025). Abstainers showed a transient improvement in galactose elimination capacity, followed by a decrease. Continuous drinkers showed a reduction from the beginning. According to Cox's regression analyses, persistent alcohol abuse and galactose elimination capacity were separately related to the risk of death, but, when a time-dependent model was fitted containing galactose elimination capacity and persistent alcohol abuse, only the former remained significant. This implies that variations in the risk of death occurring as a consequence of abstinence from alcohol consumption may be predicted from changes in galactose elimination capacity, and that the mechanisms through which abstinence influences survival are strictly linked to the mechanisms responsible for the changes in the test. Because of the strict association of decrease in galactose elimination capacity and short survival, as proved in several series, this observation represents adherence to the criteria requested for adequacy of a surrogate end point. In conclusion, in alcoholic cirrhosis the decrease in galactose elimination capacity is an adequate surrogate end point for death from liver-related causes, which is worth testing in other conditions and in response to other treatments.

Alcoholism↗
PubMed1996

Evaluation of a new endoscopic index to predict first bleeding from the upper gastrointestinal tract in patients with cirrhosis.

The aim of this study was to prospectively evaluate the usefulness of the Italian Liver Cirrhosis Project (ILCP) classification of esophageal varices, together with the gastric features of portal hypertension, in predicting the first upper gastrointestinal bleeding in cirrhosis. The efficiency of these endoscopic parameters in predicting bleeding was also compared with the efficiency of the North Italian Endoscopic Club (NIEC) index. Three hundred forty-four cirrhotic patients with esophageal varices but without any previous bleeding were enrolled in the study. The following endoscopic parameters of esophageal varices were recorded: location, size, occupancy, blue tone, and red color signs. Gastric varices were graded as absent or present, while congestive gastropathy was considered as absent, mild to moderate, or severe. All patients were followed until the first upper gastrointestinal bleeding and/or death, or for at least 24 months. No patient received any treatment to prevent bleeding. Sixty-five patients bled from the upper gastrointestinal tract during the study. Univariate analysis showed that all endoscopic parameters were predictors of bleeding. According to multivariate analysis (Cox's model), size, gastric varices and congestive gastropathy were the only independent predictors of bleeding, and the following prognostic index (PI) was developed: PI = (size x 0.0395) + (congestive gastropathy x 0.878) + (gastric varices x 0.705). This index, which was validated using a split-sample technique, and which appears to be superior to the NIEC index in predicting bleeding, may be useful in decision making for primary prophylaxis.

Adult↗
PubMed1996

Neuronal nicotinic receptor alpha 6 subunit mRNA is selectively concentrated in catecholaminergic nuclei of the rat brain.

Although the neuronal nicotinic receptor alpha 6 subunit was cloned several years ago, its functional significance remains to be investigated. Here we describe an in situ hybridization study of the mRNA for this subunit in the adult rat central nervous system using oligonucleotide probes. Specific alpha 6 mRNA labelling was restricted to a few nuclei throughout the brain; it was particularly high in several catecholaminergic nuclei [the locus coeruleus (A6), the ventral tegmental area (A10) and the substantia nigra (A9)] at levels significantly higher than those found for any other known nicotinic receptor subunit mRNA. Labelling for alpha 6 mRNA was also detected at lower levels in the reticular thalamic nucleus, the supramammillary nucleus and the mesencephalic V nucleus. Some cells of the medial habenula (medioventral part) and of the interpeduncular nucleus (central and lateral parts) were also labelled. The distribution of alpha 6 mRNA was compared with the distribution of the other known nicotinic acetylcholine receptor subunit mRNAs. In several nuclei, the expression of alpha 6 was complementary to those of other alpha subunits. Moreover, some of the cell groups (such as the substantia nigra, the ventral tegmental area and the locus coeruleus) previously thought to contain mainly alpha 3 mRNA in fact were found to contain high levels of alpha 6 mRNA. Finally, we found extensive colocalization of alpha 6 and beta 3, indicating the possible existence of nicotinic receptor hetero-oligomers containing both subunits. The present results show that alpha 6 is the major nicotinic acetylcholine receptor alpha subunit expressed in dopaminergic cell groups of the mesencephalon and noradrenergic cells of the locus coeruleus. This suggests the involvement of the alpha 6 subunit in some of the major functions of central nicotinic circuits, including the modulation of locomotor behaviour and reward.

Animals↗
PubMed1996

The receptor mosaic hypothesis of the engram: possible relevance of Boolean network modeling.

In the past 15 years, several lines of evidence have shown that receptors for chemical signals can interact in domains of the plasma membrane and possibly form molecular circuits encoding logical operators. In this frame, the receptor mosaic hypothesis of the engram was advanced. According to this proposal, aggregates of different receptor species (mosaics) may form in neuronal membranes (typically synapses) and constitute a memory trace (engram) of its activity. In the present paper, we present an attempt to model the functioning of aggregates of interacting receptors in membrane domains by means of random Boolean networks.

Animals↗