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M Zoli

Publications and source records attributed to M Zoli.

At least 91 records · Page 5Linked to original sources
PubMed1996

Characterization of the hypothalamo-pituitary-IGF-I axis in rats made obese by overfeeding.

Obesity is coupled to several disturbances of the endocrine axes. It has previously been shown that genetically obese Zucker male rats have an impaired secretion of growth hormone (GH), probably originating from a primary reduction of hypothalamic GH-releasing hormone (GHRH) function and resulting in a decrease of GH gene expression and release. We sought to evaluate the somatotropic function in another model of experimental obesity. Normal male Sprague-Dawley rats were fed an energy-rich highly palatable diet for 7 months until they reached body weights overlapping those reported for obese Zucker rats. They were then evaluated for different indices of the hypothalamo-pituitary-somatomedin-C (IGF-I) axis. At the end of the overfeeding period, rats were divided into overtly obese (obese group) and overweight (overweight group) rats according to the degree of overweight and the Obesity Lee Index, while rats fed ad libitum with the standard pellet chow served as controls. Acute administration of a supramaximal dose of GHRH (2 micrograms/rat i.v.) elicited a significantly (at least P < 0.05) lower plasma GH rise in the overweight and obese groups compared with the controls although no difference was seen in the pituitary GH content and gene expression and plasma concentrations of free IGF-I in the two experimental groups vs the controls. In addition, evaluation of hypothalamic GHRH and somatostatin mRNAs (slot-blot hybridization) did not show any significant differences between the three groups. Of the different metabolic indices investigated, plasma glucose and insulin concentrations were significantly (P < 0.01) higher in the obese than in the overweight and control groups. A sharp decrease in plasma testosterone levels, together with a reduction in testis weight, was seen in both groups of rats fed the palatable diet compared with the controls. These findings underline the 'peripheral' feature of the hyposomatotropinism of rats chronically fed an energy-rich diet, and may account for the reversibility of the GH impairment in many obese subjects once a normal body weight has been restored. Moreover, the peripherally-driven hyposomatotropinism of these rats is in sharp contrast with the hypothalamic-driven GH secretory impairment of the obese Zucker rats.

Animals↗
PubMed1996

Interobserver and inter-equipment variability of echo-Doppler sonographic evaluation of the superior mesenteric artery.

The aim of this study was to assess the interobserver and inter-equipment variabilities of echo-Doppler sonographic measurement of superior mesenteric artery flow parameters. In the first part of the study the echo-Doppler sonographic parameters (maximum systolic velocity, minimum diastolic velocity, mean velocity, restrictive index, and pulsatility index) were measured independently in nine patients by four skilled operators using four different equipment models. In the second part of the study measurements were taken by the four operators in seven different patients, after one day of cooperative training; the purpose of this part was to define a strict and uniform protocol of Doppler sonographic examination. Significantly different values of maximum systolic velocity, minimum diastolic velocity, mean velocity, and pulsatility index were obtained by the different operators, whereas the inter-equipment variability was significant only for maximum systolic velocity, mean velocity, and pulsatility index. The analysis of the components of variance showed that a large part of this variance was nonsystematic. After training and definition of the protocol no significant differences were found among the operators for any of the parameters, and the 95% confidence limits and coefficients of variation showed a decrease as for maximum systolic velocity, mean velocity, and pulsatility index. This study demonstrates that a significant systematic variability exists among mesenteric Doppler measurements obtained by different operators using different commercially available equipment. Cooperative training can reduce the interobserver variability significantly and bring to an acceptable level the reproducibility of Doppler measurements of superior mesenteric artery flow parameters.

Analysis of Variance↗
PubMed1996

Effects of single and short-term administration of clonidine on hypothalamic-pituitary somatotropic function of the adult male rat: an in situ hybridization study.

The effects of the alpha-2 adrenoceptor agonist clonidine (CLO) on the growth hormone (GH) regulatory neuronal systems, growth hormone-releasing hormone (GHRH) and somatostatin (SS), were studied in adult male rats given a single or a short-term administration (1, 3 and 6 days) of the drug. Acute administration of CLO significantly decreased hypothalamic GHRH content [leaving unaltered GHRH messenger RNA (mRNA) levels] and increased plasma GH levels; hypothalamic SS content/mRNA levels and pituitary GH content/mRNA levels remained unchanged. In 1- and 3-day CLO-treated rats, by contrast, decreased hypothalamic GHRH content was coupled with a significant reduction in GHRH mRNA levels. In these rats, pituitary GH content and mRNA levels were also significantly increased, whereas hypothalamic SS content and mRNA levels remained unaltered. In 6-day CLO-treated rats, hypothalamic GHRH content and mRNA levels were still significantly reduced, plasma GH levels were increased, but to a lesser extent than in 1- and 3-day CLO-treated rats, and pituitary GH content and mRNA reverted to control levels. Hypothalamic SS content and mRNA levels remained unaltered. These results indicate that 1) functional activation of alpha-2 adrenergic receptors by CLO increases GHRH release from the hypothalamus, 2) CLO, via GHRH, increases GH secretion and biosynthesis, which in turn feeds back in the hypothalamus to reduce GHRH biosynthesis, and 3) reduction of hypothalamic GH-stimulatory activity tones down the initial pituitary somatotropic hyperfunction. Unaltered hypothalamic SS content and mRNA levels in all CLO-treated rats suggests that the somatostatinergic system is less sensitive than the GHRH system to changes in circulating GH levels.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1996

The galactose elimination capacity test: a study of the technique based on the analysis of 868 measurements.

OBJECTIVES: Our objective in this study was to analyze the correspondence of galactose concentration-on-time-decay curve to theoretical assumptions and the confidence limits of the determination of galactose elimination capacity. METHODS: We analyzed a retrospective series of 868 galactose elimination tests, performed on subjects with and without liver disease. Zero-order kinetics of galactose elimination was tested by comparison of the residual variance of linear regression with that obtained after quadratic transformation. The uncertainty in determination of galactose elimination capacity was calculated on the regression line by computing the 95% confidence limits of the estimate. RESULTS: The time-course of galactose concentration suggested an initial uneven distribution, and the first (20-min) data point deviated significantly from the regression. The galactose decay curve in plasma rejected linearity in 13% of tests; after exclusion of the first data-point, linearity was rejected in only 3% of cases. The 95% confidence interval of galactose elimination capacity was on average +/- 16%, but in individual tests it was as large as +/- 60-80%. The uncertainty of the test was not affected by linearity. It was larger, with poor fitting of the experimental data on the regression of galactose concentration on time, low number of data points, and low galactose elimination. It was maintained within +/- 20% only when residual variance was > or = 2% of total variance (nearly 50% of tests). CONCLUSION: The methodology for the determination of galactose elimination capacity leads to considerable uncertainty as to the final result, which must be considered whenever the test is used for clinical purposes in the decision-making process. It tends to be larger in patients with advanced disease and can be accurately calculated so as to contribute to a proper evaluation of the test result.

Adolescent↗
PubMed1995

Long distance pathways of diffusion for dextran along fibre bundles in brain. Relevance for volume transmission.

Texas Red-labelled dextran with a mol. wt of 3000 g mol-1, a marker for the extracellular space, was injected unilaterally into the neostriatum of adult rats (0.3-30 micrograms microliter-1) and its distribution evaluated 1 min to 5 h later. Diffusion in the neuropil was observed with clearance starting after 30 min. After 10-15 min strong labelling along the myelinated fibre bundles was observed in the entire neostriatum. After about 20 min the labelling along the fibres reached into the corpus callosum and the overlaying deep layers of the cerebral cortex. A marked cellular uptake and accumulation of labelled dextran was found in putative perivascular pericytes. Thus, in the living brain preferential extracellular fluid pathways for diffusion exist, especially along fibre bundles, which allow the exchange of chemical signals between two distant regions. These may represent extracellular fluid pathways for volume transmission.

Animals↗
PubMed1995

A single (-)-nicotine injection causes change with a time delay in the affinity of striatal D2 receptors for antagonist, but not for agonist, nor in the D2 receptor mRNA levels in the rat substantia nigra.

The in vitro and in vivo effects of (-)-nicotine on dopamine D2 receptors in the rat neostriatum have been studied using biochemical binding, in situ hybridization and immunocytochemistry. A single i.p. injection (1 mg/kg) of (-)-nicotine resulted in a reduction of the KD value of the D2 antagonist [3H]raclopride binding sites in rat neostriatal membrane preparations at 12 h without any significant change in the Bmax value. This action of (-)-nicotine was counteracted by pretreatment 15 min earlier with the nicotine antagonist mecamylamine (1 mg/kg, i.p.). However, the KD and the Bmax values of the D2 agonist [3H]NPA binding sites in the rat neostriatal membrane preparations were not significantly affected 0.5-48 h after a single i.p. injection with 1 mg/kg of (-)-nicotine. No significant change in neostriatal D2 receptor mRNA levels was observed at any time interval after the (-)-nicotine injection. No significant change was observed in tyrosine hydroxylase (TH) immunoreactivity in either the substantia nigra or the neostriatum, nor in nigral TH mRNA levels during the time interval studied (4-24 h posttreatment). Furthermore, addition of low (10 nM) or high (1 microM) concentrations of (-)-nicotine in vitro to rat neostriatal membranes did not alter the characteristics of [3H]raclopride or [3H]NPA binding. These results indicate that a single (-)-nicotine injection can produce a selective and delayed increase in the affinity of D2 receptors for the antagonist, but not for the agonist without modifying the levels of D2 receptor mRNA, probably via the activation of central nicotinic receptors.

Animals↗
PubMed1995

Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain.

Nicotine affects many aspects of behaviour including learning and memory through its interaction with neuronal nicotinic acetylcholine receptors (nAChR). Functional nAChRs are pentameric proteins containing at least one type of alpha-subunit and one type of beta-subunit. The involvement of a particular neuronal nicotinic subunit in pharmacology and behaviour was examined using gene targeting to mutate beta 2, the most widely expressed nAChR subunit in the central nervous system. We report here that high-affinity binding sites for nicotine are absent from the brains of mice homozygous for the beta 2-subunit mutation. Further, electrophysiological recording from brain slices reveals that thalamic neurons from these mice do not respond to nicotine application. Finally, behavioural tests demonstrate that nicotine no longer augments the performance of beta 2-1- mice on passive avoidance, a test of associative memory. Paradoxically, mutant mice are able to perform better than their non-mutant siblings on this task.

Animals↗
PubMed1995

Interobserver and interequipment variability of echo-Doppler examination of the portal vein: effect of a cooperative training program.

The aim of this study was to assess the interobserver, interequipment, and time-dependent variabilities of echo-Doppler measurements of portal blood flow velocity (PBV), portal vein diameters (PVDs) and their derived parameters, portal blood flow (PBF), and congestion index (CI) in cirrhotic patients. The influence of a cooperative training program of the operators on the reproductibility of the results was also investigated. The echo-Doppler parameters were independently measured in 15 patients by four skilled operators, using four echo-Doppler machines (Acuson, ATL, Hitachi-Esaote, Toshiba. Eight of the 15 patients were restudied after 15 days by the same operators using only one machine. Significantly different values of PBV, PBF, and CI were obtained. PBV variance was equipment-related (32%) and operator-related in a smaller portion (5%). No systematic effect related to the time of investigation was found. After training to define a precise protocol, new measurements were performed by four operators on 8 different patients. No significant differences were found among the operators for any of the parameters and the 95% confidence limits (CL) and coefficients of variation (CV) of PBV showed a marked decrease (CL from +/- 26.4% to +/- 15.6%). These results indicate that (1) a significant systematic variability exists between Doppler measurements with different equipment; (2) there is no significant time-dependent systematic variability of Doppler measurements; and (3) a cooperative training program reduces the interobserver variability for direct measurements, such as PBV.

Analysis of Variance↗
PubMed1995

Immunochemical localization of calcium/calmodulin-dependent protein kinase I.

Ca2+/calmodulin-dependent protein kinase I (CaM kinase I) was originally identified in rat brain based on its ability to phosphorylate site 1 of synapsin I. Recently a cDNA for the rat brain enzyme has been cloned and the primary structure elucidated [Picciotto et al. (1993), J. Biol. Chem., 268:26512-26521]. The rat cDNA encoded a protein of 374 amino acids with a calculated M(r) of 41,636. Antibodies have now been raised against the recombinant kinase expressed in E. coli as a glutathione-S-transferase fusion protein. Immunoblot analysis of rat cortex lysates revealed two major immunoreactive bands of approximately M(r) 38,000 and 42,000. Minor immunoreactive species of slightly lower M(r) were also detected. Two distinct CaM kinase I activities were partially purified from rat brain and shown to correspond to the two major immunoreactive species. A variety of immunoreactive species of M(r) 35-43,000 were detected in "brain" tissue from cow, zebra finch, goldfish, Xenopus, lamprey, and Drosophila. In rat brain, immunocytochemistry revealed strong staining in cortex, hippocampus, amygdala, hypothalamus, brain stem, and choroid plexus. The labelling was mainly observed in neuropil but clusters of intensely labelled neuronal cell bodies were also detected all along the neuraxis. Neuronal nuclei and glial cells did not appear to be stained. Subcellular fractionation studies confirmed the cytosolic localization of the kinase in the brain. In various rat non-neuronal tissues and in a number of cell lines, immunoreactive species of approximately M(r) 38,000 and approximately 42,000 were detected at lower levels than that detected in brain. The M(r) 38,000 and 42,000 species were also found in different ratios and at different levels in the non-neuronal tissues. These results support a role for CaM kinase I in the regulation of multiple neuronal processes. Furthermore, the widespread cell and tissue distribution suggests that CaM kinase I may function as a ubiquitous multi-functional protein kinase. Finally, the multiple immunoreactive species may represent isoforms of CaM kinase I.

Animals↗
PubMed1995

Thyroid volume in type 1 diabetes patients without overt thyroid disease.

An association between insulin-dependent diabetes mellitus (type 1) and thyroid diseases has long been reported, but the morphological evaluation of the thyroid in type 1 diabetes patients without overt thyroid disease has always been limited to physical examination. Ultrasonography of the thyroid gland was performed in 45 patients with type 1 diabetes without overt thyroid disease, to study thyroid volume and the prevalence of thyroid nodules. Data were compared with those obtained in 45 age- and sex-matched control subjects residing in the same area. In the patients, thyroid volume had increased on average by 46%; 35% of male and 32% of female patients had a thyroid volume exceeding the 95% confidence limits of the matched controls. The prevalence of thyroid nodules was only slightly raised. On average, free thyroxine was increased in the presence of normal triiodothyronine levels. Four patients were frankly hyperthyroid. The patients also showed a higher prevalence of thyroid-microsomal antibodies, but the thyroid hormone status was not different in relation to thyroid volume, nor was thyroid volume in relation to the presence of autoantibodies. Patients with type 1 diabetes without overt thyroid disorders may have morphological, ultrasonographically detectable alterations of the thyroid gland, the expression of a possible involvement of the thyroid in an autoimmune disorder not limited to the islet cells.

Adolescent↗
PubMed1995

Effects of beta-blockade on hepatic conversion of amino acid nitrogen and on urea synthesis in cirrhosis.

beta-Blockers are widely used to prevent gastrointestinal hemorrhage in cirrhosis. The metabolic effects of treatment are scarcely studied: hepatic function reportedly does not change significantly, but beta-adrenoceptors have been reported to regulate protein and amino acid metabolism. We studied hepatic nitrogen metabolism in response to constant alanine infusion in seven patients with cirrhosis before and 7 to 10 days after treatment with oral propranolol (60 to 100 mg/d). Beta-blockade was effective: it decreased heart rate by 25%, abolished orthostatic tachycardia, and reduced portal blood flow by 20%. Alanine-stimulated urea nitrogen synthesis rate (UNSR) was higher in patients with propranolol treatment, without any difference in aminonitrogen concentration. The kinetics of hepatic conversion of amino acid nitrogen into urea--ie, functional hepatic nitrogen clearance (FHNC)--increased by 30%, from (mean +/- SD) 17.0 +/- 4.1 to 22.0 +/- 6.6 L/h (P < .01). Increased urea production during alanine infusion resulted in negative nitrogen exchange even at the peak of alpha-aminonitrogen concentration. Basal insulin level was only slightly reduced during propranolol treatment, whereas the insulin response to alanine was significantly blunted. No differences in glucagon and cortisol were demonstrated. Epinephrine and norepinephrine levels were high-normal and did not vary after treatment. Increased urea production and stimulation of hepatic nitrogen clearance during beta-blockade may be mediated by relative hypoinsulinemia or by direct involvement of beta-adrenoceptors in the control of nitrogen metabolism, possibly by regulation of amino acid uptake and release in peripheral tissues.

Aged↗
PubMed1995

Functional hepatic flow and Doppler-assessed total hepatic flow in control subjects and in patients with cirrhosis.

Functional hepatic flow and total hepatic flow were determined by non-invasive techniques in 32 patients with cirrhosis and in 32 paired control subjects. Functional hepatic flow was measured by the hepatic clearance of D-sorbitol, while total hepatic flow was determined by pulsed echo-Doppler, as the sum of portal and hepatic arterial blood flow. Functional hepatic flow was significantly reduced in patients with cirrhosis (927 +/- 314 vs. 1287 +/- 315; p < 0.0001), while total hepatic flow was slightly increased (1511 +/- 540 vs. 1261 +/- 321 in controls; p = 0.028). In control subjects functional hepatic flow significantly correlated with total hepatic flow (r = 0.823; p < 0.001), while no correlation was observed in cirrhosis. Functional hepatic flow and the difference between total hepatic flow and functional hepatic flow significantly correlated with the Child-Pugh score in patients with cirrhosis. The data obtained in control subjects support the measurement of functional hepatic flow and total hepatic flow by non-invasive techniques. The finding that in cirrhosis functional hepatic flow is significantly decreased, while Doppler-assessed total hepatic flow is preserved or even increased, confirms that a relevant part of blood flowing through the liver is diverted by intrahepatic shunts. The simultaneous assessment of these two parameters by non-invasive techniques may be proposed as a reliable tool for the study of functional shunting of cirrhosis.

Adult↗
PubMed1995

Promoter elements conferring neuron-specific expression of the beta 2-subunit of the neuronal nicotinic acetylcholine receptor studied in vitro and in transgenic mice.

Several genes encoding subunits of the neuronal nicotinic acetylcholine receptors have been cloned and regulatory elements involved in the transcription of the alpha 2 and alpha 7-subunit genes have been described. Yet, the detailed mechanisms governing the neuron-specific transcription and the spatio-temporal expression pattern of these genes remain largely uninvestigated. The beta 2-subunit is the most widely expressed neuronal nicotinic receptor subunit in the nervous system. We have studied the structural and regulatory properties of the 5' sequence of this gene. A fragment of 1163 bp of upstream sequence is sufficient to drive the cell-specific transcription of a reporter gene in both transient transfection assays and in transgenic mice. Deletion analysis and site-directed mutagenesis of this promoter reveal two negative elements and one positive element. The positively-acting sequence includes one functional E-box. One of the repressor elements is located in the transcribed region and is the NRSE/RE1 sequence already described in promoters of neuronal genes. In this paper, we describe the neuron-specific promoter of the gene encoding the neuronal nicotinic acetylcholine receptor beta 2-subunit.

Animals↗
PubMed1995

Intercellular communication in the brain: wiring versus volume transmission.

During the past two decades several revisions of the concepts underlying interneuronal communication in the central nervous system have been advanced. We propose here to classify communicational phenomena between cells of the central neural tissue under two general frames: "wiring" and "volume" transmission. "Wiring" transmission is defined as intercellular communication occurring through a well-defined connecting structure. Thus, wiring transmission is characterized by the presence of physically identifiable communication channels within the neuronal and/or glial cell network. It includes synaptic transmission but also other types of intercellular communication through a connecting structure (e.g., gap junctions). "Volume" transmission is characterized by signal diffusion in a three-dimensional fashion within the brain extracellular fluid. Thus, multiple, structurally often not well characterized extracellular pathways connect intercommunicating cells. Volume transmission includes short- (but larger than synaptic cleft, i.e. about 20 nm) and long-distance diffusion of signals through the extracellular and cerebrospinal fluid. It must be underlined that the definitions of wiring and volume transmission focus on the modality of transmission and are neutral with respect to the source and target of the transmission, as well as type of informational substance transmitted. Therefore, any cell present in the neural tissue (neurons, astroglia, microglia, ependyma, tanycytes, etc.) can be a source or a target of wiring and volume transmission. In this paper we discuss the basic definitions and some distinctive characteristics of the two types of transmission. In addition, we review the evidence for different types of intercellular communication besides synaptic transmission in the central nervous system during phylogeny, and in vertebrates in physiological and pathological conditions.

Animals↗
PubMed1995

Temporal changes in sulphated glycoprotein-2 (clusterin) and ornithine decarboxylase mRNA levels in the rat testis after ethane-dimethane sulphonate-induced degeneration of Leydig cells.

Short- (3-24 h) and long-term (4-50 days) changes in sulphated glycoprotein-2 (SGP-2) and ornithine decarboxylase (ODC) mRNA levels in the adult rat testis were studied following a single dose of ethane-dimethane sulphonate (EDS), to destroy the Leydig cells. Distribution patterns of SGP-2 and ODC labelling were consistent with prevailing expression of the two transcripts in Sertoli cells and germ cells, respectively. This pattern did not show appreciable changes following EDS administration. No labelling of SGP-2 mRNA was noted in the interstitium of control and EDS-treated rats. This finding indicates that Leydig cell death induced by EDS is not associated with increased SGP-2 mRNA levels, a phenomenon related to apoptotic cell death in many tissues. Semi-quantitative densitometric analysis of the preparations demonstrated differential changes in SGP-2 and ODC mRNA levels in the tubular compartment following EDS treatment. At 6, but not at 3 and 12, h following EDS administration, SGP-2 mRNA levels showed a significant increase, possibly secondary to a direct effect of the alkylating agent on Sertoli cells. A significant decrease in ODC mRNA levels was observed from day 7 to day 28, matching degenerative changes in the seminiferous epithelium. In contrast, a decrease in SGP-2 transcript levels was observed from days 21-35 after treatment. In conclusion, our findings demonstrate that SGP-2 mRNA, a putative marker of apoptosis, is not altered in the testicular interstitium during EDS-induced degeneration of Leydig cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Physical examination of the liver: is it still worth it?

OBJECTIVES: The aim of this study was to evaluate the actual role of physical examination of the liver in normal subjects and in cirrhotic patients. METHODS: One hundred healthy subjects and 100 patients with liver cirrhosis underwent a physical and an ultrasonographic evaluation of the liver by independent operators. Physical examination was performed by means of percussion and palpation to determine total liver span, liver span below the costal margin, and liver consistency. Total liver span, liver span below the costal margin, and liver volume were also determined by means of ultrasonography. RESULTS: The agreement between physical and ultrasonographic assessment of the liver span below the costal margin was poor in controls (chance corrected agreement index = 0.13) and excellent in patients (chance corrected agreement index = 0.93). Physical and ultrasonographic total liver span were correlated in patients with cirrhosis (r = 0.592) but not in controls (r = 0.205). Echo-measured liver span significantly correlated with the actual volume of the organ in both groups, whereas physical liver span significantly correlated with liver volume in cirrhosis but not in controls. The difference between actual liver volume and the value predicted by liver span was large. The cirrhotic liver was slightly reduced in size in comparison with that of healthy subjects and differed by an increase in consistency and a thickened edge. CONCLUSIONS: The bedside examination of the liver does not provide any accurate information regarding the actual volume of the organ. Its major role remains to define the characteristics of lower edge, mainly consistency, which may help in clinical diagnosis. Liver volume proved to predict prognosis in patients with cirrhosis, but its measurement needs quantitative, reproducible methods, which can be obtained only by imaging techniques.

Case-Control Studies↗
PubMed1995

Developmental regulation of nicotinic ACh receptor subunit mRNAs in the rat central and peripheral nervous systems.

In the present study we have investigated the anatomical distribution pattern of nAChR alpha 3, alpha 4, beta 2, and beta 4 subunit mRNAs during prenatal and perinatal development of the rat CNS and PNS. Three main developmental patterns have been recognized. (1) In the majority of cases studied (caudal brain, spinal cord, dorsal root ganglia, trigeminal and geniculate ganglia) all four subunit mRNAs are initially (E11-13) detected but, during subsequent prenatal development, the level of some of these subunit mRNAs (alpha 3 and beta 4 in the brain and spinal cord, alpha 4 and beta 4 in the dorsal root ganglia, alpha 4 in the visceral sensory ganglia, and alpha 3, alpha 4, and beta 4 in the somatic sensory ganglia) become undetectable. (2) In the case of the cerebral cortex a pair of subunit mRNAs (alpha 3-beta 2) is initially (E12-13) expressed followed by a repression of the alpha 3 subunit (E15) and the subsequent (E17-19) induction of the alpha 4 subunit. (3) Only some subunit mRNAs are initially (E13-15) expressed in the retina (alpha 3-alpha 4-beta 2-beta 4), parasympathetic or sympathetic motor ganglia (alpha 3-beta 2-beta 4), and vestibulo-cochlear ganglia (alpha 4-beta 2) and their level remains stable throughout prenatal and early postnatal development. Overall, in most central and peripheral structures the appearance of nAChR subunit mRNAs is precocious and temporally related to the timing of neuronal differentiation. In addition, in several structures the expression of certain subunits (alpha 3, alpha 4 or beta 4) is transient, although not beta 2. Finally, the comparison of the different regional distribution patterns suggests that a limited number of structure-specific receptor isoforms are functional during development of CNS and PNS.

Animals↗