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Biomedical subjects

J M Sanz

Publications and source records attributed to J M Sanz.

At least 19 recordsLinked to original sources
PubMed2005

Production of doubled haploids in durum wheat (Triticum turgidum L.) through isolated microspore culture.

The objective of this work was to produce doubled haploid plants from durum wheat through the induction of androgenesis. A microspore culture technique was developed and used to produce fertile doubled haploid plants of agronomic interest. Five cultivars, one selected line, plus a collection of 20 F(1) crosses between different genotypes of high breeding value were used. Studies on several factors such as pre-treatments and media components were carried out in order to develop a protocol to regenerate green haploid plantlets. Anthers were pre-treated in 0.7 M mannitol. Microspores, from anther maceration, were plated on a C(17) induction culture medium with ovary co-culture. The optimum regeneration medium J25-8 was used. From 35 microspore isolations, 407 green plantlets were obtained. With this technique mature embryos were obtained. Green plants were regenerated from all genotypes used and approximately 67% of them were spontaneously doubled haploids. Some haploids and a very few polyploids plants were obtained. From the 407 plants, 275 were completely fertile and gave enough seeds to be assayed in the field. This protocol could be used complementary to or instead of the intergeneric crossing with maize as an economically feasible method to obtain doubled haploids from most durum wheat genotypes.

Benzyl Compounds↗
PubMed2005

Effects of lipids and aging on the neurotoxicity and neuronal loss caused by intracerebral injections of the amyloid-beta peptide in the rat.

The influence of diet and age on the area of lesion and on the neuronal density in the cerebral cortex was studied in rats following local injections of the amyloid-beta peptide (Abeta1-40) in PBS vehicle into the left frontal and cingulate cortices and compared with effects of injections of PBS alone into the corresponding regions of the right hemisphere The experiments were carried out in two groups of animals: one group of young adult rats and a second group of aged rats. Each group of animals, depending on the diet received, was divided into high-cholesterol, high-fat, and a control group. In order to evaluate the interaction of Abeta/PBS-cholesterol and of Abeta/PBS-fat, animals without dietary manipulation receiving Abeta and PBS injection were used as controls. The results showed that the greatest area of lesion was at Abeta injection sites in the high-cholesterol fed group of aged animals. The results also revealed a significant variance in the neuronal density by group and by injection type. Thus, high-cholesterol fed animals showed a greater reduction in neuronal density at Abeta and PBS-injected sites than that seen in the high-fat or control groups. The results also indicate that the loss of neurons at the Abeta injection site exceeds that seen in the PBS-injected area. The greatest reduction in the neuronal density was found at Abeta-injected site in the high-cholesterol fed group of aged animals. In conclusion, our findings indicate an interaction between lipids, age, and Abeta neurotoxicity, and might provide insights into the basic mechanisms involved in a short-term (acute-to-subchronic) response to Abeta peptide.

Aging↗
PubMed2005

Amyloid beta peptide-induced cholinergic fibres loss in the cerebral cortex of the rat is modified by diet high in lipids and by age.

The influence of diet and age on the effects of intracerebral injection of beta-amyloid peptide (Abeta1-40) in vehicle phosphate-buffered saline (PBS) and on the effects of vehicle alone on cholinergic fibres of the cerebral cortex was studied in rats. The experiments were carried in two groups of animals: one group of young adult rats and a second group of aged rats. Each group of animals, depending on the diet received, was divided into high-cholesterol, high-fat, and a control diet group. In order to evaluate the interaction of Abeta/PBS-cholesterol and of Abeta/PBS-fat, animals without dietary manipulation receiving Abeta and PBS injection were used as controls. High-cholesterol fed animals showed a statistically significant reduction of 49.62% in the number of cholinergic fibres at the Abeta injection site as compared with that at PBS injection site, while the high-fat and control animals showed a significant reduction of 28.13 and 26.81%, respectively. In all diet groups, the loss of cholinergic fibres caused by Abeta as compared to that caused by PBS injection was significantly greater in aged rats in comparison with that observed in the young animals. Furthermore, the results of a multivariate linear regression model revealed that the greatest reduction in cholinergic fibres was in the high-cholesterol fed animals (35 fibres/mm) as compared with that seen in the high-fat and control animals. A significantly greater reduction was also observed at Abeta injection site (28 fibres/mm) as compared with that caused by PBS injection, and a reduction of 16 cholinergic fibres per mm was found in aged animals as compared to that seen in young adult rats. These results show that high-cholesterol diet enhances the toxicity of Abeta peptide and that this is also age-dependent. Therefore, this study increases the evidences of the role of cholesterol in the pathology of Alzheimer's disease (AD).

Aging↗
PubMed2005

[Epidemiological and clinicopathological study of thyroid cancer in east Madrid].

OBJECTIVES: To analyze the incidence, clinical and histopathological manifestations, surgical complications, and prognostic factors of thyroid cancer in the east Madrid population. PATIENTS AND METHODS: Retrospective analysis of 141 consecutive diagnosed of thyroid cancer in our area between 1985 and 2001. Median follow-up was 4,5 years. RESULTS: The annual incidence rate was 4.74/100,000 inhabitants and the female:male proportion 3.5:1. The average age of patients at diagnosis was 44.5 years and nodular goiter was the principal type of clinical presentation (74.5%). The most frequent histological variant was papillary thyroid carcinoma (69%). Total thyroidectomy was carried out in 86% patients. 9.6% patients suffered permanent hypoparathyroidism and 3.3% paralysis of recurrent laryngeal nerve. Radioactive iodine ablation of remaining thyroid was carried out in 91 patients. Residual disease or local recurrence was observed on follow-up in 21% of patients, and metastasis at a distant site in 9%. 7.9% died along follow-up. The principal prognostic factors for metastasis or death were age, histological type, tumor size, local invasion and existence of metastasis at the time of diagnosis. CONCLUSIONS: The incidence of thyroid cancer in our population was high, especially in women. Although the proportion of postsurgical complications was elevated, global prognosis is good and some factors related to it have been identified. Increase of thyroglobulin plasma level at follow-up is a good recurrence indicator of the disease, especially with regard to distant metastases.

Adult↗
PubMed2001

Nucleotide receptors: an emerging family of regulatory molecules in blood cells.

Nucleotides are emerging as an ubiquitous family of extracellular signaling molecules. It has been known for many years that adenosine diphosphate is a potent platelet aggregating factor, but it is now clear that virtually every circulating cell is responsive to nucleotides. Effects as different as proliferation or differentiation, chemotaxis, release of cytokines or lysosomal constituents, and generation of reactive oxygen or nitrogen species are elicited upon stimulation of blood cells with extracellular adenosine triphosphate (ATP). These effects are mediated through a specific class of plasma membrane receptors called purinergic P2 receptors that, according to the molecular structure, are further subdivided into 2 subfamilies: P2Y and P2X. ATP and possibly other nucleotides are released from damaged cells or secreted via nonlytic mechanisms. Thus, during inflammation or vascular damage, nucleotides may provide an important mechanism involved in the activation of leukocytes and platelets. However, the cell physiology of these receptors is still at its dawn, and the precise function of the multiple P2X and P2Y receptor subtypes remains to be understood.

Animals↗
PubMed2001

[Basal concentrations of gastrin and pepsinogen I and II in gastric ulcer: influence of Helicobacter pylori infection and usefulness in the control of the eradication].

AIM: To study the influence of Helicobacter pylori eradication on basal gastrin and pepsinogen I and II levels in patients with gastric ulcer over a 1-year follow-up period, and to assess the usefulness of these values in confirming H. pylori eradication after treatment. METHODS: Fifty-six patients with gastric ulcer and H. pylori infection were prospectively studied. At the beginning of the study, endoscopy with biopsies for histologic examination and urease testing was carried out, as were 13C-urea breath test and blood samples for determination of gastrin and pepsinogen I and II values by radioimmunoassay and serology. Histologic study, 13C-urea breath test and laboratory determinations were repeated at months 1, 6 and 12 after completion of eradication treatment. RESULTS: H. pylori infection was eradicated in 82.1% of patients. In patients with successful H. pylori eradication, the initial mean gastrin value was 75.5 +/- 39.1 pg/ml, while at 1 month after treatment this value decreased to 49.2 +/- 21 pg/ml (p < 0.0001). No further reductions were noted. Initial pepsinogen I and II values were 104 +/- 58 and 15.8 +/- 10 ng/ml, respectively, whereas at month 1 after treatment these values were 77 +/- 42 and 7.3 +/- 4 ng/ml, respectively (p < 0.0001) and were 72 +/- 41 and 6.7 +/- 3 ng/ml respectively at month 6 (p < 0.01); no further variations were observed thereafter. The area under the ROC curve which reveals eradication through reductions in hormonal values was 0.70 for gastrin, 0.78 for pepsinogen I, 0.93 for pepsinogen II and 0.92 for the pepsinogen I/II ratio. At months 6 and 12 after treatment completion, differences in mean gastrin and pepsinogen I and II values between the patients with normal histologic findings and those with chronic gastritis were significant (p < 0.05). CONCLUSIONS: a) H. pylori eradication is associated with an early fall in basal gastrin values and a progressive decrease in basal pepsinogen I and II values. b) In patients with gastric ulcer, determination of the decrease in basal pepsinogen II levels is a useful and early non-invasive method for confirming eradication. c) Determination of gastrin and pepsinogen I and II values may be useful for assessing improvement in gastritis 6 months after treatment completion.

Area Under Curve↗
PubMed2001

Glutamatergic components of the retrosplenial granular cortex in the rat.

The ultrastructural characteristics, distribution and synaptic relationships of identified, glutamate-enriched thalamocortical axon terminals and cell bodies in the retrosplenial granular cortex of adult rats is described and compared with GABA-containing terminals and cell bodies, using postembedding immunogold immunohistochemistry and transmission electron microscopy in animals with injections of cholera toxin- horseradish peroxidase (CT-HRP) into the anterior thalamic nuclei. Anterogradely labelled terminals, identified by semi-crystalline deposits of HRP reaction product, were approximately 1 microm in diameter, contained round, clear synaptic vesicles, and established asymmetric (Gray type I) synaptic contacts with dendritic spines and small dendrites, some containing HRP reaction product, identifying them as dendrites of corticothalamic projection neurons. The highest densities of immunogold particles following glutamate immunostaining were found over such axon terminals and over similar axon terminals devoid of HRP reaction product. In serial sections immunoreacted for GABA, these axon terminals were unlabelled, whereas other axon terminals, establishing symmetric (Gray type II) synapses were heavily labelled. Cell bodies of putative pyramidal neurons, containing retrograde HRP label, were numerous in layers V-VI; some were also present in layers I-III. Most were overlain by high densities of gold particles in glutamate but not in GABA immunoreacted sections. These findings provide evidence that the terminals of projection neurons make synaptic contact with dendrites and dendritic spines in the ipsilateral retrosplenial granular cortex and that their targets include the dendrites of presumptive glutamatergic corticothalamic projection neurons.

Animals↗
PubMed2001

Proinflammatory cytokines inhibit secretion in rat bile duct epithelium.

BACKGROUND AND AIMS: Cholestatic disorders often are associated with portal inflammation, but whether or how inflammation contributes to cholestasis is unknown. Thus we studied the effects of proinflammatory cytokines on bile duct epithelia secretory mechanisms. METHODS: Isolated bile duct units (IBDUs) were cultured with interleukin (IL)-6, interferon gamma, tumor necrosis factor (TNF)-alpha, and IL-1 alone or in combination. Ductular secretion was measured using video-optical planimetry. Bicarbonate and Cl(-) transport were assessed microfluorimetric measuring pH(i) (BCECF) and [Cl(-)](i) transients (MEQ). Expression of Cl(-)/HCO(3)(-) exchanger (AE-2), cystic fibrosis transmembrane conductance regulator (CFTR), and the secretin receptor (SR) were assessed by ribonuclease protection assay. Cellular cyclic adenosine monophosphate (cAMP) levels were studied by enzymatic immunoassay. Paracellular permeability was assessed using fluorescein-labeled dextrans (FD) in cholangiocyte monolayers (NRC-1). RESULTS: Although not effective when given alone, each combination of IL-6, interferon gamma, IL-1, and TNF-alpha inhibited secretion in IBDU. Cytokines inhibited cAMP formation, AE-2 activity, and cyclic AMP-dependent Cl(-) efflux, but not that induced by purinergic agonists. AE-2 gene expression was unaffected by proinflammatory cytokines, whereas CFTR and SR expression was increased. In addition, paracellular transit of FD across NRC-1 monolayers was increased. CONCLUSIONS: Inflammatory cytokines inhibit cAMP-dependent fluid secretion in cholangiocytes and impair the barrier functions of biliary epithelia. These changes may represent the molecular mechanisms by which inflammation leads to ductular cholestasis in vivo.

Animals↗
PubMed2000

Structural differences between Saccharomyces cerevisiae ribosomal stalk proteins P1 and P2 support their functional diversity.

The eukaryotic acidic P1 and P2 proteins modulate the activity of the ribosomal stalk but playing distinct roles. The aim of this work was to analyze the structural features that are behind their different function. A structural characterization of Saccharomyces cerevisaie P1 alpha and P2 beta proteins was performed by circular dichroism, nuclear magnetic resonance, fluorescence spectroscopy, thermal denaturation, and protease sensitivity. The results confirm the low structure present in both proteins but reveal clear differences between them. P1 alpha shows a virtually unordered secondary structure with a residual helical content that disappears below 30 degrees C and a clear tendency to acquire secondary structure at low pH and in the presence of trifluoroethanol. In agreement with this higher disorder P1 alpha has a fully solvent-accessible tryptophan residue and, in contrast to P2 beta, is highly sensitive to protease degradation. An interaction between both proteins was observed, which induces an increase in the global secondary structure content of both proteins. Moreover, mixing of both proteins causes a shift of the P1 alpha tryptophan 40 signal, pointing to an involvement of this region in the interaction. This evidence directly proves an interaction between P1 alpha and P2 beta before ribosome binding and suggests a functional complementation between them. On a whole, the results provide structural support for the different functional roles played by the proteins of the two groups showing, at the same time, that relatively small structural differences between the two stalk acidic protein types can result in significant functional changes.

Amino Acid Sequence↗
PubMed2000

[Effects of Helicobacter pylori eradication on the recurrence of gastric ulcer during a 12-month follow up].

BACKGROUND: To study the influence of Helicobacter pylori eradication on the incidence of ulcer recurrence during 12 months of follow-up in gastric ulcer patients. PATIENTS AND METHOD: Seventy-three patients with gastric ulcer were prospectively studied. At endoscopy two biopsies from both antrum and body for haematoxylin-eosin staining and one for rapid urease test were obtained. Likewise, serology and 13C-urea breath test were carried out. Fifty-six H. pylori infected patients were monitored after giving an eradication therapy with omeprazole, clarithromycin and amoxicillin. A first control endoscopy was performed immediately after completing treatment to confirm ulcer healing. A second control endoscopy (with histologic study) and a breath test were performed one month after completing therapy (eradication was defined as the absence of H. pylori by both methods). Finally, an endoscopy was repeated at 6 and 12 months to study ulcer recurrences. RESULTS: Mean age was 54 +/- 13 years (69% males). Cumulative ulcer recurrence rate for 12 months, respectively for patients with eradication success and failure, was 2.3% (95% CI, 0-12%) and 70% (34-93%) (chi 2: 23.9; p < 0.0001). Comparison between Kaplan-Meier curves for ulcer recurrence depending on H. pylori eradication showed significant differences (log-rank test; chi 2: 33.8; p < 0.0001). A patient successfully treated underwent ulcer recurrence while receiving treatment with acetylsalicylic acid, without recurrence of the infection. CONCLUSIONS: H. pylori eradication is associated with a dramatic reduction on the recurrence of gastric ulcer, with a cumulative recurrence rate during 12 months of only 2.3%, which suggests that definitive cure of gastric ulcer disease is possible by means of microorganism eradication.

Adult↗
PubMed2000

1H NMR structural characterization of a nonmitogenic, vasodilatory, ischemia-protector and neuromodulatory acidic fibroblast growth factor.

A shortened genetically engineered form of acidic fibroblast growth factor (aFGF), that includes amino acids 28-154 of the full-length sequence (154 residues) plus Met in substitution of Leu27, does not induce cell division even though it is recognized by the cell membrane receptor, triggers the early mitogenic events, and retains the neuromodulatory, vasoactive, and cardio- and neuroprotective properties of the native full-length molecule. Taken together, these properties make this truncated aFGF a promising compound in the treatment of a wide assortment of neurological and cardiovascular pathologies where aFGF mitogenic activity is dispensable. Differences in biological activities between the shortened aFGF and the wild-type form have been attributed to lack of stability, and to the specific amino acid sequence missing at the N-terminus. Here we show that this shortened aFGF form has a three-dimensional structure even more stable than the wild-type protein at the mitogenic assay conditions; that this structure is similar to that of the wild type except at site 1 of interaction with the cell membrane receptor; that its lack of mitogenic activity cannot be attributed to the specific missing sequence; and that the vasodilatory activity of aFGF seems impaired by alterations of the three-dimensional structure of site 2 of interaction with the cell membrane receptor.

Amino Acid Sequence↗
PubMed2000

Kinetics and mechanism of ATP-dependent IL-1 beta release from microglial cells.

Endotoxin-dependent release of IL-1 beta from mouse microglial cells is a very inefficient process, as it is slow and leads to accumulation of a modest amount of extracellular cytokine. Furthermore, secreted IL-1 beta is mostly in the procytokine unprocessed form. Addition of extracellular ATP to LPS-primed microglia caused a burst of release of a large amount of processed IL-1 beta. ATP had no effect on the accumulation of intracellular pro-IL-1 beta in the absence of LPS. In LPS-treated cells, ATP slightly increased the synthesis of pro-IL-1 beta. Optimal ATP concentration for IL-1 beta secretion was between 3 and 5 mM, but significant release could be observed at concentrations as low as 1 mM. At all ATP concentrations IL-1 beta release could be inhibited by increasing the extracellular K+ concentration. ATP-dependent IL-1 beta release was also inhibited by 90 and 60% by the caspase inhibitors YVAD and DEVD, respectively. Accordingly, in ATP-stimulated microglia, the p20 proteolytic fragment derived from activation of the IL-1-beta-converting enzyme could be detected by immunoblot analysis. These experiments show that in mouse microglial cells extracellular ATP triggers fast maturation and release of intracellularly accumulated IL-beta by activating the IL-1-beta-converting enzyme/caspase 1.

Adenosine Triphosphate↗
PubMed2000

Concordance between noninvasive tests in detecting Helicobacter pylori and potential use of serology for monitoring eradication in gastric ulcer.

Our aim was to determine concordance between 13C-urea breath test and serology in detecting Helicobacter pylori and to study their potential use for monitoring eradication in patients with gastric ulcer. We prospectively studied 73 gastric ulcer patients. On endoscopy, biopsies were taken for hematoxylineosin staining and rapid urease testing. Blood samples were drawn for immunoglobulin G antibody determination by enzyme-linked immunosorbent assay (ELISA). A 13C-urea breath test was performed as well. Histology, serology, and urea breath tests were all repeated 1, 6, and 12 months after therapy completion in 56 infected patients. A proportion of positive agreement between serology and breath test results as high as 0.95 was found. McNemar statistic was 3 (p = 0.08), whereas kappa statistic was 0.83 (p < 0.0001). At month 6, significant differences in patients successfully treated relative to baseline serologic values were observed (chi2 = 11.7; p < 0.001). The area under the receiver operating characteristic (ROC) curve for diagnostic efficiency was 0.76, sensitivity was 74%, and specificity was 90% (for H. pylori eradication) when the fall of at least one category in serologic levels was considered as cut-off point. No further decreases in serologic levels were noted over the next 6 months, and 48.8% of patients remained seropositive 1 year after completion of successful treatment. A high concordance between serology and 13C-urea breath test results is observed when the two procedures are used for H. pylori infection diagnosis in patients with gastric ulcer. Also, serology can be successfully used for monitoring H. pylori eradication 6 months after therapy completion.

Adult↗
PubMed1999

Structural and functional study of a conserved region in the uncoupling protein UCP1: the three matrix loops are involved in the control of transport.

It has been reported that the region 261-269 of the uncoupling protein from brown adipose tissue mitochondria, UCP1, has an important role in the control of its proton translocating activity. Thus the deletion of residues Phe267-Lys268-Gly269 leads to the loss of the nucleotide regulation of the protein, while the complete deletion of the segment leads to the formation of a pore. The region displays sequence homology with the DNA-binding domain of the estrogen receptor. The present report analyzes the structure, by NMR and circular dichroism, of a 20 amino acid residue peptide containing the residues of interest. We demonstrate that residues 263-268 adopt an alpha-helical structure. The helix is at the N-terminal end of the sixth transmembrane domain. The functional significance of this helix has been examined by site-directed mutagenesis of the protein expressed recombinantly in yeasts. Alterations in the structure or orientation of the region leads to an impairment of the regulation, by nucleotides and fatty acids, of the transport activity. UCP1 is one member of the family formed by the carriers of the mitochondrial inner membrane. The family is characterized by a tripartite structure with three repeated segments of about 100 amino acid residues. Two of the mutations have also been performed in the first and second matrix loops and the effect on UCP1 function is very similar. We conclude that the three matrix loops contribute to the formation of the gating domain in UCP1 and propose that they form a hydrophobic pocket that accommodates the purine moiety of the bound nucleotide.

Adipose Tissue↗
PubMed1999

ATP receptors and giant cell formation.

We have investigated the role of the purinergic P2X7 receptor in the formation of multinucleated giant cells in human monocyte/macrophage cultures stimulated with either concanavalin A or phytohemagglutinin. Macrophage fusion can be blocked by a P2X7-selective pharmacological antagonist or by a mAb directed against the extracellular P2X7 domain. Furthermore, macrophage cell clones expressing high P2X7 levels spontaneously fuse in culture, whereas macrophage clones lacking P2X7 are unable to fuse. Our findings suggest that the newly identified purinergic P2X7 receptor plays a central role in the complex chain of events leading to generation of macrophage-derived giant cells.

Giant Cells↗
PubMed1999

Immunoelectron microscopic study of gamma-aminobutyric acid inputs to identified thalamocortical projection neurons in the anterior thalamus of the rat.

We have carried out a semi-quantitative ultrastructural study to determine the characteristics and distribution of gamma-aminobutyric acid (GABA)-containing constituents of the anterodorsal (AD) and anteroventral (AV) thalamic nuclei in adult rats. We used a polyclonal antibody to GABA and a postembedding immunogold detection method in animals in which the cortical projection neurons of these nuclei had been labelled by retrograde transport of cholera toxin/horseradish peroxidase (HRP) injected into the retrosplenial granular cortex. Two types of GABA-immunopositive structures were identified, with gold particle densities 4-40 times higher than the highest densities over blood-vessel lumens and areas of empty resin: (1) an apparently homogeneous population of axon terminals with Gray type-2 (symmetric) synaptic contacts corresponding to F-axon terminals; and (2) small-medium sized myelinated axons scattered individually or in small groups within the neuropil which may be their parent axons. These axons and terminals may originate from the ipsilateral thalamic reticular nucleus; others may arise from the basal forebrain or brainstem. The GABA-immunopositive terminals comprised approximately 16% of all axon terminal profiles in AD and 12% in AV, a significant difference. However, because the immunoreactive axon terminals in AD were significantly larger than those in AV (1.09+/-0.47 microm2 vs 0.90+/-0.43 microm2) and would therefore be encountered more frequently, it is not possible to conclude that the GABAergic innervation of AD is heavier than that of AV. The GABA-positive terminals established synaptic contacts with cell bodies and dendrites of all sizes (some of which were HRP-labelled) with the following frequency distribution (AD/AV, no significant difference): somata 5%/7%; large dendrites (> or = 1.5 microm) 14%/9%; medium dendrites (1.00-1.49 microm) 35%/45% and small dendrites (< 1 microm) 46%/40%. Despite evidence from previous studies, we found no evidence in this study for the presence of GABAergic interneurons or for GABA-containing projection neurons in AD or AV.

Animals↗
PubMed1999

Neurotransmitter characteristics of neurons projecting to the supramammillary nucleus of the rat.

Retrograde labelling was combined with immunohistochemistry to localize neurons containing choline acetyltransferase, gamma-aminobutyric acid (GABA), glutamate, serotonin, somatostatin, Leu-enkephalin, neurotensin, and substance P-immunoreactivity in neurons projecting to the supramammillary nucleus in the rat. Injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the supramammillary nucleus resulted in retrogradely labelled neurons in the medial septal nucleus, the nuclei of the diagonal band of Broca, the infralimbic cortex, the medial and lateral preoptic nucleus, the subiculum, the laterodorsal tegmental nucleus, the compact subnucleus of the central superior nucleus and the dorsal raphe nucleus. In the medial septal nucleus and in the nuclei of the diagonal band of Broca, 80-85% of WGA-HRP- labelled neurons (30-40 per section) were also immunoreactive for choline acetyltransferase and small numbers of WGA-HRP-labelled neurons were immunoreactive for GABA, glutamate, neurotensin or substance P. In the medial preoptic nucleus, 85-90% of retrogradely labelled neurons (25-30 per section) were immunoreactive for somatostatin and a few WGA-HRP-labelled neurons displayed neurotensin-immunoreactivity. In the rostroventral part of the subiculum, small numbers of retrogradely labelled neurons were also immunoreactive for neurotensin or for glutamate. In the laterodorsal tegmental nucleus, 90% of WGA-HRP-labelled neurons (20-25 per section) were immunoreactive for choline acetyltransferase and small numbers of retrogradely labelled neurons also displayed substance P immunoreactivity. In the compact subnucleus of the central superior nucleus, 50-60% of retrogradely labelled neurons (15-20 per section) were also immunolabelled for GABA and approximately 30-40% of WGA-HRP-labelled neurons (10-12 per section) were immunoreactive for Leu-enkephalin. The compact subnucleus of the central superior nucleus also contained small numbers of retrogradely labelled neurons that displayed neurotensin immunoreactivity. In the dorsal raphe nucleus, 80-85% of WGA-HRP- labelled neurons (30-40 per section) were also immunoreactive for serotonin and small numbers of retrogradely labelled neurons displayed neurotensin or glutamate immunoreactivity. These results suggest that the multiple neurochemicals contained in ascending and descending projections to the SuM participate in complex interactions in the transmission process of SuM neurons.

Animals↗