Biomedical subjects

Susana Aznar

Publications and source records attributed to Susana Aznar.

7 recordsLinked to original sources

PubMed2006

Serotonin depletion results in a decrease of the neuronal activation caused by rivastigmine in the rat hippocampus.

Interactions between the serotonergic and cholinergic systems are known to occur and are believed to play a role in the mechanism underlying both major depression and Alzheimer's disease. On a molecular level, studies suggest that acetylcholine (ACh) increases serotonin (5-HT) release through nicotinic receptors located at nerve terminals. The aim of the present study was to determine in which areas and to what extent 5-HT mediates the neuronal response to ACh release. For this purpose, neuronal activity was measured in rats with rivastigmine-induced elevated ACh levels after a 95% 5-HT depletion obtained by dosing p-chlorophenylalanine followed by D,L-fenfluramine. Neuronal activation was quantified by stereological measurements of c-Fos immunoreactivity. The brain areas examined were medial prefrontal cortex, septum, dorsal hippocampus, and dorsal raphe nucleus. Rivastigmine significantly increased c-Fos immunoreactivity in medial prefrontal cortex and the hippocampus, but not in the septum and dorsal raphe nucleus. 5-HT depletion decreased ACh-induced c-Fos immunoreactivity in the dentate gyrus. By contrast, 5-HT depletion had no effect on the ACh-induced activity in the other brain areas examined. It is concluded that 5-HT mediates part of the ACh-induced hippocampal neuronal activation, possibly mediated via locally released 5-HT.

Acetylcholine↗

PubMed2006

Immunodetection of the serotonin transporter protein is a more valid marker for serotonergic fibers than serotonin.

Tracking serotonergic pathways in the brain through immunodetection of serotonin has widely been used for the anatomical characterization of the serotonergic system. Immunostaining for serotonin is also frequently applied for the visualization of individual serotonin containing fibers and quantification of serotonin positive fibers has been widely used to detect changes in the serotonergic innervation. However, particularly in conditions with enhanced serotonin metabolism the detection level of serotonin may lead to an underestimation of the true number of serotonergic fibers. The serotonin transporter (SERT) protein, on the other hand, is less liable to metabolism and for that reason we hypothetized that SERT immunostaining is a more stable marker of serotonergic fibers. Rats were pretreated with monoamine oxidase (MAO) inhibitor and compared with placebo treated rats. Brains were double immunostained for serotonin and SERT protein and colocalization was quantified in several brain areas by confocal microscopy. In comparison with untreated rats, MAO inhibitor treated rats had a significantly higher number (almost 200% increase) of serotonin immunopositive fibers whereas no difference was observed in the number of the SERT positive fibers. Colocalization between serotonin and SERT positive fibers was close to 100% in MAO inhibitor treated animals but only 30% in untreated rats. We conclude that the rapid metabolism of serotonin leads to an underestimation of immunodetected serotonergic fibers and that in many instances, SERT immunostaining may be a better indicator of serotonergic fibers.

Animals↗

PubMed2006

Physical activity during treatment in children with leukemia: a pilot study.

The purpose of this pilot study was to measure physical activity (PA) levels in children undergoing treatment for acute lymphoblastic leukemia (ALL) and to compare the results with those from age-matched healthy children. We used the MTI Actigraph accelerometer to determine PA (during a 1 week period) in children (n = 7; age = 4-7 y) undergoing maintenance treatment for ALL and in age-matched controls (n = 7). The number of children accumulating at least 60 min of moderate-to-vigorous physical activity (MVPA) for 5 or more days of the week was 3 for the control group, whereas no children with ALL met this criterion. Significantly lower levels of total weekly time of MVPA were seen in children being treated for ALL (328 +/- 107 min) than in controls (506 +/- 175 min) (p < 0.05). When weekday data was analyzed, the ALL patients also had significantly lower mean daily times of MVPA (49 +/- 23 min vs. 79 +/- 25 min). It is thus important that young ALL sufferers are encouraged to participate in appropriate sports, games, and physical activities both in the family and school environments that will prime them with positive attitudes to PA during the critical early years of life.

Antineoplastic Agents↗

PubMed2005

Central serotonin depletion affects rat brain areas differently: a qualitative and quantitative comparison between different treatment schemes.

Depletion of rat brain serotonin (5-hydroxytryptamin, 5-HT) has been widely used to study effects of serotonin and its interaction with other transmitter systems. Various treatment regimes for serotonin depletion have been applied, but the efficacy of these seems to vary considerably. So far, no studies have systematically examined and compared different approaches. The present work combines quantitative and qualitative measurements and compares six different treatment schemes for 5-HT depletion. Treatment outcome was evaluated by HPLC measurements of 5-HT and 5-HIAA concentrations, and by 5-HT and tyrosine hydroxylase immunocytochemistry. The schemes included repeated administration of fenfluramine (FEN) and/or p-chlorophenylalanine (pCPA). The most efficient treatment for rat brain 5-HT depletion was the combined treatment with one daily pCPA (200 mg/kg) injection for 3 days followed by one injection of d,l-FEN (20 mg/kg) on the fourth day, causing a 94.9% brain 5-HT depletion. Immunostaining revealed a distinct brain distribution of the remaining 5-HT, with an almost complete depletion of 5-HT in the cerebral cortex, hippocampus and thalamus, while a substantial amount of 5-HT still was left in the raphe nuclei, the medial forebrain bundle, and the medial eminence. FEN or pCPA treatment alone caused from 68.2 to 94.0% decrease in 5-HT levels. While the pattern of 5-HT depletion using pCPA alone was comparable to the one seen with the combined treatment, the 5-HT depletion using FEN alone showed a different pattern with 5-HT distributed in several brain regions.

Animals↗

PubMed2005

Alpha 7 nicotinic receptor subunit is present on serotonin neurons projecting to hippocampus and septum.

The serotonergic transmitter system regulates hippocampal activity through its raphe projection to hippocampus and medial septum/diagonal band of Broca complex (MS/DBB), and most likely also indirectly through its interaction with the cholinergic neurotransmitter system. Nicotine, e.g., enhances hippocampal serotonin release probably through presynaptic nicotinic receptors. We investigated the possible presence of the alpha 7-nicotinic subunit on serotonergic neurons projecting to hippocampus and MS/DBB. By retrograde neuronal tracing, hippocampal serotonergic neurons were identified and with double fluorescence immunostaining and Alexa-488 bound alpha-bungarotoxin the presence of active alpha 7 receptor on their soma was determined. Most of the retrogradely labeled serotonin neurons contained the alpha 7 subunit. A low degree of colocalization between alpha-bungarotoxin and serotonin-positive neurons suggest that the alpha 7 subunit may be transported anterogradely to the serotonergic axonal terminals.

Animals↗

PubMed2004

No effect of MDMA (ecstasy) on cell death and 5-HT2A receptor density in organotypic rat hippocampal cultures.

MDMA (3,4 Methylenedioxy-methamphetamine) binds and blocks the presynaptic serotonin reuptake transporters and postsynaptic serotonin 5-HT2A receptors, with highest affinity for the first. Whether 5-HT2A receptor density decreases due to MDMA's direct effect on postsynaptic serotonin receptors is at present not known. This study analyzes whether direct stimulation of the postsynaptic 5-HT2A receptor by MDMA in organotypic hippocampal cultures results in cell death and downregulation of this receptor. Fifty or 100 microM MDMA was added to 1 week old cultures, made of 11 day old rat pups. Fluorojade and immunostaining for MAP2 and 5-HT2A to determine neurodegeneration, and changes in receptor density, respectively, resulted in no significant differences. MDMA's neurotoxicity and regulation of post-synaptic 5-HT2A receptors thus seems to require the presence of intact serotonergic terminals.

Animals↗

PubMed2003

The 5-HT1A serotonin receptor is located on calbindin- and parvalbumin-containing neurons in the rat brain.

The 5-HT(1A) receptor is a well-characterized serotonin receptor playing a role in many central nervous functions and known to be involved in depression and other mental disorders. In situ hybridization, immunocytochemical, and binding studies have shown that the 5-HT(1A) receptor is widely distributed in the rat brain, with a particularly high density in the limbic system. The receptor's localization in the different neuronal subtypes, which may be of importance for understanding its role in neuronal circuitries, is, however, unknown. In this study we show by immunocytochemical double-labeling techniques, that the 5-HT(1A) receptor is present on both pyramidal and principal cells, and calbindin- and parvalbumin-containing neurons, which generally define two different subtypes of interneurons. Moreover, semiquantitative analysis showed that the receptor's distribution in the different neuronal types varies between brain areas. In cortex, hippocampus, hypothalamus, and amygdala the receptor was located on both principal cells and calbindin- and parvalbumin-containing neurons. In septum and thalamus, the receptor was mostly present on calbindin- and parvalbumin-containing cells. Especially in the medial septum and thalamic reticular nucleus, the receptor highly colocalized with parvalbumin-positive neurons. These results suggest a diverse function of the 5-HT(1A) receptor in modulating neuronal circuitry in different brain areas, that may depend on the type of neuron the receptor is predominantly located on.

Animals↗