Internet in clinical research based on a pilot experience.

Computing has become an integral part of many disciplines nowadays, turning it into an evermore necessary working tool. Internet provides a fast and easy way to collect scientific data and is becoming a more and more effective and safe way to transmit data. It is also an efficient means for interaction and information sharing within a work group that provides the necessary flexibility.

Serotonin and carbachol induced suppression of synaptic responses in rat CA1 hippocampal area: effects of corticosteroid receptor activation in vivo.

Previous studies have shown that corticosteroids affect the changes in membrane potential evoked in CA1 hippocampal neurons by serotonin and the metabolically stable cholinergic analogue carbachol: Low corticosteroid levels induced by steroid administration to adrenalectomized rats or obtained in adrenally intact rats were associated with small transmitter responses. High corticosteroid levels induced by exogenous corticosteroid application or by an acute stress in adrenally intact rats generally evoked large transmitter responses. In the present study we investigated the consequences of this steroid modulation for the main stream of synaptic information in the CA1 hippocampal region, which is carried by amino acids.

Synaptic transmission in the rat dentate gyrus after adrenalectomy.

Granule cells in the rat hippocampal dentate gyrus contain intracellular receptors for the adrenal hormone corticosterone. Activation of these receptors seems essential for granule cell viability, since removal of the adrenal gland (adrenalectomy) results within three days in apoptotic-like degeneration of granule cells. In the present study we used extracellular in vitro recording methods to study the synaptic transmission in the dentate gyrus of adrenalectomized animals, in sham-operated controls and adrenalectomized rats treated with a low dose of corticosterone.

Serotonin and carbachol induced suppression of synaptic excitability in rat CA1 hippocampal area: effects of corticosteroid receptor activation.

Serotonin (5HT) and the cholinergic analogue carbachol (CCh) act on neurons in the hippocampal CA1 area through pre- and post-synaptic receptors. Previously, it was shown that post-synaptic actions of 5HT and CCh are affected by corticosteroids: predominant activation of high affinity mineralocorticoid receptors resulted in small hyperpolarizing responses to 5HT and small depolarizing responses to CCh; additional activation of low affinity glucocorticoid receptors led to increased 5HT and CCh responses. In the present study, we examined the consequences of steroid modulation of these post-synaptic membrane effects and/or possible pre-synaptic effects by 5HT and CCh for the excitability in the CA1 area, using extracellular field potential or intracellular recordings from individual pyramidal neurons.

Corticosteroid effects on electrical properties of brain cells: temporal aspects and role of antiglucocorticoids.

Pyramidal cells in the CA1 hippocampal area express both mineralo- and glucocorticoid receptors (MRs and GRs respectively) to which the rat adrenal hormone corticosterone binds effectively. Through activation of these receptors corticosteroids exert a delayed and persistent control over signal transduction in the hippocampus. Many cellular responses are affected by the hormone, including responsiveness to serotonin (5HT) and the cholinergic agent carbachol (CCh).

Hippocampal cell responses in mice with a targeted glucocorticoid receptor gene disruption.

Previous studies in rats have shown that cellular properties of hippocampal CA1 neurons are under coordinative control of mineralocorticoid and glucocorticoid receptors (MRs and GRs, respectively). In the present study, we examined electrical properties under conditions of exclusive MR occupation, by using mice with a genetic defect in GRs obtained by homologous recombination techniques. It appeared that in the animals homozygous for the genetic defect, the properties studied, i.

Cholinergic Responsiveness of Rat CA1 Hippocampal Neurons In Vitro: Modulation by Corticosterone and Stress.

Corticosterone can activate two corticosteroid receptor types in rat hippocampus: low doses activate mineralocorticoid receptors (MR) while high doses additionally activate glucocorticoid receptors (GR). We found that corticosterone, administered to adrenalectomized rats in vivo, dose-dependently modulates carbachol responsiveness of CA1 hippocampal neurons, recorded subsequently in vitro. Thus, the carbachol (3 µM) induced membrane depolarization in CA1 neurons was relatively large in hippocampal slices where either (almost) no corticosteroid receptors were activated (0-1 µg corticosterone/100g body weight) or where both MRs and GRs were occupied by high corticosterone doses (100-1000 µg/100g).

Modulation of 5HT1A responsiveness in CA1 pyramidal neurons by in vivo activation of corticosteroid receptors.

In this study we describe modulatory effects exerted by in vivo activation of corticosteroid receptors on 5HT responsiveness of rat CA1 pyramidal neurons. In the first series of experiments, adrenalectomized (ADX) rats were injected with corticosterone one hour prior to decapitation (1-1000 micrograms/100 g body weight) after which 5HT1A induced hyperpolarizations were determined in vitro by means of intracellular recordings. It appeared that 5HT responsiveness was dose-dependently affected by corticosterone injections: 5HT responses were relatively large when no corticosteroid receptors were activated (ADX); similar 5HT responses were observed or when both mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) were occupied by injection of high doses of corticosterone (100-1000 micrograms/100 g body weight).

Corticosteroid-mediated modulation of carbachol responsiveness in CA1 pyramidal neurons: a voltage clamp analysis.

Pyramidal neurons in the rat hippocampal CA1 area contain mineralocorticoid (MRs) and glucocorticoid (GRs) receptors for corticosterone. Previous current clamp experiments showed that depolarizations evoked by carbachol (1-3 microM) depend on relative MR/GR occupation: carbachol responses are small with predominant MR-activation and larger when both receptor types are occupied. Multiple K-conductances underlie the carbachol-induced depolarization.

Long-term control of neuronal excitability by corticosteroid hormones.

Hippocampal CA1 neurons express both mineralocorticoid and glucocorticoid receptors. Due to the difference in affinity of the two receptor types for corticosterone and variations in endogenous steroid levels, occupation of the receptors will range between a situation of predominant mineralocorticoid receptor activation and conditions where both receptor types are occupied. It was observed that local signal transduction is regulated by activation of the corticosteroid receptors.

Steroids and electrical activity in the brain.

Corticosteroid hormones can enter the brain and bind to two receptor subtypes: the high affinity mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) with approximately 10-fold lower affinity. Under physiological conditions the degree of receptor occupation will range from a predominant MR occupation (at the beginning of the inactive period, under rest) to concurrent activation of MRs and GRs (at the circadian peak and after stress). With in vitro electrophysiological recording techniques we observed that neuronal excitability in the CA1 hippocampal field is under a long-term control of MR- and GR-mediated events.

Modulation of carbachol responsiveness in rat CA1 pyramidal neurons by corticosteroid hormones.

Pyramidal neurons in the rat CA1 hippocampal area contain membrane receptors for acetylcholine but also intracellular receptors for the adrenal corticosteroid hormone corticosterone, i.e., mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs).

Structure and expression of the excision repair gene ERCC6, involved in the human disorder Cockayne's syndrome group B.

The human repair gene ERCC6--a presumed DNA (or RNA) helicase--has recently been found to function specifically in preferential nucleotide excision repair (NER). This NER subpathway is primarily directed towards repair of (the transcribed strand of) active genes. Mutations in the ERCC6 gene are responsible for the human hereditary repair disorder Cockayne's syndrome complementation group B, the most common form of the disease.

Mineralocorticoid hormones suppress serotonin-induced hyperpolarization of rat hippocampal CA1 neurons.

Pyramidal neurons in the rat CA1 hippocampal area contain intracellular mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) to which the adrenal hormone corticosterone can bind with differential affinity. The pyramidal neurons also have high amounts of 5-HT1a receptors, which mediate a membrane hyperpolarization. With intracellular recording in vitro, we found that selective occupation of MRs suppresses the 5-HT-induced hyperpolarization of CA1 pyramidal neurons.

Increased effect of noradrenaline on synaptic responses in rat CA1 hippocampal area after adrenalectomy.

Pyramidal neurons in the rat CA1 hippocampal area contain intracellular receptors for the steroid hormone corticosterone, and membrane associated alpha- and beta-adrenergic receptors. We compared the effect of noradrenaline (NA) on the synaptically evoked CA1 field potential in adrenalectomized (ADX) rats, where corticosteroid receptors are not occupied, with sham-operated controls. It appeared that the increase in the amplitude of the field potential induced by 10 microM NA was more pronounced in slices from ADX rats than in sham operated controls.