Suppressed proliferation and apoptotic changes in the rat dentate gyrus after acute and chronic stress are reversible.

Acute stress suppresses new cell birth in the hippocampus in several species. Relatively little is known, however, on how chronic stress affects the turnover, i.e.

Gene expression patterns in rat dentate granule cells: comparison between fresh and fixed tissue.

RNA from brain tissue (in particular human brain) can often only be extracted from fixed material. As brain tissue is very heterogeneous with regard to cell type, it is important to obtain RNA from small samples of identified cells. The aim of this study was (a) to generate expression profiles from small yet homogeneous samples of fixed brain cells in rat and (b) to verify the reliability of these profiles by comparing them with expression profiles obtained from single fresh neurons of the same cell type.

Acute stress increases calcium current amplitude in rat hippocampus: temporal changes in physiology and gene expression.

Activation of hippocampal glucocorticoid receptors in vitro increases calcium current amplitude through a process requiring DNA binding of receptor homodimers. We here investigated (i). whether similar increased calcium currents also occur following in vivo glucocorticoid receptor activation due to stress and (ii).

Chronic unpredictable stress causes attenuation of serotonin responses in cornu ammonis 1 pyramidal neurons.

In the present study, serotonin (5-HT) responses of hippocampal pyramidal cornu ammonis 1 (CA1) neurons were studied in rats subjected twice daily for 21 days to unpredictable stressors. In hippocampal tissue from thus stressed rats mRNA expression of the 5-HT(1A) receptor and mineralo- as well as glucocorticoid receptors were examined with in situ hybridization. On average, stressed rats displayed increased adrenal weight and attenuated body weight gain compared with controls, supporting that the animals had experienced increased corticosterone levels due to the stress exposure.

Chronic unpredictable stress impairs long-term potentiation in rat hippocampal CA1 area and dentate gyrus in vitro.

Rises in corticosteroid levels, e.g. after acute stress, impair synaptic plasticity in the rat hippocampus when compared with the situation where levels are basal, i.

Gene expression changes in single dentate granule neurons after adrenalectomy of rats.

Removal of corticosterone by adrenalectomy induces apoptosis 3 days later, in some, but not all, rat dentate granule cells. We hypothesized that individual dentate cells trigger specific gene expression profiles that partly determine their apoptosis susceptibility. RNA was collected from physiologically characterized granule cells at 2 or 3 days after adrenalectomy or sham operation, and linearly amplified.

Effect of chronic stress on synaptic currents in rat hippocampal dentate gyrus neurons.

We investigated the effect of chronic stress on synaptic responses of rat dentate granule cells to perforant path stimulation. Rats were subjected for 3 wk to unpredictable stressors twice daily or to control handling. One day after the last stressor, hippocampal slices were prepared and synaptic responses were determined with whole-cell recording.

Effect of adrenalectomy on miniature inhibitory postsynaptic currents in the paraventricular nucleus of the hypothalamus.

Within the rat paraventricular nucleus of the hypothalamus two types of neurons have been distinguished based on morphological appearance, i.e., parvocellular and magnocellular neurons.

Corticosterone and stress reduce synaptic potentiation in mouse hippocampal slices with mild stimulation.

Elevation of circulating corticosterone levels, either through exogenous administration of the hormone or following stress exposure, is known to reduce hippocampal synaptic potentiation in rodents. It is presently debated whether this reduction is due to activation of hippocampal glucocorticoid receptors or is primarily caused in other brain structures projecting to the hippocampus. To address this issue, we examined whether synaptic potentiation in hippocampal slices from mice with low basal corticosterone levels was altered 1-4 h after a brief in vitro administration of 100 nM corticosterone.

Glucocorticoids alter calcium conductances and calcium channel subunit expression in basolateral amygdala neurons.

Glucocorticoid hormones, which are released in high amounts after stress, enter the brain where they bind to intracellular receptors that are abundant in limbic areas, in particular the hippocampus and amygdala nuclei. Behavioural studies indicate that glucocorticoids modulate learning and memory processes via receptors in the hippocampus and amygdala. So far, the effects of glucocorticoids on amygdala neurons have not been investigated at the cellular and molecular level.

Hippocampal serotonin responses in short and long attack latency mice.

Short and long attack latency mice, which are selected based on their offensive behaviour in a resident-intruder model, differ in their neuroendocrine regulation as well as in aspects of their brain serotonin system. Previous studies showed that the binding capacity and expression of serotonin-1A receptors in the hippocampal CA1 field of long attack latency mice are significantly lower than that found in short attack latency mice. We tested whether the functional responses of CA1 hippocampal cells to serotonin are also reduced in long attack latency mice.

Reduced field response to perforant path stimulation after adrenalectomy: effect of nimodipine treatment.

Adrenalectomy enhances apoptosis in the rat dentate gyrus and concurrently decreases the field response of dentate cells to perforant path stimulation. Recent data showed that calcium current amplitude is increased 1 day prior to the appearance of apoptotic cells, pointing to calcium as a risk factor for the onset of apoptosis. We here tested if in vivo administration of nimodipine-thus presumably reducing dentate calcium influx through L type calcium channels-prevents the appearance of apoptotic cells and the change in field responses after adrenalectomy.

Morphological and functional properties of rat dentate granule cells after adrenalectomy.

After complete adrenalectomy, part of the granule cells in the dentate gyrus undergo apoptosis. Findings on morphological changes in non-apoptotic granule cells, though, have been equivocal. In the present study we examined the dendritic trees of dentate granule cells 7 days after adrenalectomy or sham operation, and tested the hypothesis that changes in dendritic trees have considerable consequences for ionic currents, as measured in the soma with whole cell recording.

Point mutation in the mouse glucocorticoid receptor preventing DNA binding impairs spatial memory.

Activation of central glucocorticoid receptors caused by the stress that is associated with a learning task facilitates storage of the acquired information. The molecular mechanism underlying this phenomenon is entirely unknown. Glucocorticoid receptors can influence transcription both through DNA binding-dependent and -independent mechanisms.

Calcium currents in rat dentate granule cells are altered after adrenalectomy.

Adrenal corticosteroid hormones modulate voltage-gated calcium currents in rat CA1 hippocampal neurons. In the present whole-cell recording study we examined whether calcium currents in dentate granule cells are also under control of corticosteroids. In a first series of experiments, in which the calcium chelator BAPTA was added to the recording solution, the amplitude of calcium currents induced by a voltage step to -10 mV was found to be enhanced shortly (1 or 2 days) after adrenalectomy compared to sham operation.

Corticosteroid actions in the hippocampus.

Corticosteroid hormones can enter the brain and bind to two intracellular receptor types that regulate transcription of responsive genes: (i) the high affinity mineralocorticoid receptors and (ii) the glucocorticoid receptors with approximately 10-fold lower affinity. Although most cells in the brain predominantly express glucocorticoid receptors, principal cells in limbic structures such as the hippocampus often contain glucocorticoid as well as mineralocorticoid receptors. Recent electrophysiological studies have examined the consequences of transcriptional regulation via the two receptor types for information transfer in the hippocampus.

The Yin and Yang of nuclear receptors: symposium on nuclear receptors in brain, Oegstgeest, The Netherlands, 13-14 April 2000.

Novel aspects of nuclear receptors and their function in brain were discussed at a recent Symposium in Oegstgeest, The Netherlands. Presentations covered the diversity of these receptors, their target genes, proteins involved in transcriptional regulation, functional consequences of nuclear receptor activation and their relevance for human pathology. By elucidating the signalling pathway of nuclear receptors in brain, potential targets for therapeutic treatment of brain disorders can be identified.

Corticosteroid effects on serotonin responses in granule cells of the rat dentate gyrus.

Granule cells in the rat dentate gyrus contain mineralocorticoid and glucocorticoid receptors to which the adrenal hormone corticosterone binds with differential affinity. These cells also express various receptor-subtypes for serotonin (5-HT), including the 5-HT1A receptor which mediates a membrane hyperpolarization accompanied by a decrease in membrane resistance. Earlier studies have shown that removal of corticosterone by adrenalectomy, particularly in the dentate gyrus, results in enhanced expression of the 5-HT1A receptor mRNA and increased 5-HT1A receptor binding capacity.

Effect of adrenalectomy on membrane properties and synaptic potentials in rat dentate granule cells.

Adrenalectomy is known to accelerate both neurogenesis and cell death of granule cells located in the suprapyramidal blade of the rat dentate gyrus. Three days after adrenalectomy, some granule cells have already died by apoptosis while newly formed cells are not yet incorporated in the cell layer, resulting in a temporary loss of granule cells. Concomitantly, the field response to stimulation of perforant path afferents is reduced.

Modulatory actions of steroid hormones and neuropeptides on electrical activity in brain.

Electrophysiological studies over the past decades have shown that many compounds in addition to 'classical' neurotransmitters affect electrical activity in the brain. These compounds include neuropeptides synthesized in brain as well as compounds which are released from peripheral sources and subsequently enter the brain compartment, such as corticosteroid hormones from the adrenal gland. In the present review, this principle is illustrated by describing the effects of two substances, i.

Corticosteroid actions in hippocampus require DNA binding of glucocorticoid receptor homodimers.

Glucocorticoids are secreted from the adrenal gland in very high amounts after stress. In the brain, these stress hormones potently modulate ionic currents, monoaminergic transmission, synaptic plasticity and cellular viability, most notably in the hippocampus where corticosteroid receptors are highly enriched. Here we show that at least some of these actions require DNA binding of glucocorticoid receptor (GR) homodimers.

The corticosterone synthesis inhibitor metyrapone prevents hypoxia/ischemia-induced loss of synaptic function in the rat hippocampus.

Background And Purpose: Ischemia is accompanied by abundant corticosterone secretion, which could potentially exacerbate brain damage via activation of glucocorticoid receptors. We addressed whether manipulating steroid levels during ischemia affects hippocampal synaptic function along with neuronal structure. Moreover, we established whether pretreatment with the glucocorticoid receptor antagonist RU38486 is as effective in preventing deleterious effects after ischemia as is the steroid synthesis inhibitor metyrapone.

Field responses to perforant path stimulation in the rat dentate gyrus: role of corticosterone and NMDA-receptor activation.

Recent studies showed that corticosterone and NMDA receptor activation suppress cell turn-over in the dentate gyrus through a common pathway, the NMDA receptor acting downstream of the corticosteroids. The present data show that in the absence of corticosteroids but not of NMDA receptor activation synaptic responses of dentate cells are reduced. The reduced synaptic responsiveness in the absence of corticosterone is therefore probably not caused by changes in cell turn-over.

Effect of corticosteroid treatment in vitro on adrenalectomy-induced impairment of synaptic transmission in the rat dentate gyrus.

Removal of the rat adrenals results after 3 days in the appearance of apoptotic cells in the dentate gyrus. Apoptosis is accompanied by an impaired synaptic transmission in the dentate gyrus. Substitution in vivo with a low dose of corticosterone was found to prevent both the appearance of apoptotic cells and the functional impairment.