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C Cirelli

Publications and source records attributed to C Cirelli.

At least 37 records · Page 2Linked to original sources
PubMed1996

Neuronal gene expression in the waking state: a role for the locus coeruleus.

Several transcription factors are expressed at higher levels in the waking than in the sleeping brain. In experiments with rats, the locus coeruleus, a noradrenergic nucleus with diffuse projections, was found to regulate such expression. In brain regions depleted of noradrenergic innervation, amounts of c-Fos and nerve growth factor-induced A after waking were as low as after sleep. Phosphorylation of cyclic adenosine monophosphate response element-binding protein was also reduced. In contrast, electroencephalographic activity was unchanged. The reduced activity of locus coeruleus neurons may explain why the induction of certain transcription factors, with potential effects on plasticity and learning, does not occur during sleep.

Adrenergic Fibers↗
PubMed1996

Identification and characterization of a RING zinc finger gene (C-RZF) expressed in chicken embryo cells.

To identify changes in gene expression that occur in chicken embryo brain (CEB) cells as a consequence of their binding to the extracellular matrix molecule cytotactin/tenascin (CT/TN), a subtractive hybridization cloning strategy was employed. One of the cDNA clones identified was predicted to encode 381 amino acids and although it did not resemble any known sequences in the nucleic acid or protein data bases, it did contain the sequence motif for the cysteine-rich C3HC4 type of zinc finger, also known as a RING-finger. This sequence was therefore designated the chicken-RING zinc finger (C-RZF). In addition to the RING-finger, the C-RZF sequence also contained motifs for a leucine zipper, a nuclear localization signal, and a stretch of acidic amino acids similar to the activation domains of some transcription factors. Southern analysis suggested that C-RZF is encoded by a single gene. Northern and in situ hybridization analyses of E8 chicken embryo tissues indicated that expression of the C-RZF gene was restricted primarily to brain and heart. Western analysis of the nuclear and cytoplasmic fractions of chicken embryo heart cells and immunofluorescent staining of chicken embryo cardiocytes with anti-C-RZF antibodies demonstrated that the C-RZF protein was present in the nucleus. The data suggest that we have identified another member of the RING-finger family of proteins whose expression in CEB cells may be affected by CT/TN and whose nuclear localization and sequence motifs predict a DNA-binding function in the nucleus.

Amino Acid Sequence↗
PubMed1996

c-fos Expression in the rat brain after unilateral labyrinthectomy and its relation to the uncompensated and compensated stages.

The expression of the immediate early gene c-fos has been studied in the entire brain of rats 3, 6 and 24 h after surgical unilateral labyrinthectomy. We combined in situ hybridization for c-fos messenger RNA with immunocytochemistry for Fos protein to document very early changes in c-fos expression and to identify with cellular resolution neuronal populations activated by unilateral labyrinthectomy. Three hours after unilateral labyrinthectomy a bilateral increase in both c-fos messenger RNA and protein levels was seen in the superior, medial and spinal vestibular nuclei, nucleus Y, and prepositus hypoglossal nucleus. These changes were asymmetric in the medial vestibular nucleus, being most prominent in the dorsal part of the contralateral nucleus (where second order vestibular neurons are located) and in the ventral part of the ipsilateral nucleus (where commissural neurons acting on the medial vestibular nucleus of the intact side are located). An increase in c-fos messenger RNA expression was seen bilaterally, but with an ipsilateral predominance, in the vermal and paravermal areas of the cerebellar cortex, flocculus and paraflocculus, as well as in the precerebellar lateral and paramedian reticular nuclei. c-fos messenger RNA and protein levels increased in a few regions of the contralateral inferior olive. A predominantly ipsilateral increase in c-fos expression also occurred in the caudate-putamen. A bilateral but not exactly symmetric increase in both c-fos messenger RNA and protein levels was present in several nuclei of the dorsal pontine tegmentum (parabrachial nucleus, locus coeruleus and laterodorsal tegmental nucleus), mesencephalic periaqueductal gray, and several hypothalamic, thalamic and cerebrocortical regions. No change was seen in the cerebellar nuclei, lateral vestibular nucleus and red nucleus. The increased expression of c-fos observed 3 h after unilateral labyrinthectomy, in conjunction with the sudden occurrence of postural and motor deficits, usually declined 6-24 h after the lesion, i.e. during the development of vestibular compensation. In the dorsal part of the medial vestibular nucleus, however, the pattern of c-fos expression observed 3 h after unilateral labyrinthectomy was reversed 6-24 h after the lesion: both c-fos messenger RNA and protein levels increased on the ipsilateral side, but greatly decreased on the contralateral side. In conclusion, asymmetric changes in c-fos expression occurred within 3 h after unilateral labyrinthectomy, but gradually declined or reversed 6 and 24 h after the lesion, thus being temporally related to the appearance and development of vestibular compensation.

Animals↗
PubMed1995

Sleep-waking changes after c-fos antisense injections in the medial preoptic area.

The preoptic hypothalamus has been consistently implicated in the homeostatic regulation of sleep and waking. Recently, it was shown that periods of either spontaneous or forced wakefulness result in the induction in this region of the immediate-early gene c-fos. In this study, antisense oligonucleotides complementary to c-fos mRNA were employed to interfere with the expression of Fos protein. Injections in the rat medial preoptic area of c-fos antisense, but not of sense, oligonucleotides blocked the expression of Fos protein detected immunocytochemically. Rats receiving bilateral antisense injections showed a higher percentage of wakefulness the day after the injection than controls receiving sense or sham injections or antisense injections outside the preoptic area. These results suggest that blocking the expression of Fos protein in the preoptic hypothalamus may interfere with the homeostatic regulation of sleep and wakefulness.

Animals↗
PubMed1995

c-Fos expression during wakefulness and sleep.

We have recently demonstrated that c-fos expression is strongly induced by both spontaneous and forced wakefulness in many brain regions. c-Fos expression was considerably increased in regions involved in the regulation of arousal states, such as the locus coeruleus (noradrenergic neurons) and the medial preoptic area (non-GABAergic neurons). With c-fos antisense injection in the medial preoptic area, we demonstrated that c-fos expression in this region is causally involved in sleep regulation. c-Fos expression in other areas, such as the cerebral cortex and the hippocampus, may be related to the functional consequences of prolonged wakefulness and to the need of sleep. Further work should explore the mechanisms leading to changes in the expression of c-fos, and possibly of its target genes, during the sleep-wake cycle.

Animals↗
PubMed1995

Sleep deprivation and c-fos expression in the rat brain.

This study examined the effects of sleep deprivation on the expression of the immediate early gene c-fos in the brain with both in situ hybridization and immunocytochemistry. Rats were manually sleep-derived for 3 h, 6 h, 12 h, and 24 h starting at light onset (08.00 hours), and for 12 h starting at dark onset (20.00 hours). c-Fos expression was found to be higher in sleep-deprived rats with respect to control animals in several brain areas. The increase was evident both in terms of c-fos mRNA and Fos protein, although with a different time course. Among the areas that showed a consistent induction of c-fos were many cortical regions, the medial preoptic area and the posterior hypothalamic area, some thalamic nuclei, and several nuclei of the dorsal pontine tegmentum. The pattern of c-fos expression after sleep deprivation was very similar to that observed after comparable periods of spontaneous wakefulness (Pompeiano et al. 1994). In general, the increase in c-fos expression was not simply proportional to the amount of previous wakefulness. In many areas, the highest levels of c-fos were seen after 3 h of sleep deprivation. These observations are discussed with respect to the homeostatic regulation of sleep and to the functional consequences of wakefulness in specific brain areas.

Journal Article↗
PubMed1995

Changes in gene expression during the sleep-waking cycle: a new view of activating systems.

Moruzzi pioneered the notion of ascending activating systems that were responsible for the electrophysiological activation characterizing the transition from sleep to waking. This paper proposes to extend the notion of electrophysiological activation to the domain of gene expression. Evidence is reviewed indicating that in the transition between sleep and waking there is, together with a change in neuronal firing patterns, a change in patterns of gene expression in widespread regions of the brain. The hypothesis is presented that changes in the activity of neuromodulatory systems with diffuse projections may subserve the diffuse, tonic and phasic activation of both neuronal responses and of gene expression. Finally, the paper discusses the possibility that such changes in gene expression may be of importance for plastic phenomena and for the functional consequences of sleep.

Animals↗
PubMed1994

The locus coeruleus and immediate-early genes in spontaneous and forced wakefulness.

In this study, we mapped the expression of two immediate-early genes to examine the functional activation of the locus coeruleus and other regions of the rat brain after periods of spontaneous wakefulness or sleep and after sleep deprivation. c-fos and NGFI-A are two immediate-early genes that are rapidly induced by physiological stimuli and can be used as molecular markers of neural activation. We used immunocytochemical detection of Fos and NGFI-A proteins associated with double labeling for tyrosine hydroxylase to identify activated noradrenergic cells. We found that the expression of Fos and NGFI-A was markedly increased in the locus coeruleus and other brain areas both after spontaneous wakefulness and after short periods (3-24 h) of sleep deprivation. Several Fos-positive cells and most NGFI-A positive cells found in the locus coeruleus after periods of spontaneous wakefulness were shown to be noradrenergic. This study demonstrates that wakefulness per se, whether spontaneous or induced by total sleep deprivation, results in the functional activation of identified noradrenergic locus coeruleus cells.

Animals↗
PubMed1994

Immediate-early genes in spontaneous wakefulness and sleep: expression of c-fos and NGFI-A mRNA and protein.

We have recently shown that the expression of two immediate-early genes, c-fos and NGFI-A, is strongly affected by sleep deprivation, In this work, we investigated c-fos and NGFI-A expression after periods of spontaneous wakefulness or sleep. We used in situ hybridization and immunocytochemistry to detect the corresponding mRNA and protein levels, respectively. A first group of rats (S-L) was sacrificed during the light hours at the end of a long period of sleep. A second group (W-L) was sacrificed under similar conditions, except that during the last half hour the animals had been spontaneously awake. A third group (W-D) was sacrificed during the dark hours after a long period of continuous wakefulness. We found that c-fos and NGFI-A expression in several brain areas was increased in W-L and W-D rats with respect to S-L rats. Some of these areas, including the cerebral cortex, basal ganglia, and colliculi, may have been activated by the increased sensory and motor activity associated with waking. The activation of other areas, such as the medial preoptic area of the hypothalamus and some brainstem nuclei, may be more directly related to sleep regulation. These results indicate that many regions showing an increased expression of immediate early genes after wakefulness induced by sleep deprivation are also activated by periods of spontaneous wakefulness.

Journal Article↗
PubMed1993

Modulation of vestibulospinal reflexes through microinjection of an alpha 1-adrenergic antagonist in the dorsal pontine tegmentum of decerebrate cats.

1. The possibility that the norepinephrine (NE)-containing locus coeruleus (LC) neurons produce changes in posture as well as in gain of the vestibulospinal (VS) reflexes by acting on the dorsolateral pontine tegmentum (DPT) and the related medullary inhibitory reticulospinal (RS) system through alpha 1-adrenoceptors has been investigated in decerebrate cats. 2. Injection of the alpha 1-adrenergic antagonist prazosin PRZ (0.25 microliter at 0.1-1 microgram/microliter solvent) into the DPT, namely in the dorsal pontine reticular formation (pRF), as well as in the peribrachial nucleus of one side, decreased the postural activity in the ipsilateral limbs while increasing that of the contralateral limbs. In addition, the amplitude of modulation and thus the gain of the multiunit EMG responses of the ipsilateral and to a lesser extent of the contralateral triceps brachii to roll tilt of the animal at 0.15 Hz, +/- 10 degrees, increased. These effects appeared 5-10 min after the injection, reached the highest values in about 40-60 min and persisted for additional 1.5-2 h before disappearing. 3. The effects were site-specific and to some extent dose-dependent. However, neither changes in posture nor in gain of the VS reflexes were obtained after injection in the effective area of an equal volume of solvent. 4. In order to account for these findings it was postulated that the alpha 1-antagonist blocks the tonic inhibitory influence that the NE-containing LC neurons exert on ipsilateral DPT either by exciting through alpha 1-receptors interposed inhibitory interneurons, or by inhibiting presynaptically excitatory afferents to the same pontine tegmental structures. The increased discharge of these neurons and the related medullary inhibitory RS neurons would reduce the postural activity in the ipsilateral limbs. However, since the inhibitory RS neurons show a response pattern to tilt opposite in sign to that elicited by the excitatory VS neurons, we could expect that for a given labyrinth signal, the increased discharge of the RS neurons in the animal at rest would lead to a greater disinhibition of limb extensor motoneurons during ipsilateral tilt. These motoneurons would then respond more efficiently to the same excitatory volleys elicited by given parameters of stimulation, thus leading to an increased gain of the EMG responses of forelimb extensors to labyrinth stimulation. The possibility that the DPT of one side activates inhibitory RS neurons of both sides explains why PRZ increases the gain of the VS reflexes not only ipsilaterally but also contralaterally to the side of the injection.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1992

Modulation of desynchronized sleep through microinjection of alpha 1-adrenergic agonists and antagonists in the dorsal pontine tegmentum of the cat.

Noradrenaline is involved in the regulation of the sleep/waking cycle by acting through various receptor types. In previous studies we investigated the role of beta- and alpha 2-adrenergic receptors through local microinjections of various drugs into the dorsal pontine tegmentum (DPT) of the cat. This region is known to be crucially involved in desynchronized sleep execution. In this study we examined the role of alpha 1-adrenergic receptors. The alpha 1-agonist methoxamine and the alpha 1-antagonist prazosin were injected into the DPT of freely moving, unanaesthetized cats. We found that methoxamine notably reduced desynchronized sleep, and that this effect was both dose-dependent and site-specific. These effects were prevented by the subsequent injection of prazosin. On the other hand, the injection into the DPT of prazosin alone produced scarce or inconsistent effects on the sleep/waking cycle.

Animals↗
PubMed1992

Effects of sleep deprivation on fos-like immunoreactivity in the rat brain.

The molecular mechanisms involved in sleep regulation and function are largely unknown, and our understanding of the localization of such mechanisms within specific brain structures is still incomplete. In this work, we explored the consequences of sleep deprivation by the immunocytochemical mapping of the induction of the protein product of the immediate early gene c-fos in the brain of sleep-deprived rats. The expression of Fos protein is an indicator of neuronal activity. In addition, since immediate early genes can function as "third messengers" and regulate the transcription of a number of target genes, their induction could be directly relevant to the homeostasis and functions of sleep. The present results show that, as a result of 24 hours of manual sleep deprivation, Fos-like immunoreactive cells are found in specific brain areas. These areas include the medial preoptic area of the hypothalamus, the nucleus accumbens, the lateral septum, several regions of the dorsal pontine tegmentum (central gray, dorsal raphe, locus coeruleus, pedunculopontine and laterodorsal tegmental nuclei, parabrachial nuclei) and an area medial to the parabigeminal nucleus at the ponto-mesencephalic junction. Some of these areas had already been implicated in slow-wave sleep and desynchronized sleep regulation.

Animals↗
PubMed1991

Suppression of desynchronized sleep through microinjection of the alpha 2-adrenergic agonist clonidine in the dorsal pontine tegmentum of the cat.

The relationships between sleep-waking states and the activity of the noradrenergic system are controversial. In particular, according to an influential model of desynchronized sleep (DS) generation, the arrest of firing of noradrenergic neurons in the locus coeruleus should enhance DS, due to the release from inhibition of executive neurons located in the nearby pontine tegmentum. Since locus coeruleus neurons are strongly inhibited by alpha 2-adrenergic agonists like clonidine, this agent would be expected to increase DS. Yet clonidine powerfully decreases DS when injected systemically in several species. In this study, clonidine was microinjected locally into the dorsal pontine tegmentum of the cat, a region which comprises anatomically the whole locus coeruleus complex and which plays a key role in the generation of DS. In accord with the results of systemic experiments, bilateral injections of clonidine almost suppressed DS and unilateral injections consistently reduced it. The effects were dose dependent and site specific. It is suggested that clonidine may suppress DS by acting additionally on non-noradrenergic cell groups located in the dorsal pontine tegmentum.

Adrenergic alpha-Agonists↗