Biomedical subjects

Elena Timofeeva

Publications and source records attributed to Elena Timofeeva.

12 recordsLinked to original sources

PubMed2006

Corticotropin-releasing factor and its receptors in the brain of rats with insulin and corticosterone deficits.

The expression of genes encoding corticotropin-releasing factor (CRF) and its receptor type-1 (CRF1R) and type-2alpha (CRF2R) has been studied in the brain of rats with streptozotocin (STZ)-induced diabetes and adrenalectomy (ADX). Diabetic rats had a lower body weight compared to control rats. Food and water intake were increased in diabetic rats and decreased in ADX animals. The plasma corticosterone levels measured at the nadir of the circadian rhythm were significantly higher in diabetic rats compared to non-diabetic animals. STZ-diabetic rats demonstrated an induction of expression of CRF mRNA in the magnocellular part of the paraventricular hypothalamic nucleus (PVN) and in the supraoptic nucleus (SON), whereas the CRF transcript in the parvocellular PVN was significantly lower in rats with insulin deficiency. ADX strongly triggered the expression of CRF mRNA in the parvocellular neurons of the PVN in both non-diabetic and diabetic rats, and it decreased magnocellular CRF mRNA in diabetic animals. The expression of the CRF1R in the parvocellular and magnocellular PVN and in the SON was induced by diabetes and decreased after ADX. The levels of the CRF2R mRNA in the ventromedial hypothalamic nucleus (VMH) were significantly lower in diabetic rats without any noticeable effects of ADX. The present results suggest opposite effects of insulin and corticosterone deficiency on the hypophysiotropic CRF and the CRF1R mRNA contents, whereas the expression of CRF2R was mostly related to insulin, but not to the corticosterone status.

Adipose Tissue↗

PubMed2006

Regulation of corticotropin-releasing factor and its types 1 and 2 receptors by leptin in rats subjected to treadmill running-induced stress.

The present study was conducted to investigate the long-term effects of subchronic elevation of central leptin levels on the expression of corticotropin-releasing factor (CRF) and its types 1 and 2 receptors in the brain of rats subjected to treadmill running-induced stress. PBS or recombinant murine leptin was infused continuously for a period of 5 days into the third ventricle of rats with the aid of osmotic minipumps at a delivery rate of 2 mug/day. On the fifth day of infusion, rats were killed under resting conditions or after a session of treadmill running, which is known to induce a stress response in rats. Leptin treatment significantly decreased food intake, body weight, white adipose tissue weight, glucose and insulin plasma contents, and blunted the treadmill running-induced elevation in plasma levels of corticosterone. Leptin infusion prevented stress-induced de novo synthesis of CRF in the paraventricular hypothalamic nucleus (PVN), which was measured using the intronic probe for CRF heteronuclear RNA. The induction of the type 1 CRF receptor (CRF(1)R) in the PVN and supraoptic nucleus in running rats was also significantly blunted by leptin. In contrast, leptin treatment strongly increased the expression of type 2 CRF receptor (CRF(2)R) in the ventromedial hypothalamic nucleus (VMH). The present results suggest that subchronic elevation of central levels of leptin blunts treadmill running-induced activation of the hypothalamic-pituitary-adrenal axis through the inhibition of activation of the CRFergic PVN neurons, and potentially enhances the anorectic CRF effects via the stimulation of expression of CRF(2)R in the VMH.

Adipose Tissue↗

PubMed2005

Cholinergic modulation of vibrissal receptive fields in trigeminal nuclei.

In sensory systems, it is usually considered that mesopontine cholinergic neurons exert their modulatory action in the thalamus by enhancing the relay of sensory messages during states of neural network desynchronization. Here, we report a projection heretofore unknown of these cholinergic cells to the interpolar division of the brainstem trigeminal complex in rats. After FluoroGold injection in the interpolar nucleus, a number of retrogradely labeled cells were found bilaterally in the pedunculopontine tegmental nucleus, and immunostaining revealed that the vast majority of these cells were also positive for choline acetyltransferase. Immunostaining for the acetylcholine vesicular transporter confirmed the presence of cholinergic terminals in the interpolar nucleus, where electron microscopy showed that they make symmetric and asymmetric synaptic contacts with dendrites and axon terminals. In agreement with these anatomical data, recordings in slices showed that the cholinergic agonist carbachol depolarizes large-sized interpolaris cells and increases their excitability. Local application of carbachol in vivo enhances responses to adjacent whiskers, whereas systemic administration of the cholinergic antagonist scopolamine produces an opposite effect. Together, these results show that mesopontine cholinergic neurons exert a direct, effective control over receptive field size at the very first relay stations of the vibrissal system in rodents. As far as receptive field synthesis in the lemniscal pathway relies on intersubnuclear projections from the spinal complex, it follows that cholinergic modulation of sensory transmission in the interpolar nucleus will have a direct bearing on the type of messages that is forwarded to the thalamus and cerebral cortex.

Acetylcholine↗

PubMed2005

The vibrissal system as a model of thalamic operations.

The highly segregated organization of the vibrissal system of rodents offers a unique opportunity to address key issues about thalamic operations in primary sensory and second order thalamic nuclei. In this short review, evidence showing that reticular thalamic neurons and relay cells with receptive fields on the same vibrissa form topographically closed loop connections has been summarized. Within whisker-related thalamic modules, termed barreloids, reticular axons synapse onto the cell bodies and dendrites of residing neurons as well as onto the distal dendrites of neurons that are located in adjacent barreloids. This arrangement provides a substrate for a mechanism of lateral inhibition whereby the spread of dendritic trees among surrounding barreloids determines whisker-specific patterns of lateral inhibition. The relay of sensory inputs in the posterior group, a second order nucleus associated with the vibrissal system is also examined. It is shown that in lightly anesthetized rats posterior group cells are tonically inhibited by GABAergic neurons of the ventral division of zona incerta. These observations suggest that a mechanism of disinhibition controls transmission of sensory signals in the posterior group nucleus. We further propose that disinhibition operates in a top-down manner, via motor instructions sent by cortex to brainstem and spinal cord. In this way posterior group nucleus would forward to the cerebral cortex sensory information that is contingent upon its action.

Afferent Pathways↗

PubMed2005

Contribution of the vagus nerve and lamina terminalis to brain activation induced by refeeding.

Following refeeding, c-fos expression is induced in a particular set of brain regions that include the nucleus of the solitary tract (NTS), parabrachial nucleus (PB), central amygdala (CeA), paraventricular hypothalamic nucleus (PVH), supraoptic nucleus (SON) and the circumventricular organs. Within the PVH, the expression is particularly intense in the magnocellular division of the nucleus and it is as yet not clear how this activation occurs. The respective contribution of the vagus afferents and lamina terminalis, which conveys signals entering the brain through the forebrain circumventricular organs, has been investigated in rats subjected to a unilateral cervical vagotomy (UCV) or a unilateral lesion of the fibres running within the lamina terminalis (ULT) and projecting to the neuroendocrine hypothalamus. UCV significantly decreased postprandial c-fos expression in the NTS, PB, CeA and parvocellular division of the PVH. In contrast, ULT impaired postprandial activation of the magnocellular neurons in the PVH and SON. The present study also characterized the types of neurons activated in the PVH and SON during refeeding. In the magnocellular regions, arginine-vasopressin (AVP) neurons were activated upon refeeding whereas there was no apparent induction of Fos expression in oxytocin cells. In the parvocellular PVH, postprandial Fos was induced only in 30% of the corticotrophin-releasing factor (CRF) and AVP neurons. The results of the present study suggest that the postprandial activation of the brain requires the integrity of both the vagal- and lamina terminalis-associated pathways.

Animals↗

PubMed2004

Corticosterone-dependent metabolic and neuroendocrine abnormalities in obese Zucker rats in relation to feeding.

The obese Zucker (fa/fa) rat is characterized by hyperphagia, hyperinsulinemia, an increase in fat deposition, and a hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis in fa/fa rats is hypersensitive to stressful experimental conditions. Food deprivation even leads to a stress reaction in obese fa/fa rats. The present study was conducted to investigate the role of corticosterone in obese rats on the basal, fasting, and postprandial metabolic rate as well as on the central expression of the thyrotropin-releasing hormone (TRH) in these conditions. In addition, the study was aimed at clarifying whether the high levels of corticosterone in obese rats are responsible for the induction of the stress reaction to food deprivation in these animals. The present results demonstrate that whole body fat oxidation and postprandial metabolic responses in obese Zucker rats were improved by adrenalectomy (ADX). At the level of the central nervous system, ADX reversed a decrease in TRH mRNA expression in the paraventricular hypothalamus (PVH) detected in fasting animals. Considering all feeding conditions, the obese rats demonstrated lower TRH mRNA levels compared with lean animals. ADX resulted in an enhanced postprandial activation of the parvocellular PVH. In contrast, the magnocellular part of the PVH was less responsive to refeeding in ADX animals. Finally, ADX failed to prevent the stress response of obese rats to food deprivation. The present results provide evidence that the removal of adrenals resolve some of the metabolic defects encountered in obese Zucker rats. They also demonstrate that not all the abnormalities of the obese Zucker rats are attributable to the hyperactivity of the HPA axis.

Animals↗

PubMed2003

Synthesis of multiwhisker-receptive fields in subcortical stations of the vibrissa system.

This study addresses the origins of multiwhisker-receptive fields of neurons in the thalamic ventral posterior medial (VPM) nucleus of the rat. We sought to determine whether multiwhisker-receptive field synthesis occurs in VPM through convergent projections from the principalis (PrV) and interpolaris (SpVi) nuclei, or in PrV by intersubnuclear projections from the spinal trigeminal complex. We tested these hypotheses by recording whisker-evoked responses in PrV and VPM before and after electrolytic lesion of the SpVi in lightly anesthetized rats. Before the lesion PrV cells responded, on average, to 3.2 +/- 1.2 whiskers but responsiveness was reduced to 1.07 +/- 0.31 whisker after the lesion. A similar reduction of receptive field size was observed in VPM, where neurons responded, on average, to 2.94 +/- 0.95 whiskers before the lesion and to 1.05 +/- 0.22 whisker after the lesion. Thus one can conclude that intersubnuclear projections mediate surround whisker-receptive fields in PrV, and therefore in VPM. However, it has previously been shown that parasagittal brain stem transection, which severed ascending projections from SpVi, but left intersubnuclear connections intact, rendered VPM cells monowhisker responsive. We wondered whether midline brain stem lesion modified receptive field properties in SpVi. In normal rats SpVi cells responded, on average, to 7.52 +/- 4.25 whiskers, but responsiveness was dramatically reduced to 1.47 +/- 1.07 whisker after the lesion. Together these results indicate that the synthesis of surround receptive fields in subcortical stations relies almost exclusively on intersubnuclear projections from the spinal trigeminal complex to the PrV.

Animals↗

PubMed2003

A map of angular tuning preference in thalamic barreloids.

A double-labeling protocol was used to determine how cells with different angular preferences to whisker motion distribute across the dimensions of a barreloid in the ventral posterior medial nucleus of the rat thalamus. Individual barreloids were labeled retrogradely by injecting Fluoro-Gold in identified barrel columns, and single relay cells (n = 30) pertaining to the labeled barreloids were stained juxtacellularly with Neurobiotin after determination of their angular tuning preference to controlled whisker deflection. Results show that cells with like angular preference are clustered within the barreloids. Those best tuned to forward and upward directions are located principally in the dorsal sector of the barreloid, whereas those best tuned to backward and downward motion are located principally in the central and ventral sectors, respectively. The relationship between cell location and angular preference was assessed by regression, cluster, and discriminant analysis. Together, these tests indicate that barreloids contain a map of shifting angular preference that transposes along the length of a barreloid directional property imposed at the periphery by the circumferential distribution of receptors around the vibrissa follicles.

Action Potentials↗

PubMed2003

The relay of high-frequency sensory signals in the Whisker-to-barreloid pathway.

The present study investigated the operational features of whisker-evoked EPSPs in barreloid cells and the ability of the whisker-to-barreloid pathway to relay high rates of whisker deflection in lightly anesthetized rats. Results show that lemniscal EPSPs are single-fiber events with fast rise times (<500 microsec) that strongly depress at short inter-EPSP intervals. They occur at short latencies (3.84 +/- 0.96 msec) with little jitters (<300 microsec) after electrical stimulation of the whisker follicle. Waveform analysis indicates that one to three lemniscal axons converge on individual barreloid cells to produce EPSPs of similar rise times but different amplitudes. When challenged by high rates of whisker deflection, cells in the whisker-to-barreloid pathway demonstrate a remarkable frequency-following ability. Primary vibrissa afferents could follow in a phase-locked manner trains of sinusoidal deflections at up to 1 kHz. Although trigeminothalamic cells could still faithfully follow deflection rates of 200-300 Hz, the actual frequency-following ability of individual cells depends on the amplitude, velocity, and direction of displacements. The discharges of trigeminothalamic cells induce corresponding phase-locked EPSPs in barreloid cells, which trigger burst discharges at stimulus onset. During the following cycles of the stimulus train, few action potentials ensue because of the strong synaptic depression at lemniscal synapses. It is concluded that the whisker-to-barreloid pathway can relay vibratory inputs with a high degree of temporal precision, but that the relay of this information to the cerebral cortex requires the action of modulators, and possibly phase-locked discharges among an ensemble of relay cells.

Animals↗

PubMed2003

Effects of treadmill running on brain activation and the corticotropin-releasing hormone system.

The present study was conducted to investigate the effects of treadmill running on the corticotropin-releasing hormone (CRH), CRH receptor type 1 (CRH-R1) and CRH-binding protein (CRH-BP) in the brain of rats that were killed either at rest, immediately after 60 min of treadmill running, or 180 min following a 60-min session of intensive exercise. The expression of the neuronal activity marker c-FOS was also determined in the three conditions of this study. The levels of c-FOS mRNA immediately following running were high in the cortex, caudate-putamen, lateral septum, bed nucleus of the stria terminalis, dorsal and medial thalamus, hypothalamus, pontine nuclei, locus coeruleus and hypoglossal nucleus. In most brain regions investigated, excluding the locus coeruleus and the cingulate cortex, c-FOS mRNA expression returned to control levels after 2 h of recovery. The highest concentration of cells co-expressing the protein Fos and CRH mRNA neurons was found in the parvocellular part of the paraventricular nucleus, which also expressed CRH heteronuclear RNA and CRH-R1 mRNA. The medial preoptic area (MPOA), the medial mammillary nucleus and the posterior hypothalamic as well as the somatosensory cortex, the medial geniculate nucleus, the reticulotegmental nucleus, and Barrington's nucleus also co-expressed Fos and CRH mRNA. The expression of CRH-BP gene was induced in the MPOA following running. In summary, the present study demonstrates that treadmill running leads to a strong expression of c-FOS mRNA that is widely distributed throughout the brain. c-FOS mRNA was found in structures of the somatosensory and somatomotor systems, indicating that these regions were activated during exercise. The pattern of distribution of c-FOS mRNA showed similarities with that triggered by neurogenic and systemic stresses. The present results also indicate that treadmill running can strongly activate the hypophysiotropic CRH system, which suggests, in agreement with the pattern of c-FOS mRNA distribution, that treadmill running has a strong stress component.

Animals↗

PubMed2002

The corticotropin-releasing factor family of peptides and CRF receptors: their roles in the regulation of energy balance.

The corticotropin-releasing factor (CRF) system could play a significant role in the regulation of energy balance. This system, which includes CRF, CRF-related peptides and CRF receptors, is part of a huge network of cells connected to central and peripheral pathways modulating energy metabolism. CRF and CRF-related peptides, which elicit their effects through G-protein-coupled receptors known in mammals as CRF(1) receptor and CRF(2) receptor, are capable of strong anorectic and thermogenic effects. Also supporting a role for the CRF system in the regulation of energy balance are findings demonstrating alterations in this system in obese and food-deprived animals that concur to facilitate energy deposition. In recent years, great progress has been made in understanding the specific physiological roles of the CRF system. In that respect, the discovery of urocortins II and III, two endogenous ligands of the CRF(2) receptor, and the development of selective and long-acting antagonists for the CRF receptors, have led to a better comprehension of the role of the CRF system in the regulation of energy balance. Although there are still important unresolved issues in the field of CRF research, the progress made recently warrants investigations aimed at evaluating the CRF system as a potential target for anti-obesity drugs.

Animals↗

PubMed2002

Neuronal activation and corticotropin-releasing hormone expression in the brain of obese (fa/fa) and lean (fa/?) Zucker rats in response to refeeding.

The present study was conducted to investigate the pattern of neuronal activation and corticotropin-releasing hormone (CRH) expression in fed, food deprived and refed lean (Fa/?) and obese (fa/fa) Zucker rats. The pattern of neuronal activation was studied by measuring the expression of the immediate-early gene c-fos. Expression of c-fos and CRH mRNA was determined by in situ hybridization histochemistry. In both lean and obese rats, one hour of refeeding led to a transient increase in c-fos mRNA levels which was detected in the paraventricular hypothalamic nucleus (PVH), the dorsomedial hypothalamic nucleus, the supraoptic nucleus, the paraventricular thalamic nucleus, the central nucleus of amygdala (CeA), the lateral and medial parabrachial nuclei, the nucleus of the solitary tract, and the area postrema. In addition, refeeding led to strong activation of the arginine-vasopressin neurons located in the magnocellular part of the PVH. Following 24 h of food deprivation, CRH expression in the parvocellular division of the PVH was significantly higher in obese rats compared to lean animals. During refeeding, PVH CRH mRNA levels in obese rats decreased to reach control values. The decrease in CRH expression in obese rats was accompanied by the alleviation of the hypercorticosteronemia that characterized obese Zucker rats. CRH mRNA levels in the central nucleus of the amygdala were significantly higher in lean rats than in obese animals, when the rats were fed ad libitum During food deprivation, CeA CRH mRNA levels decreased in lean rats and gradually returned to predeprivation values during refeeding. In refed obese rats, CeA levels of CRH mRNA were higher than those of ad libitum fed or food-deprived obese mutants. In the perifornical region of the lateral hypothalamic area (LHA), the expression of CRH mRNA rose significantly in response to refeeding in lean rats, but not in obese animals. Following the first hour of refeeding, the number of neurons expressing CRH mRNA in the LHA in lean rats almost doubled. The present results demonstrate that refeeding has a stimulating effect in obese Zucker rats in a pattern of activation similar to that seen in lean Fa/? rats. They also demonstrate differences in CRH expression between Fa/? and fa/fa rats after refeeding. The most apparent of these differences was seen in the lateral hypothalamus in which refeeding failed to up-regulate CRH expression in obese rats.

Animals↗