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C G Hatalski

Publications and source records attributed to C G Hatalski.

At least 19 recordsLinked to original sources
PubMed2001

Rapid phosphorylation of the CRE binding protein precedes stress-induced activation of the corticotropin releasing hormone gene in medial parvocellular hypothalamic neurons of the immature rat.

The mechanisms of the molecular and neuroendocrine responses to stress in the immature rat have been a focus of intense investigation. A principal regulator of the these responses in both mature and developing rat is the neuropeptide corticotropin releasing hormone (CRH), and levels of hypothalamic CRH mRNA are enhanced by stress. In vitro, transcription of the CRH gene is governed by binding of the phosphorylated form of cAMP responsive element binding protein (pCREB) to the promoter. Here we tested the hypothesis that rapid, stress-induced CRH transcription occurred during the first two postnatal weeks, and is associated with pCREB expression. The time-course of induction of unedited, heteronuclear CRH RNA (CRH hnRNA) was examined in hypothalamic paraventricular nucleus (PVN) of immature rats subjected to both modest and strong acute stressors using in situ hybridization; pCREB abundance was determined in individual neurons in specific PVN sub-nuclei using immunocytochemistry and unbiased quantitative analysis. CRH hnRNA signal was negligible in PVN of immature rats sacrificed under stress-free conditions, but was readily detectable within 2 min, and peaked at 15 min, in PVN of stressed animals. Enhanced pCREB immunoreactivity was evident within 2 min of stress onset, and was enhanced specifically in stress-responsive, CRH-expressing medial parvocellular neurons. These data support the notion that, already during early postnatal life, stress induces rapid CREB phosphorylation, interaction of pCREB-containing transcription complexes with the CRE element of the CRH gene promoter, and initiation of CRH hnRNA production in stress-responsive neurons of rat PVN.

Acute Disease↗
PubMed2001

Neurobiology of the stress response early in life: evolution of a concept and the role of corticotropin releasing hormone.

Over the last few decades, concepts regarding the presence of hormonal and molecular responses to stress during the first postnatal weeks in the rat and the role of the neuropeptide corticotropin releasing hormone (CRH) in these processes, have been evolving. CRH has been shown to contribute critically to molecular and neuroendocrine responses to stress during development. In turn the expression of this neuropeptide in both hypothalamus and amygdala is differentially modulated by single and recurrent stress, and is determined also by the type of stress (eg, psychological or physiological). A likely transcriptional regulatory factor for modulating CRH gene expression, the cAMP responsive element binding protein CREB, is phosphorylated (activated) in the developing hypothalamus within seconds of stress onset, preceding the transcription of the CRH gene and initiating the activation of stress-induced cellular and neuroendocrine cascades. Finally, early life stress may permanently modify the hypothalamic pituitary adrenal axis and the response to further stressful stimuli, and recent data suggest that CRH may play an integral role in the mechanisms of these long-term changes.

Animals↗
PubMed2000

Neuronal activity and stress differentially regulate hippocampal and hypothalamic corticotropin-releasing hormone expression in the immature rat.

Corticotropin-releasing hormone, a major neuromodulator of the neuroendocrine stress response, is expressed in the immature hippocampus, where it enhances glutamate receptor-mediated excitation of principal cells. Since the peptide influences hippocampal synaptic efficacy, its secretion from peptidergic interneuronal terminals may augment hippocampal-mediated functions such as learning and memory. However, whereas information regarding the regulation of corticotropin-releasing hormone's abundance in CNS regions involved with the neuroendocrine responses to stress has been forthcoming, the mechanisms regulating the peptide's levels in the hippocampus have not yet been determined. Here we tested the hypothesis that, in the immature rat hippocampus, neuronal stimulation, rather than neuroendocrine challenge, influences the peptide's expression. Messenger RNA levels of corticotropin-releasing hormone in hippocampal CA1, CA3 and the dentate gyrus, as well as in the hypothalamic paraventricular nucleus, were determined after cold, a physiological challenge that activates the hypothalamic pituitary adrenal system in immature rats, and after activation of hippocampal neurons by hyperthermia. These studies demonstrated that, while cold challenge enhanced corticotropin-releasing hormone messenger RNA levels in the hypothalamus, hippocampal expression of this neuropeptide was unchanged. Secondly, hyperthermia stimulated expression of hippocampal immediate-early genes, as well as of corticotropin-releasing hormone. Finally, the mechanism of hippocampal corticotropin-releasing hormone induction required neuronal stimulation and was abolished by barbiturate administration. Taken together, these results indicate that neuronal stimulation may regulate hippocampal corticotropin-releasing hormone expression in the immature rat, whereas the peptide's expression in the hypothalamus is influenced by neuroendocrine challenges.

Action Potentials↗
PubMed1999

Differential regulation of the expression of corticotropin-releasing factor receptor type 2 (CRF2) in hypothalamus and amygdala of the immature rat by sensory input and food intake.

The physiological consequences of activating corticotropin-releasing factor receptor type 2 (CRF2) are not fully understood. The neuroanatomic distribution of this CRF receptor family member is consistent with roles in mediating the actions of CRF and similar ligands on food intake control and integrative aspects of stress-related behaviors. However, CRF2 expression in the adult rat is not influenced by stress, corticosterone (CORT), or food intake. In immature rat we have demonstrated striking downregulation of CRF2mRNA in hypothalamic ventromedial nucleus (VMH) after 24 hr of maternal deprivation, a paradigm consisting of both physiological/psychological stress and food deprivation. The current study aimed to distinguish which element or elements of maternal deprivation govern CRF2mRNA expression by isolating the effects of food intake and discrete maternal sensory cues on CRF2mRNA levels in VMH and in reciprocally communicating amygdala nuclei. In maternally deprived pups, CRF2mRNA levels in VMH and basomedial (BMA) and medial (MEA) amygdala nuclei were 62, 72, and 102% of control levels, respectively. Sensory inputs of grooming and handling as well as of the pups' own suckling activity-but not food intake-fully restored CRF2mRNA expression in VMH. In contrast, all manipulations tended to increase CRF2mRNA levels in BMA of maternally deprived rats, and surrogate grooming increased CRF2mRNA expression significantly above that of nondeprived controls. CRF2mRNA expression was not influenced significantly by plasma adrenocorticotropic hormone (ACTH) and CORT levels. Thus, in the immature rat, (1) CRF2 expression is regulated differentially in hypothalamic and amygdala regions, and (2) CRF2mRNA levels in VMH are governed primarily by maternal or suckling-derived sensory input rather than food intake or peripheral stress hormones. These findings indicate a region-specific regulation of CRF2mRNA, supporting the participation of the receptor in neurochemically defined circuits integrating sensory cues to influence specific behavioral and visceral functions.

Adrenocorticotropic Hormone↗
PubMed1999

Differential regulation of glucocorticoid receptor messenger RNA (GR-mRNA) by maternal deprivation in immature rat hypothalamus and limbic regions.

Maternal deprivation (MDep) of neonatal rats significantly influences the hypothalamic-pituitary-adrenal (HPA) axis. This study hypothesized that GR-mRNA modulation constituted an early, critical mechanism for the acute effects of MDep on neuroendocrine stress-responses. GR-mRNA hybridization signal in hippocampal CA1, hypothalamic paraventricular nucleus (PVN) and frontal cortex was significantly reduced immediately following 24 h MDep. In amygdala, cingulate cortex, PVN and CA1, apparent gender-dependent MDep effects on GR-mRNA expression were observed, without significant differences in absolute levels. Thus, rapid, region-specific MDep effects on GR-mRNA expression in HPA-regulating areas are shown, consistent with involvement of GR-expression in mechanisms of MDep influence on HPA tone.

Aging↗
PubMed1999

Effects of blocking GABA degradation on corticotropin-releasing hormone gene expression in selected brain regions.

PURPOSE: The gamma-aminobutyric acid (GABA) degradation blocker gamma-vinyl-GABA (VGB) is used clinically to treat seizures in both adult and immature individuals. The mechanism by which VGB controls developmental seizures is not fully understood. Specifically, whether the anticonvulsant properties of VGB arise only from its elevation of brain GABA levels and the resulting activation of GABA receptors, or also from associated mechanisms, remains unresolved. Corticotropin-releasing hormone (CRH), a neuropeptide present in many brain regions involved in developmental seizures, is a known convulsant in the immature brain and has been implicated in some developmental seizures. In certain brain regions, it has been suggested that CRH synthesis and release may be regulated by GABA. Therefore we tested the hypothesis that VGB decreases CRH gene expression in the immature rat brain, consistent with the notion that VGB may decrease seizures also by reducing the levels of the convulsant molecule, CRH. METHODS: VGB was administered to immature, 9-day-old rats in clinically relevant doses, whereas littermate controls received vehicle. RESULTS: In situ hybridization histochemistry demonstrated a downregulation of CRH mRNA levels in the hypothalamic paraventricular nucleus but not in other limbic regions of VGB-treated pups compared with controls. In addition, VGB-treated pups had increased CRH peptide levels in the anterior hypothalamus, as shown by radioimmunoassay. CONCLUSIONS: These findings are consistent with a reduction of both CRH gene expression and secretion in the hypothalamus, but do not support an indirect anticonvulsant mechanism of VGB via downregulation of CRH levels in limbic structures. However, the data support a region-specific regulation of CRH gene expression by GABA.

4-Aminobutyrate Transaminase↗
PubMed1999

Effect of immune priming on Borna disease.

Borna disease virus (BDV) is a neurotropic virus with a broad host and geographic range. Lewis rats were immunized against BDV with a recombinant vaccinia virus expressing the BDV nucleoprotein and were later infected with BDV to evaluate protection against Borna disease (BD). Relative to animals that were not immunized, immunized animals had a decreased viral burden after challenge with infectious virus, more marked inflammation, and aggravated clinical disease. These data suggest that a more robust immune response in Borna disease can reduce viral load at the expense of increased morbidity.

Animals↗
PubMed1998

Humoral immunity in the central nervous system of Lewis rats infected with Borna disease virus.

The aim of this study was to investigate the humoral immune response to Borna disease (BD) virus in the brain of experimentally infected Lewis rats. Abundant IgG was detected in BD-rat brain with isotype variation throughout infection. IgG was locally produced as indicated by an intact blood-brain barrier, Ig kappa light chain mRNA-containing cells in brain and accumulation of virus-specific antibodies in cerebrospinal fluid. Treatment with BD-rat serum altered viral gene expression in persistently infected cultured rat glioblastoma cells. These data suggest that antibodies, produced in the brain, may influence viral gene expression.

Animals↗
PubMed1998

Evolution of the immune response in the central nervous system following infection with Borna disease virus.

Borna disease virus infection of Lewis rats results in an immune-mediated disease associated with transient meningoencephalitis and persistent viral infection. In the acute phase of disease, perivascular immune cell infiltrates consisted of CD4 + and CD8 + T cells, macrophages and NK cells with peak expression of mRNAs encoding the cytokines IL1alpha, IL2, IL6, TNFalpha, and IFNgamma. In the chronic phase of disease, numbers of NK cells, B cells and activated microglia increased in the brain parenchyma with peak expression of IL4 mRNA. These data were consistent with a switch from a Th1-like, cellular immune response to a Th2-like, humoral immune response.

Animals↗
PubMed1998

The developmental profile of the corticotropin releasing factor receptor (CRF2) in rat brain predicts distinct age-specific functions.

Corticotropin releasing factor (CRF) activates two known receptor types, CRF1, and CRF2. In the adult rat brain, CRF2 has a distinct distribution pattern, suggesting that it may mediate functions exclusive of CRF1. The goal of this study was to determine the age-dependent distribution of CRF2-messenger RNA (CRF2-mRNA) in the rat brain. Brains from rats sacrificed under stress-free conditions on fetal days (F) 15, 16, 17 and 19, and postnatal days 1, 3, 5, 7, 9, 12, 15, 25, 49, and 90 (adult) were analyzed using semiquantitative in situ hybridization histochemistry. The onset and distribution of CRF2-mRNA in the developing rat brain revealed important differences from the adult expression pattern: earliest expression of CRF2-mRNA was observed in the ventromedial hypothalamus (VMH) on F16. High levels of CRF2-mRNA were present in the fronto-parietal cortex in the fetal and early postnatal brain but not later. Conversely, no CRF2-mRNA was detectable in the ventroposterior (lateral and medial) thalamic nuclei prior to postnatal day 7. Distinct developmental profiles of CRF2-mRNA were also observed in the lateral septum, medial, basal and cortical amygdala nuclei, and in several hippocampal fields. In conclusion, CRF2 is expressed in the hypothalamus on F16, prior to the detection of CRF itself in the paraventricular nucleus. The differential levels and distributions of CRF2-mRNA in hypothalamic and limbic brain regions indicate a precise regulation of this receptor's expression during development, as shown for CRF1. Regulation of the levels of CRF2 may modulate the effects of CRF (and related ligands) on target neurons, consistent with differential maturation of the functions mediated by this receptor.

Aging↗
PubMed1998

Neuropeptide-mediated excitability: a key triggering mechanism for seizure generation in the developing brain.

Most human seizures occur early in life,consistent with established excitability-promoting features of the developing brain. Surprisingly, the majority of developmental seizures are not spontaneous but are provoked by injurious or stressful stimuli. What mechanisms mediate'triggering' of seizures and limit such reactive seizures to early postnatal life? Recent evidence implicates the excitatory neuropeptide, corticotropin-releasing hormone (CRH). Stress activates expression of the CRH gene in several limbic regions, and CRH-expressing neurons are strategically localized in the immature rat hippocampus, in which this neuropeptide increases the excitability of pyramidal cells in vitro. Indeed, in vivo, activation of CRH receptors--maximally expressed in hippocampus and amygdala during the developmental period which is characterized by peak susceptibility to 'provoked' convulsions--induces severe, age-dependent seizures. Thus, converging data indicate that activation of expression of CRH constitutes an important mechanism for generating developmentally regulated, triggered seizures, with considerable clinical relevance.

Animals↗
PubMed1998

Corticotropin releasing factor mRNA expression in the hypothalamic paraventricular nucleus and the central nucleus of the amygdala is modulated by repeated acute stress in the immature rat.

Age-appropriate acute stress, such as cold exposure, provokes the secretion of corticotropin releasing factor (CRF) from the hypothalamus, leading to a robust increase of plasma corticosterone in the immature rat. This activation of the hypothalamic-pituitary-adrenal system is accompanied by a stress-induced increase of steady-state CRF-mRNA expression in the hypothalamic paraventricular nucleus (PVN). In the current study, we analysed changes in CRF-mRNA expression in the PVN and the central nucleus of the amygdala (ACe) in the immature rat in response to a single episode of cold stress and three repeated exposures to this same stressor. CRF-mRNA expression in the PVN increased after a single, but not repeated exposures to cold stress, while repeated acute stress increased the content of the CRF peptide in the anterior hypothalamus. In the ACe, repeated episodes of cold stress resulted in increased expression of CRF-mRNA. These findings indicate a differential regulation of CRF gene expression in the PVN and ACe of the immature rat by single and repeated acute stress.

Acute Disease↗
PubMed1998

Corticotropin releasing hormone antagonist does not prevent adrenalectomy-induced apoptosis in the dentate gyrus of the rat hippocampus.

Adrenalectomy in the mature rat leads to death of granule cells in the dentate gyrus of the hippocampal formation. The mechanisms underlying this cell death have not been fully clarified: It has been considered that the granule cells require adrenal steroids for their survival, since corticosterone replacement prevents their death. However, adrenalectomy-induced loss of negative feedback also increases levels of corticotropin releasing hormone (CRH) in several limbic brain regions. CRH is known to induce neuronal death in hippocampal regions rich in CRH receptors. This study tested the hypothesis that adrenalectomy-induced granule cell death is mediated via the enhanced activation of CRH receptors. The extent of granule cell degeneration was compared among 4 groups of young adult male rats: Sham-adrenalectomy controls, adrenalectomized rats, adrenalectomized rats infused with a CRH antagonist from the onset of steroid deprivation to the time of sacrifice, and adrenalectomized rats infused with vehicle only. (9-41)-alpha-helical CRH was administered using an osmotic pump into the cerebral ventricles. Adrenalectomy led to robust granule cell degeneration, which was maximal in the suprapyramidal blade of the dentate gyrus. Infusion of the CRH antagonist in doses shown to block CRH actions on limbic neurons did not decrease the number of degenerating granule cells compared with the untreated or vehicle-infused adrenalectomized groups. Therefore, blocking the actions of CRH does not prevent adrenalectomy-induced granule cell death, consistent with a direct effect of corticoids on the survival of these neurons.

Adrenalectomy↗
PubMed1997

Biochemical and functional analysis of the Borna disease virus G protein.

The Borna disease virus (BDV) antigenome is comprised of five major open reading frames (ORFs). Products have been reported only for ORFs I, II, and III, encoding N (p40), P (p24/p23), and M (gp18), respectively. ORF IV predicts a 57-kDa protein with several potential glycosylation sites. Analysis of radiolabeled extracts from BDV-infected C6 cells and BHK-21 cells transfected with a Semliki Forest virus vector that contains ORF IV demonstrated the presence of a 94-kDa protein (G protein) which was sensitive to tunicamycin, endoglycosidase F/N-glycosidase, and endoglycosidase H but not to O-glycosidase. Sera from BDV-infected rats detected the G protein and had neutralization activity that was reduced following immunoadsorption with the G protein. Preincubation of cells with the G protein interfered with BDV infectivity. This effect was enhanced by treatment of the G protein with the exoglycosidase alpha-mannosidase and reduced after subsequent treatment with N-acetyl-beta-D-glucosaminidase. In concert these findings indicate that ORF IV encodes a 94-kDa N-linked glycoprotein with extensive high mannose- and/or hybrid-type oligosaccharide modifications. The presence of neutralization epitopes on the G protein and its capacity to interfere with infectivity suggest that the G protein is important for viral entry.

Animals↗
PubMed1997

Corticotropin releasing factor receptor type II (CRF2) messenger ribonucleic acid levels in the hypothalamic ventromedial nucleus of the infant rat are reduced by maternal deprivation.

The stress neurohormone corticotropin releasing factor (CRF) activates at least two receptor types. Expression of corticotropin releasing factor receptor type II (CRF2) has been demonstrated in the hypothalamic ventromedial nucleus (VMH) of the adult and developing rat, but the physiological functions of VMH-CRF2 have not been elucidated. The VMH has been documented as an important participant in the regulation of food intake and its interactions with the hypothalamic-pituitary-adrenal axis and circadian rhythms. Regulation of VMH-CRF2 may thus play a role in the interplay of physiological alterations in metabolic state with the neuroendocrine and anorexic effects of CRF. This study determined the regulation of CRF2-mRNA expression in infant rats by the physiological consequences of maternal deprivation, i.e., fasting and stress. Using in situ hybridization, maternally deprived pups had an average 62% reduction of VMH-CRF2-mRNA levels compared with stress-free controls. Maternal deprivation also resulted in elevated plasma corticosterone levels (3.8 +/- 0.3 vs. 1.3 +/- 0.1 microg/dl) and an average 5.7% body weight loss. This study demonstrates that maternal deprivation, via fasting and HPA activation, leads to a dramatic decrease of CRF2-mRNA levels in the VMH. These results are consistent with a role for CRF2 activation in mediating some of the complex interactions of CRF (or urocortin) with regulation of food intake in the developing rat.

Animals↗
PubMed1997

Stress-induced transcriptional regulation in the developing rat brain involves increased cyclic adenosine 3',5'-monophosphate-regulatory element binding activity.

The cAMP-regulatory element (CRE) binding protein (CREB) functions as a trans-acting regulator of genes containing the CRE sequence in their promoter. These include a number of critical genes, such as CRF, involved in the hypothalamic response to stressful stimuli in the adult. The ability of the developing rat (during the first 2 postnatal weeks) to mount the full complement of this stress response has been questioned. We have previously demonstrated the stress-induced up-regulation of the transcription of hypothalamic CRF during the second postnatal week in the rat. The focus of the current study was to explore the mechanism of transcriptional regulation in response to stress through the physiological induction of transcriptional trans-activators that bind to the CRE in the developing rat brain. CRE-binding activity was detected via gel shift analysis in extracts from both the hypothalamus and the cerebral cortex of the developing rat. CREB was identified in these extracts by Western blot analysis and was shown to be the major contributor to the CRE-binding activity by gel shift analysis with two specific antibodies directed against CREB. After acute hypothermic stress, the abundance of CRE-binding activity (but not of total immunoreactive CREB), increased in hypothalamic extracts. This enhanced CRE-binding activity was blocked by an antiserum directed against CREB and was accompanied by an apparent increase in CREB phosphorylation. These results indicate that posttranslational enhancement of CRE-binding activity is likely to constitute an important mechanism for up-regulation of genes possessing the CRE sequence in the developing rat hypothalamus by adverse external signals.

Animals↗
PubMed1995

Enzyme-linked immunosorbent assay for detecting antibodies to Borna disease virus-specific proteins.

Borna disease virus is a unique neurotropic RNA virus that causes neurologic disease in a wide variety of animal hosts. We established an enzyme-linked immunosorbent assay for the detection of antibodies to Borna disease virus on the basis of the use of three recombinant viral proteins (recp40, recp23, and recp18). This assay system is more sensitive and rapid than the methods currently used for the serologic diagnosis of infection such as Western blotting (immunoblotting), indirect immunofluorescence test, or immunoprecipitation.

Animals↗